AdvAnces learning objectives SATURDAY, FEBRUARY 22, 2014
Advances learning in pharmacy practicE objectives Presented by: The CU Skaggs School of Pharmacy and Pharmaceutical Sciences SATURDAY, FEBRUARY 22, 2014 Program Schedule Advances in Pharmacy Practice: 2014 February 22, 2014 7:30 AM Sign‐in and Continental Breakfast 8:00 AM Announcements and Introductions 8:15 AM Immunizations 2014: What Pharmacists Can Do to Reduce Vaccinepreventable Disease Wesley Nuffer, PharmD, CDE 9:15 AM 10:15 AM 10:30 AM 11:30 AM 12:30 PM 1:30 PM 2:30 PM 3:15 PM 3:30 PM 4:30 PM Infectious Disease Update: Trends in Antimicrobial Resistance, Stewardship and Drug Development Gerard Barber, RPh, MPH, FASHP Refreshment Break Update on Current Medical Therapy for Diabetes Michael McDermott, MD Improving Outcomes from Pre-diabetes to Diabetes: Strategies to Minimize Progression and Complications Sam Ellis, PharmD, BCPS, CDE Lunch 2014 Regulatory and Legislative Update: State and National Perspectives Val Kalnins, RPh Drug Interactions Every Pharmacist Should Know Daniel Malone, RPh, PhD Break Evidence-based Treatment of Hypertension and High Blood Cholesterol: Update on New Guidelines Joseph Saseen, PharmD, FCCP, BCPS, CLS Program Evaluation and Wrap‐up Learning Objectives After attending each of the following presentations, participants should be able to: Immunizations 2014: What Pharmacists Can Do to Reduce Vaccine-preventable Disease ACPE# 0008‐0000‐14‐001‐L01‐P (1 contact hour – knowledge‐based) 1. Explain how vaccines and adjuvants stimulate the immune response and use this knowledge to recommend an appropriate immunization for a patient. 2. Describe the latest developments for the influenza vaccine (trivalent vs. quadrivalent, high‐dose, and different delivery systems) and outline vaccinations in the development pipeline. 3. List three steps that pharmacists can take to reduce the incidence of vaccine‐preventable diseases in their communities. Infectious Disease Update: Trends in Antimicrobial Resistance, Stewardship and Drug Development ACPE# 0008‐0000‐14‐002‐L01‐P (1 contact hour – knowledge‐based) 1. Describe the interplay of pathogen, host, and environment in the development of infectious disease and cite a recent example in which these elements were significant. 2. Citing at least one property of each, distinguish antimicrobial resistance from pathogen virulence. 3. Outline the purpose and multidisciplinary structure of an antimicrobial stewardship program and explain how pharmacists in outpatient and inpatient settings can promote appropriate antimicrobial usage. 4. Describe the potential indications and pharmacologic attributes of new antimicrobials currently in late‐stage development. Update on Current Medical Therapy for Diabetes ACPE# 0008‐0000‐14‐003‐L01‐P (1 contact hour – knowledge‐based) 1. Explain the pathophysiology that underlies current therapies for type 1 and type 2 diabetes mellitus. 2. Given a patient case, describe how to individualize A1C targets and drug choices for that person. 3. Discuss practical aspects of initiating and adjusting old and new therapeutic agents for diabetes mellitus. Learning Objectives – continued Improving Outcomes from Pre-diabetes to Diabetes: Strategies to Minimize Progression and Complications ACPE# 0008‐0000‐14‐004‐L01‐P (1 contact hour – knowledge‐based) 1. Outline the current evidence for the effectiveness of lifestyle interventions for the prevention or delay of progression to diabetes in patients who are at risk for diabetes. 2. Describe the non‐pharmacotherapeutic options to improve glucose control and reduce complications in patients with diabetes. 3. Given a profile of a patient with diabetes, provide two to three methods that a pharmacist could use to support the patient’s efforts to improve glucose control and subsequent diabetes complications. 2014 Regulatory and Legislative Update: State and National Perspectives ACPE# 0008‐0000‐14‐005‐L03‐P (1 contact hour – knowledge‐based) 1. Discuss the latest developments concerning the Affordable Care Act and how they will affect the practice of Pharmacy. 2. Summarize the latest developments in state and national initiatives and legislation related to pharmacy. 3. Describe the impact of FDA, DEA, and state board of pharmacy rules and proposed rules of 2012‐ 2013. Drug Interactions Every Pharmacist Should Know ACPE# 0008‐0000‐14‐006‐L01‐P (1 contact hour – knowledge‐based) 1. Describe the basic mechanisms for drug‐drug interactions. 2. Identify medications involved in clinically relevant interactions. 3. Given selected drug‐drug interactions, determine possible management strategies to minimize or avoid harm. Evidence-based Treatment of Hypertension and High Blood Cholesterol: Update on New Guidelines ACPE# 0008‐0000‐14‐007‐L01‐P (1 contact hour – knowledge‐based) 1. Describe the process for developing new hypertension, high blood cholesterol, and assessment of cardiovascular risk guidelines. 2. Review new guideline recommendations for the treatment of patients with hypertension and dyslipidemia. 3. List patient specific blood pressure goals and recommended treatments for patients with hypertension. 4. Identify patients who are eligible for statin‐based therapy and describe how they should be treated. Faculty Conference Coordinators Kathleen McCartney, PharmD Coordinator, Continuing Pharmacy Education University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Tonya Cook, PharmD, Clinical Pharmacy Specialist St. Mary’s Hospital Grand Junction, Colorado Brian Feagans, MS, RPh Pharmacy Clinical Manager St. Mary‐Corwin Hospital Pueblo, Colorado Brandi Koepp, PharmD, BCPS Pharmacy Clinical Coordinator Medical Center of the Rockies Loveland, Colorado Benton Westergaard Program Administrator, Continuing Pharmacy Education University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Faculty – continued Presenters Gerard Barber, RPh, MPH, FASHP Coordinator P&T and Clinical Pharmacy Services, Co‐Chair, Pharmacy & Therapeutics Committee University of Colorado Hospital Samuel Ellis, PharmD, BCPS, CDE Associate Professor Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Denver Val Kalnins, RPh Executive Director Colorado Pharmacists Society Daniel Malone, RPh, PhD Professor College of Pharmacy University of Arizona Michael McDermott, MD Director Endocrinology and Diabetes Practice University of Colorado Hospital Wesley Nuffer, PharmD, CDE Assistant Professor Skaggs School of Pharmacy and Pharmaceutical sciences Joseph Saseen, PharmD, FCCP, BCPS, CLS Professor and Vice Chair Department of Clinical Pharmacy Professor, Department of Family Medicine CU schools of Pharmacy and Medicine Immunizations 2014: What Pharmacists Can Do to Reduce Vaccine-preventable Disease ACPE # 0008-0000-14-001-L01-P (1 contact hour – knowledge based) Wesley Nuffer, PharmD, CDE Assistant Professor Department of Clinical Pharmacy CU Skaggs School of Pharmacy and Pharmaceutical sciences Learning Objectives 1. Explain how vaccines and adjuvants stimulate the immune response and use this knowledge to recommend an appropriate immunization for a patient. 2. Describe the latest developments for the influenza vaccine (trivalent vs. quadrivalent, high-dose, and different delivery systems)and outline vaccinations in the development pipeline. 3. List three steps that pharmacists can take to reduce the incidence of vaccine-preventable diseases in their communities. 2/10/2014 Learning Objectives • Explain how vaccines stimulate the immune response depending on vaccine type (live, inactivated, polysaccharide or conjugated) and use this knowledge to recommend an appropriate immunization for a patient Immunizations 2014: What pharmacists can do to reduce vaccine‐preventable disease Wesley Nuffer, PharmD, BCPS, CDE February 22nd, 2014 Vaccine‐Mediated Immunity http://www.historyofvaccines.org/content/how-vaccines-work • Describe the latest developments for the influenza vaccine (trivalent vs. quadrivalent, high‐dose, and different delivery systems) and outline vaccinations in the development pipeline. • List 3 steps that pharmacists can take to reduce the incidence of vaccine‐preventable diseases in their communities Response to Disease http://www.historyofvaccines.org/content/how-vaccines-work 1 2/10/2014 Polysaccharide Vaccines • Stimulate B cells but not T cells – “T‐cell independent” – Less immunologic memory – Lose “booster” effect • Ineffective in immature immune system – Children under 2 need conjugate • Link to protein (tetanus, diptheria) to enhance immunity • Now T cell immunity stimulated Inactive and Live Vaccines • Inactive vaccines won’t cause illness! – Do not reproduce – Utilize inert proteins/portions of the pathogen – May administer inactive vaccines together Diptheria • Live vaccines must reproduce to cause immunity – Delay in immune response – Theoretical risk to immunocompromised patients – Dosing intervals may be relevant • Can give two live vaccines simultaneously • If not administered together, need to wait 28 days Measles Live vs Inactive Vaccines Inactive Vaccines Live Vaccines - Live attenuated influenza (LAIV) - Herpes zoster - Varicella - Measles, mumps, rubella - Rotavirus - Yellow fever - Oral typhoid Influenza Vaccine - Inactivated influenza Pneumococcal Tdap & DTap Hepatitis A Hepatitis B Human papillomavirus (HPV) Inactive poliovirus Meningococcal Haemophilus influenzae Rabies Typhoid injection 1918 Influenza fears 2 2/10/2014 2013‐2014 Influenza Vaccine • A/California/7/2009 (H1N1) pdm09‐like virus • A (H3N2) virus antigenically like the cell‐propagated prototype virus A/Victoria/361/2011 • B/Massachusetts/2/2012‐like virus • B/Brisbane/60/2008‐like virus (Quadrivalent only) 2014 Influenza Season Influenza Vaccine without Eggs • Development – Isolation of the hemagglutinin (HA) protein – No egg embryo or thimerosol used in production – Contains HA protein of all three strains used for production • Flublok – Tri‐valent vaccine – Approved in adults 18‐49 years old – Shorter expiration date • 16 weeks from the date of production • Watch expiration date before administering 3 2/10/2014 High‐Dose Influenza Vaccine • Provides same trivalent protection with 4x antigen load • Indicated for people ≥ 65 years old – Clinical studies demonstrate stronger antibody response – No data yet to show the vaccine leads to better illness protection – On‐going study should answer effectiveness question in 2014‐15 • Higher adverse effects with high‐dose vaccine – Local site reactions – Headaches and fever – Muscle aches Alternate Delivery Routes & Devices Alternative Vaccine Delivery Systems • Intradermal devices – Intradermal needles – Needleless jet systems • Oral delivery via encapsulation/stabilization • Pulmonary delivery – Dry powder inhalers – Nebulizers – Intranasal delivery • Micro needle delivery “Jet” System Vaccine Delivery • Intradermal administration – Delivers vaccine into the skin, rather than into muscle • Smaller needle for delivery • Less antigen required in preparation for similar efficacy • Needleless “jet” systems 4 2/10/2014 Micro‐Needle Patch Delivery Vaccines Under Development • • • • • • • • • • • HIV Tuberculosis Salmonella Hepatitis C E Coli Bioterrorism agents (anthrax, smallpox, ricin) Epstein‐Barr Malaria Rabies Streptococci group A & B Cytomegalovirus Nat Biotechnol 31, 1082-1085, 2013 Pharmacist’s Role: Beyond Influenza? How many of you currently provide: – S. Pneumoniae (Pneumovax)? – Herpes Zoster (Zostavax)? – Hepatitis B? – TdaP/Td? – HPV? – Meningococcal? Pharmacist’s Role: Advocacy Vaccine (Recommended population) Vaccination rate (%) Influenza (Age 50‐64) 44.5% Influenza (Age >65) 66.6% Influenza (HCP) 63.4% Pneumococcal (High risk pts) 18.5% Pneumococcal (Age >65) 59.7% Tetanus in the past 5 years 52.3% Hepatitis B 42.0% Hepatitis B (HCP) 63.2% Zoster (Age >60) 14.4% National Health Interview Survey JAMA 3/2012 http://www.cdc.gov/flu/professionals/vaccination/vaccinecoverage.htm 5 2/10/2014 Pharmacist’s Role: Advocacy Race/Ethnicity Influenza (%) Pneumococcal (%) Hispanic 41.9% 39.0% Black 56.1% 46.2% White 67.7% 63.5% Pharmacist’s Role: Education • CDC resources – MMWR listserv: www.cdc.gov/mmwr – Vaccine Information Statements (VIS) • ACIP website – http://www.cdc.gov/vaccines/acip/ – Vaccine schedules, catch‐up schedule, new recommendations • Immunization Action Coalition (www.immunize.org) National Health Interview Survey 2010 Vaccine Safety/Misinformation – Good consumer information – Resource for “hot topics” Pharmacist’s Role: Safety • Reporting of vaccine adverse events: VAERS – www.vaers.hhs.gov – Documentation of all patient‐reported adverse events • Proper record keeping The dangers of vaccinations to your child's long term health prospects and longevity itself far outweigh any potential benefits touted by the pharmaceutical industry for vaccines. The LIES and misinformation about vaccine benefits from the drug industry is voluminous, overwhelming, and statistically provable. Don't allow your child to go on the chopping block for these Liars and their profit margins. They aren't working for you, they're servants of the corporate elite/Illuminati and the Illuminati has a surreptitious population reduction agenda in place. – Documentation of lot and expiration – Providing proof of vaccination to patient 6 2/10/2014 Pharmacist’s Role: Vaccine Stability Pharmacist’s Role: Vaccine Stability Vaccine 2007; 25, 3980‐3986. Pharmacist’s Role: Vaccine Delivery • Accessibility – See people when they’re “well” – Adolescents • Expertise – Focus on patient‐care – Decreasing distribution functions • Public health emergencies 7 Infectious Disease Update: Trends in Antimicrobial Resistance, Stewardship and Drug Development ACPE # 0008-0000-14-002-L01-P (1 contact hour – knowledge based) Gerard Barber, RPh, MPH, FASHP Coordinator P&T and Clinical Pharmacy Services, Co-Chair, Pharmacy & Therapeutics Committee University of Colorado Hospital Learning Objectives 1. Describe the interplay of pathogen, host, and environment in the development of infectious disease and cite a recent example in which these elements were significant. 2. Citing at least one property of each, distinguish antimicrobial resistance from pathogen virulence. 3. Outline the purpose and multidisciplinary structure of an antimicrobial stewardship program and explain how pharmacists in outpatient and inpatient settings can promote appropriate antimicrobial usage. 4. Describe the potential indications and pharmacologic attributes of new antimicrobials currently in late-stage development. = Disclosures Thepresenterforthiscontinuingpharmacyeducation activityreportsservingonthespeaker’sbureauforCubist Pharmaceuticals. • daptomycin • nonbrandedantimicrobialstewardship http://www.cdc.gov/drugresistance/threatreport2013/pdf/arthreats2013508.pdf WhyisAntimicrobialResistance Increasing? Theenormousamountsofappropriate &inappropriateantibioticusein healthcareinstitutionsisthechief culpritofantimicrobialresistancein developedcountries? EpidemiologicTriad 1. True 2. False Environment NumberofABXRX’es/1000inhabitantsin13 Europeancountries,1994&1997 Molstad,etal.ScandJInfectDis. 2002;34:366371. HicksLA,etal.NEnglJMed2013;368:14611462 WebbBJ,etal.TransplProceed.2013:45:792297 Morbidity and Mortality Weekly Report (MMWR) •MMWR Notes from the Field: New Delhi Metallo--Lactamase–Producing Escherichia coli Associated with Endoscopic Retrograde Cholangiopancreatography — Illinois, 2013 Weekly January3,2014/62(51);10511051 InfectionswithcarbapenemresistantEnterobacteriaceae(CRE)*areincreasingamong patientsinmedicalfacilities(1).CREthatproduceKlebsiellapneumoniaecarbapenemase (KPC)havebeenresponsibleformuchoftheincreaseintheUnitedStates.However,New Delhimetallolactamase(NDM)–producingCREhavethepotentialtoaddtothisburden. Sincefirstreportedin2009,through2012,27patientswithNDMproducingCREhavebeen confirmedbyCDCfromisolatessubmittedbystatelaboratories.SinceJanuary2013,atotal of69patientswithNDMproducingCREhavebeenidentifiedintheUnitedStates;44 patientswerefromnortheasternIllinois. ClinInfectDis.2006:42;647656. RiskFactors • ConcurrentSkin&SoftTissueInfection • IVDA PlacingtheNFL'sLawrenceTynes'MRSAProblemUnder theMicroscope ByDaveSiebert,MD (FeaturedColumnist)onAugust30,2013 LawrenceTynes'PICCcanbeseeninhisrightarmasheholdsaplasticbulbfilled withantibiotics.Courtesy:AmandaTynes'Twitter(@AmandaTynes9). Source: b/r Areliableindicatorofapathogen’s virulenceisitsresistanceto antibiotics? 1. True 2. False AntimicrobialCreep VirulenceResistance Virulence(Properties) • • • • • • Resistance(perpanel) Photobacteriumdamsela Adhesion Colonization Invasion Thermal,other,stabilities Immuneresponsemodification Toxinproduction • • • • • • • • • • • • • • • Ami Amp Amp/sul Cefz Ceftx Ceftz Cip Erta Gent Imi Levo Pip/taz Tet TMPSMX Tobr I S S S S S S S S S S S S S S _______ BarberGR,etal.NEnglJMed2000;342:824 ByrneA,etal.CasesJournal 2009,2:9102 MechanismsofResistancetoAntibiotics Genetic material from external sources (eg, plasmids) Mutational events Enzymatic inactivation (eg, E-lactamase) DNA replication Topo isomerase Protein mRNA Nucleotide biosynthesis RNA transcription Efflux pumps Decreased cell wall permeability Elimination or overproduction of antibiotic target AdaptedfromChopraI.CurrOpinPharmacol2001;1:464469 1.DecreasedPermeability: • Cellwallchanges • Porinchannelchanges • Producebiofilms Protein synthesis Ribosomal protection (eg, tet proteins) mRNA KeepingitSimple: 4MechanismsofResistancetoAntibacterialABX 2.ActiveEfflux: • FQefflux • Tetracyclineefflux 3.EnzymaticInactivation: • lactamases – Carbapenemases • AGME • Methylation 4.TargetSiteChanges: • PBPs • Ribosomalmodification CDCDefinitionofCRE • Resistanttoallofthefollowing3rd generation cephalosporins: Anon.ClinInfectDis.2010:50:10811083 Update – Ceftriaxone – Cefotaxime – Ceftazidime AND… • Nonsusceptibletooneofthefollowing carbapenems: – Doripenem,Meropenem,orImipenem CDCCREToolkit. •MorbidityandMortalityWeeklyReport(MMWR) •MMWR Notes from the Field: Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae Producing New Delhi Metallo-Beta-Lactamase — Denver, Colorado, 2012 Weekly February15,2013/62(06);108108 OnAugust16,2012,theColoradoDepartmentofPublicHealthandEnvironmentwas notifiedoftwopatientsatanacutecarehospitalinDenverwithcarbapenemresistant Enterobacteriaceae(CRE),specificallyKlebsiellapneumoniae (CRKP),isolatedfrom respiratoryspecimensduringJuly–August.Both isolatesproducedNewDelhimetallobeta lactamase(NDM).AreviewofmicrobiologyrecordsidentifiedathirdpatientwithNDM producingCRKPisolatedfromarespiratoryspecimen,admittedinMay.Activesurveillance culturesinSeptemberidentifiedanadditionalfivepatientscolonizedwithNDMproducing CRKP.AninvestigationwaslaunchedbythehospitalandtheColoradoDepartmentofPublic HealthandEnvironmenttoguideinfectioncontrolmeasuresandlimittransmission. CREintheUS • In2001,1.2%reportedatleastonecaseofCRE toCDCviaNHSNorNNIS • In2012,4.6%(181)ofallacutecarehospitals (3918)reportedatleastoneCRE – Rateforshortstayacutecarehospitals(n=145)was 3.9% – Rateforlongtermacutecarehospitals(n=36)was 17.8% – Rateshigherforhospitalswithmedicalschool affiliationsandinhospitalswith>300beds MMWR 2013;62:165170. CREandMortality • 58.8%casefatalityrateforICUpatients • 7080%fatalityrateamongpatientswith bacteremia • Age,mechanicalventilation,malignancy,heart disease,andICUstayhavebeenassociated withincreasedmortalitywithCRE • Removalofthefocusofinfectionwas associatedwithsurvival BilavskyE,etal.CurrOpinInfectDis23:327331. GuptaN,etal.ClinInfectDis.2011;53:6067. InfectionPrevention • Reviewmicrobiologyrecordsforpreceding612 monthstoensurenocaseshavebeenseen – Iffindacase,consideractivesurveillanceorprevalence survey • Handhygiene • ContactPrecautions – Performhandhygienebeforeandafterdonningagown andgloves – Donninggownandglovesbeforeenteringroom – Removegownandglovespriortoexitingthepatient’s roomandperformhandhygiene • AntimicrobialStewardship(AMS) MMWR.2009.58(10):25660. Abouthandwashing… Studiesshowthatthebestratesofappropriatehandwashing techniqueamongseveralcliniciandisciplines(RN,MD,RPh, etc.)areabout: 1. 2. 3. 4. 12% 25% 40% 60% GoalsofAntimicrobialStewardship GetSmartforHealthcare Topics: • Whyinpatientstewardship? • Improvingstewardshipefforts– tools/resources • Evidencetosupportstewardshipefforts • Resourcelibrary (Adapted) GoalsofAntimicrobialStewardship ImprovingClinicalOutcomes IMPROVEMENTMEASURES •DecreaseLOS •ImproveOrganism:ABXmatch •Accuracyempiricregimens •DecreaseOrganism:ABX mismatch •Rapidcorrectionof mismatches •Properdosing(includingPK/PD) •ProperDOT •FacilitateIVtoPO • InpatienttoOPAT •AppropriateABXD/Casindicated n=300interventions AVOIDANCE MANEUVERS •Minimize“CollateralDamage” •BacterialSuperinfection Clostridiumdifficile Stenotrophomonas sp. •Fungalsuperinfection •Waningactivityperantibiogram •HospitalAcquiredInfection,other •IncreaseLOS KuhnS,etal.UCHABXMUE2012/13 32 Stewardshipoptimizespatientsafety:decreased patientlevelresistance Findings Cmax/MIC Criteria Cipro Standard Antibiotic duration 3 days 10 days LOS ICU 9 days Antibiotic 14% resistance/ superinfection ConcdependentABX: AGs,quinolones 15 days 38% T>MIC TimedependentABX: lactams Studyterminatedearlybecauseattending physiciansbegantotreatstandardcare groupwith3daysoftherapy SinghN,etal.AmJRespir Crit CareMed.2000;162:50511. DoseOptimization ExtendedInfusion,PiperacillinTazobactam Amonginstitutionalantimicrobial stewardshipprograms,whichofthe followingpersonnelare,“keyplayers?” 1. 2. 3. 4. 5. LodiseTP,etal.ClinInfectDis.2007;44:35763. Infectiousdiseasephysicians Pharmacists Healthcareadministrators Alloftheabove 1&2only AMSProgram– KeyPlayers • Administration,CSuite“Buyin” • FormalCommitteeStructure • PhysicianChampion(s) – ID,Hospitalists,Hem/Onc – Surgery– rare,butifwillingveryuseful • • • • Pharmacy,specialtytrainingpreferred IP(formerlyIC) – nursing,microbiology QI/QA Other– Informatics,SS/UR AMSProgram– KeyComponents • • • • • • • • Education Prospectiveaudit– intervention&feedback ABXrestriction,authorization ABXordersets,Tx guidelines/pathways/CDSS ABXoptimization Streamlining/deescalation IVtoPO Monitoring– processesoutcomes OwensJr,RC,AmbrosePG,NightingaleCH(Eds).AntibioticOptimization.2005 Dellit TH,etal.Clin InfectDis2007;44:159177. TheCSuite… Type:Administrator,MBA $$$$Oriented • RevenueGeneration – MTMprograms – Retail • Costsavings – ABXClass – OverallABXBudget – UnpaidBeds Type:MD,MPH,RN,RPh MoreClinicallyOriented • Outcomes – 30dayReAdmits – LOS – MedicationSafety – Meet,ExceedCore Measures Mustattach,alignwithtaskgroupsthataimtoimproveorganization initiatives.Goodresults– especiallythoseviewedpubliclyusuallywellreceivedbyallCSuitetypes Asshownbyinvitrotrials,minimizing collateraldamagetofecalmicrobiotaisa clearadvantageinsurotomycin’ssuccessin limitingrelapseofClostridiumdifficile associateddiarrhea? 1. True 2. False OntheHorizon… Surotomycinvs.Vancomycin Surotomycin (PhaseIII) Surotomycin InPhaseIItrialvs vancomycin (n=199subjects): • Proposedindication:Clostridiumdifficile diarrhea • Oral,cycliclipopeptide • 125mgor250mgpo BIDvsvancomycin 125mgpo QID • Eitherdoseregimen:noninferiortovancomycin • Betterglobalcure(4weekspostlastdose) – Lessrecurrenceateitherdose.StatisticallyNS; – Seemswelltolerated. Organism (# isolates tested) Bacteroides fragilis group, including DOT (21) Prevotella spp. (20) Escherichia coli (18) Enterobacter spp (18) Klebsiella spp (20) MIC Range Vancomycin MIC90 MIC Range MIC90 8,192 32 to 256 128 8,192 32 to 512 256 8,192 64 to 256 256 256 to 1,024 1,024 256 to 1,024 1,024 8,192 to > 8192 8,192 to >8,192 4,096 to >8,192 >8,192 > 8,192 DOT=distasonis,ovatus,thetaiotaomicron spp MIC,MIC90inmcg/mL PatinoH,et.al.51st ICAAC2011,Chicago,.IL:posterK205a Adapted,Citron,etal.AAC 2012;56:16131615. Agent Number Chemical Name (Company) AFN-1252 (Affinium) ABT-773 / cethromycin (originally Abbott, Taisho, then Advanced Life Sciences) Study Phase IIa (Acute skin, skinstructure staphylococcal infections) MOA Novel agent (Fabl-inhibitor). Inhibits bacterial fatty acid biosynthesis, targeting the Fabl enzyme in staphylococci [70]. Comments Multicenter trials in US and Canada for targeted oral therapy of acute bacterial skin and skin-structure (ABSSSI) infections due to staphylococci. Inactive against streptococci including enterococci and Enterobacteriaceae. III (moderate – severe Ketolide. Reversibly binds to Potent pneumococcal and community-acquired the 50S subunit of the atypical respiratory organism bacterial pneumona) bacterial ribosome, blocking activity, including macrolideprotein synthesis, preventing resistant strains. Oral bacterial growth and formulation; wide distribution reproduction. Binds at 2 sites into pulmonary compartments of bacterial ribosome including epithelial lining fluid compared with current [71]. Like solithromycin, macrolide agents binding at 1 additional side chain site. (Note: solithromycin, a structures / modifications fluoroketolide discussed in appear to ameliorate CNS detail, binds at 3 sites and has adverse effects of iv and po formulations). telithromycin (lacks telithromycin’s pyridineimidazole side chain) and necessitate additional bacteria mutations to effect resistance. Has FDA orphan-drug-status for prophylaxis in patients exposed to inhalational B. anthracis (anthrax) tularemia Agent Number Chemical Name (Company) BC-3881 (Nabriva Therapeutics) Study Phase II (Acute Bacterial Skin and Skin Structure Infections) MOA Novel pleuromutilin antimicrobial; inhibits bacterial protein synthesis by interaction with 23S rRNA of the 50S bacterial ribosome subunit. Potent in vitro activity against common Gram-positive skin organisms including S. aureus (MSSA and MRSA), coagulasenegative Staphylococcus spp. Streptococcus agalactiae, and S. pyogenes. Also exhibits in vitro activity against a broad spectrum of Gram-positive and gram-negative community respiratory pathogens including S. pneumoniae, including Moraxella catarrhalis and Haemophilis influenza as well as atypical bacteria, Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma pneumonia [74]. Comments Intravenous formulation dosed q12h in first human ABSSSI trial (duration 5 – 14 days). Previously utilized in veterinary medicine or topical use in humans (retapamulin, Altargo®, Altabax® GlaxoSmith Kline) due to toxicity. In ABSSSI demonstrated comparable clinical success to vancomycin. Relatively welltolerated among 141 subjects, most frequent AEs were headache, nausea, and infusion site phlebitis. Expected to move to Phase III trials. Agent Number Chemical Name (Company) Study Phase ACT-179811 / Cadazolid (Actelion) III (C. difficileassociated diarrhea) ACHN-975 (Achaogen) I (safety, doseescalation trial) MOA Novel chimeric quinolonyloxazolidinone; having structural elements of both quinolones and oxazolidinones [77]. Novel, LpxC-inhibitor. LpxC-1 is an inhibitor of LpxC, a deacetylase enzyme present in many Gram-negative bacteria [73]. Comments In vitro studies show bactericidal effect against C. difficile. [Sweden] Phase II dose escalation trials (n=84) comparing cadazolid suspension, 250mg, 500mg, and 1g twice daily versus vancomycin 125mg po 4-times daily. Clinical cure rates, all doses, non-inferior to vancomycin, similar rates of TEAE. Sustained clinical cure, 4 weeks from last dose, favored cadazolid which was as effective at 250mg dose as 1g doses. Subcutaneous injection in murine models infected with MDR-Acinetobacter baumannii do not actively kill or stunt bacterial growth, but stunt endotoxin production and the subsequent ability of the bacteria to activate the sepsis cascade. Development to target MDRO-gram-negatives including MDR-Pseudomonas aeruginosa. Summary Bugsvs.Humans • “Bugs”herelongerthanhumans – Moreofthem,lotsmorethanus • Adapt,generatemuchmorequickly • Noveldrugtomarket:~$1billion • Antimicrobialstewardshipiscritical – Selectivity:lotsof“goodbugs,”neededbugs – Allaspects,trulymultidisciplinary – Institutional,community,agricultural • Timewilltell… BarberGR.AmJHospPharm.2005;62:1143[Editorial] LevySB.TheAntibioticParadox.2002.Perseus2nd ed.Cambridge,MA WhyisAntimicrobialResistance Increasing? • SusceptibleHosts • Lackofbasicinfectioncontrolmeasures • SelectivepressuresABXuse – Appropriate&inappropriate • Unrecognizedcolonization • Unrecognizedreservoirs(environmental) • Movementofpatients,HCWs – HospitalSNF,LTAC – Hospital Community • LackofnovelmechanismABXspast3decades Update on Current Medical Therapy for Diabetes ACPE # 0008-0000-14-003-L01-P (1 contact hour – knowledge based) Michael McDermott, MD Director Endocrinology and Diabetes Practice University of Colorado Hospital Learning Objectives 1. Explain the pathophysiology that underlies current therapies for type 1 and type 2 diabetes mellitus. 2. Given a patient case, describe how to individualize A1C targets and drug choices for that person. 3. Discuss practical aspects of initiating and adjusting old and new therapeutic agents for diabetes mellitus. Disclosure Michael McDermott MD Type 2 Diabetes Mellitus 2014 No Conflict of Interest to Disclose Michael T. McDermott MD Director, Endocrinology and Diabetes Practice University of Colorado Hospital Michael.mcdermott@ucdenver.edu Talk Objectives Diabetes Mellitus Diagnosis 2014 1. Explain the pathophysiology that underlies current therapies for type 1 and type 2 diabetes mellitus. 2. Emphasize the importance of individualization of A1C targets and drug choices. 3. Discuss practical aspects of initiating and adjusting old and new therapeutic agents for diabetes mellitus Diabetes Mellitus Fasting Glucose > 125 mg/dl 2 Hour PP Glucose > 200 mg/dl A1C > 6.5% Pre-Diabetes Fasting Glucose: 100-125 mg/dl 2 Hour PP Glucose: 140-200 mg/dl A1C: 5.7-6.4% Consensus Recommendation: ADA, EASD, IDF 2009 Diabetes Mellitus Diabetes Mellitus 28 Million Americans Projection through 2033 5% Type 2 DM Type 1 DM 2033 Leading US Cause Myocardial Infarction Kidney Failure Amputations Blindness 2014 95% 1 New Case Every 17 Seconds 5,000 New Cases Every Day 2,000,000 New Cases Every Year Huang ES, Diabetes Care 2009; 32:2225-9 1 Pre‐Diabetes Food Consumption 79 Million Americans Density of One US Fast Food Chain Progression to Type 2 Diabetes 11% per Year Prevention of Progression Lifestyle Measures: 60% Metformin: 30% DPP Research Group. N Engl J Med 2002; 346:393-403. DPP Study Tuomilehto J, N Engl J Med 2001; 344:1343-50. Finnish Study Pan XR, Diabetes Care 1997; 20:537-44. Da Qing Study Lack of Exercise Obesity Lack of Exercise The Evolution of Man 2 Diet Exercise Ideal Diet for DM: No Consensus Walk 30 Minutes Daily Mediterranean May Be Best Main Goal Calorie Restriction -130 kcal/day 1 lb = 3500 kcal Deficit: 500 kcal/day Loss of 1 lb/week Loss of 52 lb/year “Well, the Parkers are dead. You had to encourage them to take thirds, didn’t you?” Weight Loss Loss of 1 lb in 27 days Loss of 14 lb in 1 year The 100 Meter Mosey Type 2 Diabetes Mellitus SGLT2 Inhibitors Medication Development Bromocriptine Colesevelam DPP4 Inhibitors Pramlintide GLP-1 Analogs Meglitinides Glucosidase Inhibitor Thiazolidinediones Basal Insulins Rapid Acting Insulins 3500 kcal = 1 lb Insulin 1920 Sulfonylureas 1960 Metformin 1990 2000 Type 2 Diabetes Mellitus Type 2 Diabetes Mellitus Pathophysiology Pathophysiology Based Therapy Glucose Production CNS Effect Insulin Secretion CNS Effect Glucose Production Bromocriptine Metformin Hyperglycemia Thiazolidinedione Insulin Secretion Sulfonylurea Meglitinide Euglycemia SGLT-2 Inhibitor Insulin Resistance Incretin Effect Insulin Resistance 2010 GLP-1 Analog DPP4 Inhibitor Incretin Effect Glycosuria Bile Acid Resin Glucosidase Inhibitor Glucose Absorption 3 Incretin Physiology Glucose Production Appetite Satiety Insulin Glucagon Gastric Emptying Glucose Dependent L-Cells GLP-1 T1/2 = 2 min Due to DPP4 GLP-1 = Glucagon Like Peptide-1 DPP4 = Dipeptidyl Peptidase 4 Incretin Based Therapy Incretin Based Therapy (7-36) T ½ : 1-2 min GLP-1 (9-36) [DPP4] Inactive GLP‐1 Analog / Agonist Resistant to DPP4 Action Prolonged Duration of Analog Action DPP4 Inhibitor Prevents Native GLP-1 Breakdown Prolongs Duration of Native GLP-1 Action Sodium Glucose Transporter 2 Inhibitors Kidneys Filter + Reabsorb Glucose: 180 g/day 90% through SGLT2 GLP-1 Analog: DPP4 Resistant Exenatide (Byetta) Liraglutide (Victoza) Exenatide QW (Bydureon) Dipeptidyl Peptidase 4 GLP-1 Normal SGLT2 Inhibitor Glucose Loss 80-100 g/day 320-400 kcal/day DPP4 Inhibitor: Inhibit GLP-1 Breakdown Sitagliptin (Januvia) Saxagliptin (Onglyza) Linagliptin (Tradjenta) Alogliptin (Nesina) Sodium Glucose Transporter 2 Inhibitors Generic Canagliflozin Dapagliflozin Empagliflozin Luseogliflozin Ertugliflozin Ipragliflozin Tofogliflozin ISIS 388626 EGT 1747 LX 4211 Trade Name Invokana Farxiga NA NA NA NA NA NA NA NA Doses 100, 300 mg 5 mg Glycosuria Glycosuria BG > 180 mg/dl BG > 80 mg/dl Colesevelam Mechanism: Impairs Glucose Absorption Target: Postprandial Glucose Efficacy: A1C ~ 0.5% Name Brand: Welchol (625 mg tabs) Glucose Absorption Dose: 3 Tabs BID or 6 Tabs QAM Additional Benefit: LDL Reduction ~20% Cost per Month: $225 4 Bromocriptine Mechanism: Reduces Insulin Resistance by Enhancing CNS Dopaminergic Tone Target: Postprandial Glucose Efficacy: Monotherapy A1C 0.4-0.6% Enhances Add-on Therapy A1C 0.6-0.9% Dopaminergic Tone Name Brand: Cycloset (0.8 mg tabs) Start: 1 Tab QAM Titrate: Weekly by 1 Tab to total dose of 2-6 Tabs (1.6 – 4.8 mg) QAM Cost per Month: $299 Case History Personalized Diabetes Care Individualize A1C Goal Medications Ismail-Beigi F, Ann Intern Med 2011;154:554-9 Inzucchi S, Diabetes Care 2012; 35:1364-79 Riddle M, Diabetes Care 2012;35:2100-7 Case History HPI: 35 y.o. man with DM2 x 1 years PMH: HTN Lifestyle Modification: Emphasized DM Meds: Metformin 2000 mg PE: Ht 5’11” Wt 236 lb BP 132/82 P 74 Lab: A1C 7.8% SMBG: FBG 95-130 HPI: 78 y.o. woman with DM2 x 20 years PMH: CAD, CHF, A Fib Lifestyle Modification: Emphasized DM Meds: Metformin 1000 mg PE: Ht 5’6” Wt 157 lb BP 139/78 P 94 Lab: A1C 7.9%, Cr 0.7 SMBG: FBG 88-155 What is your target A1C for this patient? A. < 6% B. < 6.5% C. < 7% D. < 7.5% E. < 8% What is your target A1C for this patient? A. < 6% B. < 6.5% C. < 7% D. < 8% E. < 9% Personalized A1C Goal A1C Goal < 7% Recent Onset No / Minimal Hypoglycemia A1C Goal < 7.5% or < 8% Known Cardiovascular Disease Frequent Hypoglycemia Short Life Expectancy Advanced Age Ismail-Beigi F, Ann Intern Med 2011;154:554-9 Inzucchi S, Diabetes Care 2012; 35:1364-79 Riddle M, Diabetes Care 2012;35:2100-7 Case History HPI: 65 y.o. man with DM2 for 18 years. He has CAD with 2 prior MI and moderate CHF. He fears having hypoglycemic episodes, like he has had in the past. DM Meds: Metformin 2000 mg PE: Ht 6’0” Wt 223 lb BP 138/86 P 92 Lab: FBG 108-163 A1C 8.2% eGFR > 60 Lifestyle modification is strongly emphasized. What medication would be least likely to cause hypoglycemia? A. Basal Insulin B. Mealtime Insulin C. Sulfonylurea D. Meglitinide E. GLP-1 Analog 5 Case History HPI: 57 y.o. woman with DM2 for 6 years. She is most concerned about additional weight gain. DM Meds: Metformin 2000 mg PE: Ht 5’6” Wt 232 lb BP 132/82 P 82 Lab: FBG 122-173 A1C 8.0% Personalized Diabetes Care Individualize A1C Goal Lifestyle modification is strongly emphasized. What medication would be least likely to cause weight gain? A. Sulfonylurea B. Thiazolidiendione C. DPP4 Inhibitor D. Basal Insulin E. Mealtime Insulin Type 2 Diabetes: Personalized Medication Choices BG Target FBG > PPBG Metformin Thiazolidinedione Basal Insulin PPBG > FBG Sulfonylurea DPP4 Inhibitor GLP-1 Analog SGLT-2 Inhibitor Meglitinide Glucosidase Inhibitor Bile Acid Resin Bromocriptine Pramlintide Prandial Insulin Effect Low BG Weight Medications Type 2 Diabetes Mellitus: Personalized Management Cost Lifestyle Intervention ++ ++ +++ No No Yes -- + ++ ++ ++ + ++ + + + + + + +++ Yes No No No Yes No No No No Yes -- ------ + +++ +++ +++ ++ ++ +++ +++ +++ ++ + Metformin 3 MOS A1C > Goal Add: GLP-1 Analog DPP4 Inhibitor SGLT-2 Inhibitor Basal Insulin TZD SU Wt Loss No Hypo Wt Neutral No Hypo Wt Loss No Hypo Most Effective No Hypo Low Cost Bile Acid Resin Glucosidase Inhibitor Bromocriptine Pramlintide Basal/Bolus Insulin No Hypo Wt Loss No Hypo Most Effective LDL Reduction No Hypo MTM adapted from Inzucchi S, Diabetes Care 2012; 35:1364-79 Emergency Hospitalizations for Adverse Drug Events Older U.S. Adults, 2007–2009 Hypoglycemia Veterans Hypoglycemia in DM2 2 x Risk CV Events ACCORD Hypoglycemia in DM2 Mortality Rate Zhao Y Seaquist E DM1 and DM2 Hypoglycemia 3.4 x Risk Mortality McCoy R Budnitz DS,N Engl J Med 2011;365:2002-12 Zhao Y, Diabetes Care 2012; 35:1126-32 Seaquist E, Diabetes Care 2012; 35:409-14 McCoy R, Diabetes Care 2012; 35:1897-1901 6 DM2 Medications: Hypoglycemia DM2 Medications: Weight Change Hypoglycemia Rare Hypoglycemia Weight Gain Weight Neutral Weight Loss Insulin Meglitinide Sulfonylurea* Metformin*/** DPP4 Inhibitor** Bromocriptine** Bile Acid Resin** Glucosidase Inhibitor** GLP-1 Analog*** SGLT-2 Inhibitor*** Pramlintide*** Thiazolidinedione Thiazolidinedione Insulin** Meglitinide** Sulfonylurea*/** Metformin* DPP4 Inhibitor Bile Acid Resin Bromocriptine * Inexpensive ** Weight Neutral *** Weight Loss GLP-1 Analog SGLT-2 Inhibitor Pramlintide * Inexpensive ** Hypoglycemia Case History HPI: 48 y.o. man with DM2 x 2 years. CKD from HTN. DM Meds: Metformin 2000 mg, Sitagliptin 50 mg PE: Ht 6’5” Wt 264 lb BP 142/95 P 80 Lab: FBG 86-122 Creatinine 1.7 eGFR 51 A1C 6.6% Lifestyle modification is again emphasized. What would you now recommend? A. Stop Metformin; Start Basal Insulin B. Reduce Metformin dose; Start GLP-1 Agonist C. Reduce Metformin dose; Continue Sitagliptin D. No Change in Therapy E. Low Carbohydrate Diet Metformin Use In People With CKD eGFR > 60 Action Full Dose Metformin Appropriate Monitor Renal Function Annually 45-59 Full Dose Metformin Appropriate Monitor Renal Function Q 3-6 Months 30-44 Half Dose Metformin With Caution Monitor Renal Function Q 3 Months < 30 Stop / Avoid Metformin Lipska KJ. Diabetes Care 2011; 34: 1431-7 Inzucchi S, Diabetes Care 2012; 35: 1364-79 Insulin Ekstrom N, BMJ 2012; ePub ahead Insulin Preparations The Big Gun Insulin Onset Lispro 5-15 min Aspart 10-20 min Glulisine 5-20 min Glargine 1-4 hr Detemir 1-4 hr Regular 30-60 min NPH 1-4 hr Mixes Peak 1-2 hr 1-3 hr 1-3 hr none none 2-4 hr 8-12 hr Duration 3-5 hr 3-5 hr 3-5 hr 22-24 hr 20-24 hr 6-8 hr 12-20 hr 7 Basal Insulin Therapy Insulin Pharmacokinetics Indications Lispro / Aspart / Glulisine Glargine / Detemir Regular NPH 1-2 hr Ketonuria / Ketonemia 8-12 hr +/- 24 hr +/- Peakless 4-5 hr FBG > 250 mg/dl Random BG > 300 mg/dl 2-4 hr Insulin Injection A1C > 11% 6-8 hr 12-16 hr Weight Loss, Polydipsia, Polyuria 24 hr A1C > Goal on 1‐3 Oral Agents Basal Insulin Therapy Basal Insulin Therapy Initiate and Titrate Adjusting Basal to Control AM FBG Glargine / Detemir / NPH HS Start: 10-25 U Daily Check: FBG x 2-3 Days Goal: AM FBG 80-130 Glargine / Detemir / NPH HS Based on AM FBG, Adjust (choose): Mean AM FBG Adjust Adjust Adjust Adjust Adjust > 130 1U 2U 3U 4U 5U No No No No No 80-130 Average Basal Dose (DM2) 0.4-0.5 U/kg or 0.25 U/lb +/- 24 hr Summary Start: 10-25 U Daily Titrate: by 1-5 U every 2-3 days until AM FBG 80-130 Mealtime Insulin Therapy Basal Plus Insulin Indications Initiate and Titrate Lispro / Aspart / Glulisine A1C > Goal – AM FBG at Goal Start: 4-10 U at Largest Meal (Dinner Usually) Titrate: Check BG at Bedtime or Before Next Meal PPBG > Goal – AM FBG at Goal Depending on Meal Covered, Adjust Until: HS BG < 140 mg/dl, OR BG before Next Meal < 130 mg/dl Next (if needed): Add Bolus at 2nd Largest Meal Next (if needed): Add Bolus at 3rd Meal 8 Basal Plus Insulin Basal Plus Insulin Adjusting Bolus Insulin at Dinner Adjusting Bolus Insulin at Lunch Goal: HS BG < 140 B L D Bed Goal: Pre-Dinner BG < 130 B L D Bed Alternative Goal: 2 Hr PPBG < 180 mg/dl Alternative Goal: 2 Hr PPBG < 180 mg/dl Basal Bolus Insulin Basal Bolus Insulin Initiate and Titrate Adjusting Bolus with Each Meal Lispro / Aspart / Glulisine Goal: Next Pre-Meal BG < 130 Start: 4-5 U at Each Meal Titrate: Check Pre-Meal BG and HS BG Daily Goal: HS BG < 140 Adjust Until: BG before Each Meal < 130 mg/dl, AND HS BG < 140 mg/dl Consider: Carbohydrate Counting / Flexible Dosing Using C:I Ratio and Correction Factor (CF) B L D Bed Alternative Goal: 2 Hr PPBG < 180 mg/dl Goal: AM FBG 80-130 Average Total Daily Dose (DM2) 0.8-1.0 U/kg or 0.4 U/lb Obesity Treatment as DM2 Strategy Phentermine / Topiramate (Qsymia) Medications – FDA Approved Weight Effects Phentermine: appetite Phentermine / Topiramate (Qsymia): appetite Lorcaserin (Belviq): appetite Orlistat (Xenical, Alli): fat absorption GLP‐1 Analogs: appetite [DM2] SGLT2 Inhibitors: urine glucose [DM2] Wt Loss 10-12% Indications: BMI > 30 kg/m2 BMI > 25 kg/m2 with obesity related disease Gadde K, Lancet 2011; 16;377(9774):1341‐52 9 Phentermine / Topiramate (Qsymia) Phentermine / Topiramate (Qsymia) Glucose Effects Clinical Notes 743 Patients (BMI 27-45): Prediabetes (292), Metabolic Syndrome (451) RCT: Q 7.5/46 mg, Q15/92 mg, or Placebo (Lifestyle) x 108 weeks Qsymia Qsymia Lifestyle 7.5/46 mg 15/92 mg + Placebo Combination: greater efficacy, fewer side effects Weight Loss: 10‐12% (20‐24 lb for 200 lb person) Doses (Phentermine / Topiramate): 3.75/23 mg, 7.5/46 mg, 15/92 mg Weight Loss 10.9% 12.1% DM2 Prevention 70.5% 78.7% 2.5% Cost: $150.00/month Off‐Label: use of generic Phentermine + Topiramate Garvey WT, Diabetes Care 2013;doi:10.2337/dc13-1518 (e-pub) Lorcaserin (Belviq) Weight Effects Lorcaserin (Belviq) Glucose Effects 604 DM2 Patients (BMI 27-45): RCT: Lorcaserin 10 mg QD vs 10 mg BID vs Placebo x 1 Year Wt Loss 4-5% Smith SR, N Engl J Med 2010;363:245‐56 Lorcaserin (Belviq) Clinical Notes Serotonin 2C Receptor Agonist Satiety Weight Loss: 4‐5% (8‐10 lb for 200 lb person) Previous Serotonin Agonists: Dexfenfluramine + Fenfluramine caused cardiac valve disease 2C Receptor: in Brain only and not in Heart Lorcaserin: No Evidence of Heart Valve Disease Cost: $?/month Off‐Label: Use with Phentermine (unclear safety) O'Neil PM, Obesity 2012; 20:1426-36 Treatment of Obesity Bariatric Surgery Multiple Surgery Types Available Indications: BMI > 40 kg/m2 BMI > 35 kg/m2 with obesity related disease 10 Bariatric Surgery Bariatric Surgery Weight Loss – 15 Years Mortality – 15 Years Hazard Ratio (Adjusted) 0.71 (p=.01) 29% Control Banding 14% Vertical Banded Gastroplasty 16% Gastric Bypass 25% Study of Obese Subjects (SOS) Sjostrom L. N Engl J Med 2007;357:741-52 Study of Obese Subjects (SOS) Sjostrom L. N Engl J Med 2007;357:741-52 Bariatric Surgery Bariatric Surgery Mortality Rate: < 1% Adverse Events: ~ 20% Beneficial Effects: Randomized Trial: 43 Obese Patients with DM2 Roux-en-Y Surgery vs Intensive Lifestyle and Medications One Year Follow-up Roux-en-Y Surgery Lifestyle + Medications Weight Loss 25.8% 6.4% DM2 Remission 60% 6% Buchwald, JAMA 2004; 292:1724 Maggard, Ann Intern Med 2005; 142:547 DeMaria E, NEJM 2007; 356:2176 Sjostrom L, NEJM 2007; 357:741 Cummings D, Obesity Week 2013, Nov; Abstract T-66 EndoBarrier Cardiovascular Disease Diabetes Mellitus Hyperlipidemia Hypertension Sleep Apnea Mortality Summary of Type 2 Diabetes Management Obesity is the most important risk factor for DM2 Lifestyle modification can prevent DM2 and must be part of all DM2 management plans DM2 results from excess hepatic glucose production, insulin resistance and relative insulin deficiency Medications are available to address the multiple known pathophysiological factors in DM2 A1C < 7% prevents microvascular complications Hypoglycemia should be avoided Glycemic goals and therapy should be personalized Obesity treatment beneficial for DM2 managment 11 Thank You Appendix Type 2 Diabetes Mellitus Prevention and Treatment Diet Lifestyle Modification No consensus regarding ideal diet for DM Main Goal: Calorie Restriction 1 lb = 3500 kcal 500 kcal/d deficit = 1 lb/week = 52 lb/year Exercise Walk 30 min/day ~ 130 kcal 130 kcal/d deficit = 1 lb/27 days = 14 lb/yr Weight Loss Metformin Mechanism: Reduce insulin resistance (liver > muscle) Reduce hepatic glucose production Products available Metformin Glucophage XR Glumetza Start: 500 mg qd short acting preparation; weekly to 2000-2500 mg qd (BID dosing) Start: 1000 mg qd long acting preparation; to 2000 mg qd in 1-2 weeks (QD dosing) Avoid: eGFR < 30 ml/min; Severe liver disease Sulfonylureas Thiazolidinediones Mechanism: Reduce insulin resistance (fat, muscle, liver) Products available Pioglitazone (Actos) Rosiglitazone (Avandia) Start: low or middle dose; every 4-6 weeks, as needed, to highest dose Avoid: Class 2-4 CHF; significant edema; Liver disease (except NASH) Caution: Chronic renal failure (edema) Bladder cancer Mechanism: stimulate insulin secretion Products available Glyburide Glipizide, Glipizide XL/ER Glimepiride (Amaryl) Start: low, to maximum dose, as needed Avoid: Chronic renal failure (Glipizide OK) 12 Meglitinides Mechanism: stimulate insulin secretion Products available Repaglinide (Prandin) Nateglinide (Starlix) Start: lowest dose before each meal; to highest dose TID, as needed Avoid: Chronic renal failure (Repaglinide OK) Amylin Based Therapy Mechanism: Glucagon Suppression Postprandial Glucose Reduction Products available Incretin Based Therapy Mechanism: Glucose-dependent Insulin Stimulation Glucose-dependent Glucagon Suppression GLP-1 Analog / Agonist Exenatide (Byetta): Start 5 mcg BID; to 10 mcg BID in 1 month Liraglutide (Victoza): Start 0.6 mg QD, to 1.2 mg QD in 2 wks, to 1.8 mg QD in 2 wks Exenatide QW (Bydureon): 2 mg QW DPP4 Inhibitor Sitagliptin (Januvia): 100 mg QD ( dose in renal failure) Saxagliptin (Onglyza): 2.5 or 5 mg QD ( dose in renal failure) Linagliptin (Tradjenta): 5 mg QD (no dose change in renal failure) Alogliptin (Nesina): 25 mg ( dose in renal failure) Flexible Mealtime Bolus Insulin Bolus Components C:I Ratio: Gm of Carb covered by 1U Insulin CF: Expected BG drop from 1U Insulin Add if pre-meal BG high Pramlintide (Symlin) Type 1 DM: Starting Calculations at UCH Start 15 ug TID. q 3 days to 30 ug TID, C:I = 500/TDD (~15:1) CF = 1650/TDD (~50:1) to 45 ug TID, and to 60 ug TID. Type 2 DM: Start 60 ug TID. in 3-7 days to 120 ug TID. Goal for Dose Adjustment 2 Hr PPBG < 180 mg/dl or Next Pre-meal BG < 130 mg/dl or PPBG 30-50 mg/dl above Pre-meal BG 13 Improving Outcomes from Pre-diabetes to Diabetes: Strategies to Minimize Progression and Complications ACPE # 0008-0000-14-004-L01-P (1 contact hour – knowledge based) Samuel Ellis, PharmD, BCPS, CDE Associate Professor Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Denver Learning Objectives 1. Outline the current evidence for the effectiveness of lifestyle interventions for the prevention or delay of progression to diabetes in patients who are at risk for diabetes. 2. Describe the non-pharmacotherapeutic options to improve glucose control and reduce complications in patients with diabetes. 3. Given a profile of a patient with diabetes, provide two to three methods that a pharmacist could use to support the patient’s efforts to improve glucose control and subsequent diabetes complications. DisclosureStatement Improving Outcomes from Pre-diabetes to Diabetes: – Ihavenorelevantfinancialrelationshipswithcommercialinterests pertainingtothecontentpresentedinthisprogram. Strategies to Minimize Progression and Complications February22,2014 Sam Ellis, PharmD, BCPS, CDE Associate Professor University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Objectives 1. Outlinethecurrentevidencefortheeffectivenessoflifestyle interventionsforthepreventionordelayofprogressiontodiabetesin patientswhoareatriskfordiabetes. 2. Describethenonpharmacotherapeuticoptionstoimproveglucose controlandreducecomplicationsinpatientswithdiabetes. 3. Givenaprofileofapatientwithdiabetes,provide23methodsthata pharmacistcouldusetosupportthepatient’seffortstoimprove glucosecontrolandsubsequentdiabetescomplications. Questions: Take23minutesandthinktobrainstorm Q1:Whatdoyoudoforyourpatientswithdiabetes? Q2:Whatshouldwebedoingforourpatientswith diabetes? Age-Adjusted Prevalence of Obesity and Diagnosed Diabetes Among U.S. Adults Aged 18 Years or older DiabetesPrevention Obesity (BMI 30 kg/m2) 1994 • RoleofDiet • RoleofExercise • RoleofMedications No Data Diabetes 2010 2000 <14.0% 1994 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0% 2010 2000 No Data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% >9.0% CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics DefiningPreDM:Categoriesof IncreasedRisk A1c Values Impaired fasting glucose Impaired glucose tolerance PrevalenceofPrediabetesintheUS In20052008: • 35%ofU.S.adultsaged20yearsorolderhad prediabetes • 50%ofthoseaged65yearsorolderhadprediabetes • ApplyingthispercentagetotheentireU.S. populationin2010yieldsanestimated79million Americansaged20yearsorolderwithprediabetes. ADAcriteriafortestingfordiabetesin asymptomaticpatients 1. Alladultswhoareoverweight(BMI25)andhave 1ormoreadditionalriskfactors – Physicalinactivity – Firstdegreerelativewithdiabetes – Highriskrace/ethnicity(e.g.,AfricanAmerican,Latino,Native American,AsianAmerican,PacificIslander) – Womenwhodeliveredbaby>9lbsorwithGDM – HTN – HDL<35mg/dLand/orTG>250mg/dL – WomenwithPCOS – A1C5.7%,IGT,orIFGonprevioustest – Otherconditionsassociatedwithinsulinresistance – HistoryofCVD StudytoPreventDiabetes:Diabetes PreventionProgram(DPP) x Topreventordelaythedevelopmentof type2diabetesinpersonswithimpaired glucosetolerance(IGT) Knowler WC, et al. for the Diabetes Prevention Program Research N Engl J Med. 2002;346:393-403. ADA 2013 Standards of Care. Table 4, pS14. StudyInterventions LifestyleIntervention Eligible participants Anintensiveprogramwiththefollowing specificgoals: Randomized Standard lifestyle recommendations • > 7% loss of body weight and maintenance of weight loss – Dietary fat goal -- <25% of calories from fat Intensive Lifestyle (n = 1079) Metformin Placebo (n = 1073) (n = 1082) – Calorie intake goal -- 1200-1800 kcal/day • > 150 minutes per week of physical activity DiabetesIncidenceRatesbyAge DPP: Incidence of Diabetes – Placebo:11%/yearincidence – Metformin:7.8%/yearincidence* – Lifestyleintervention:4.8%/yearincidence* • Riskreduction: – 31%bymetformin Cases/100 person-yr • Metformin,intensivelifestylemodificationdelayedor preventedtype2diabetesvsplacebo(11%/year incidence) Lifestyle Metformin Placebo 12 8 4 – 58%bylifestyle – 39%lifestylevsmetformin 0 25-44 (n=1000) *P<0.001 vs placebo Knowler WC, et al. for the Diabetes Prevention Program Research N Engl J Med. 2002;346:393-403. HowDoWeReplicateDPP CDC:NationalDiabetesPreventionProgram www.cdc.gov/diabetes/prevention/about www.cdc.gov/diabetes/prevention/pdf/dprp_standar ds_09022011.pdf Nationallyrecognizeddiabetespreventionprogram InauguralpartnersweretheYMCAandUnitedHealth Evidencedbasedprogramusinglifestylecoaches 4pharmaciesnationallyrecognized 45-59 (n=1586) > 60 (n=648) Age (years) The DPP Research Group, NEJM 346:393-403, 2002 OutcomesAssociatedwiththe YMCADPPModel Intervention: - Standard curriculum - 12 sessions - 60-90 minutes each - Over 8 months Colorado: Firstcertifiedprogramin2013 CurrentlynopharmaciesarerecognizedinCO Ackermann RT, etal. Chronic Illness. 2011: 7(4) 279–290 WhatistheRoleofthePharmacist? • Whatroledopharmacistshaveindietary educationanddiseaseprevention? ReimbursementforNationalDPP Thirdpartyreimbursementforrecognizedsites Reimbursementisbasedonperformanceofthe DPP Weightloss Percentofvisitsattended Reimbursementisbetterforpreventionthan management OtherStrategiestoImproveGlucose Control CostsofDiabetesMedication Nonadherence ¾ 4050%ofpatientswithDiabetesareconsidered nonadherent(basedonMPR<80%) Brainstormfor12minutesaboutwhatother interventions(excludingdietandexercise)may improveglucosecontrolinapatientwith diabetes • 37%lesspharmacycosts • 7%loweroutpatientcosts • 41%higherinpatientcosts Improvingmedicationadherencewouldresultin costsavingsof$661millionto$1.16billionperyear Egede LE, etal. Diabetes Care 35:2533–2539, 2012 ClinicalImplicationsofNonadherence MedicationAdherence Howdoyoucurrentlyassessmedicationnonadherence • KPCOData inover 11,000pts • UsedPDC <80% Howdoyouknowyourpatientisadherent? Refills Selfreport(Morisky) Proportionofdays covered(PDC) ContinuousData Ho MP, etal., Arch Intern Me. 2006;166:1836-41 BenefitsofIncrementalChangesto Adherence • InitialDrugTx • Each10% increasein adherence resultedin0.1% increase • Otherstudies havereported upto0.25% decreaseinA1c foreach10% improvementin adherence Rozenfeld Y, etal. Am J of Managed Care. 2008;14:71-75 BarrierstoMedicationAdherence • Lackofknowledge – Unsureofmedicationbenefits – Concernofmedicationsafety • Fearofhypoglycemia – Insulin – SU • Costs • Myths(many) StrategiestoImproveMedication Adherence • • • • • • • • HowtoMotivatethePatient 1. Motivationalinterviewing isaperson centered,directivemethodof communicationforenhancingintrinsic motivationtochangebyexploringand resolvingambivalence PatientEducation AutomatedRefillSystem Refills MedicationDiscountPrograms SpecialPackaging Reminders Technology MotivationalInterviewing • R =Resistingthe rightingreflex; • U=Understandingandexploringthepatient’sown motivations; • L =Listeningwithempathy; • E =Empoweringpatients,encouragingtheirhopeand optimism. GlucoseTestingtoImproveGlucose Control CostsofSMBGinUSA • Whoshouldtesttheirbloodglucose? • HowoftenshouldapatientwithdiabetestesttheirBG? • Whoisresponsibleforprovidingmeaningtotheseself monitoringofbloodglucose(SMBG)values? • WhatistheroleofthedoctorinevaluatingSMBGvalues? • Doesitimproveglucosecontrol? Sam’sSimpleMath • • • • • 26millionpeoplewithDM(T1andT2DM) 7millionundiagnosed Assumethat10millionAmericanstestoncedaily $0.50 $1.00perstrip $510million/dayOR$150300million/month $1.83.6Billionperyear BenefitsofGlucoseTesting DiabetesType H1c Effects Hypoglycemia Type1diabetes Possiblebeneficialeffectin loweringHbA1c Possiblebeneficialeffectin identifyinghypoglycemic events (lowlevelevidence) (lowlevelevidence) Type2usinginsulin Possiblebeneficialeffectin Possiblebeneficialeffectin loweringHbA1c identifying (lowlevelevidence) hypoglycemicevents(low levelevidence) Type2notusinginsulin Noclinicallyrelevanteffect Nobeneficialeffectin inloweringHbA1c identifyinghypoglycemic (highlevelevidence) events (moderatelevelevidence) Cefalu WT, Diabetes Care. 2013;36:176 ADAGuidelineStatementon SMBG 1.Whenprescribedaspartofabroadereducational context,SMBGresultsmaybehelpfultoguide treatmentdecisionsand/orpatientselfmanagement forpatientsusinglessfrequentinsulininjectionsor noninsulintherapies.(E) 2.WhenprescribingSMBG,ensurethatpatientsreceive ongoinginstructionandregularevaluationofSMBG techniqueandSMBGresults,aswellastheirabilityto useSMBGdatatoadjusttherapy.(E) ADA Standards of Care, 2013 Sam’sIdealisticSMBGGoal FrequencyofTesting 1. Allpatientswouldtestwithapurpose 2. Testinpairsorstructuredglucosetesting 3. Allpatientswouldbeeducatedonhowto problemsolveandmanageabnormalBGs oridentifytrends 4. Allproviderswoulddownloadmeters 5. Allproviderswouldinterpretreports 6. Drugtherapywouldtargetglucosedefects HowoftenshouldwetellpatientstotestBG? (weekly,daily,twicedaily,4timesdaily7 timesdaily) • StructuredTestingisrelativelynew • Takesadvantageofseveraldaysofmore intensemonitoring • Patientstestwithapurpose STePStudy:360ViewSMBGlog Study:STePProgram • PatientsenrolledtostructuredSMBGtesting program(enhancedgroup)orusualcare • Patientsaskedtokeeprecordsinaglucoselog • Duration:12months • Enhancedgrouppatientsandprovidersreceived trainingoninterpretationofdata Polonsky W, etal. Diabetes Care, 2011 STePStudy:360ViewSMBGlog SMBG:StructuredvsUsualCare Polonsky, W. Diabetes Care 2011 SMBG:StructuredvsUsualCare adherentvsnonadherent RoleofthePharmacist ClinicalInertia:STePStudy Conclusions • 57%weightlossthroughdietandexercisereducesthe progressiontodiabetesby58%inpatientswithpredm • Whatistheroleofthepharmacists? Summary: 1. SMBGisbeneficialinpatientswithtype2diabetes (notoninsulin)ifusedappropriatelybythe patientandprovider 2. Patientsandprovidersneedtoevaluatedata (downloads) 3. Improvededucationaleffortsforprovidersand patients • Thisweightlosscannowbereimbursedthrougha nationallyrecognizedDPP • Medicationnonadherenceoccursin4050%ofpatients withdiabetesandpharmacistshaveanexcellent opportunitytoaddressthisissue • TestingBloodglucosesinastructuredmannercangive theproviderandpatientabetterunderstandingoftheir diabetescontrolwhichleadstoimprovedprescribingand overallglucosecontrol. Summary Pharmacistscanplayasignificantrolein improvingdiabetesselfcarethroughimproving: • Diet/exercise(forprediabetesanddiabetes) • Improvingmedicationadherence • Educatingpatientsandprovidersabout structuredglucosetesting 2014 Regulatory and Legislative Update: State and National Perspectives ACPE # 0008-0000-14-005-L03-P (1 contact hour – knowledge based) Val Kalnins, RPh Executive Director Colorado Pharmacists Society Learning Objectives 1. Discuss the latest developments concerning the Affordable Care Act and how they will affect the practice of Pharmacy. 2. Summarize the latest developments in state and national initiatives and legislation related to pharmacy. 3. Describe the impact of FDA, DEA, and state board of pharmacy rules and proposed rules of 2012-2013. 2/10/2014 Objectives 2014 Regulatory and Legislative Update: State and National Perspectives Val Kalnins, R.Ph CPS Executive Director • Discuss the latest developments concerning the Affordable Care Act and how they will affect the practice of pharmacy. • Summarize the latest developments in state and national initiatives and legislation related to pharmacy. • Describe the impact of FDA, DEA and state board of pharmacy rules and proposed rules of 2012‐2013. February 22, 2014 H.R. 3200 America’s Affordable Health Choices Act Disclosure Statement – no financial relationships to disclose Val Kalnins has no relevant financial relationships with commercial interests pertaining to the content presented in this program. Pharmacy Principles of HCR Introduced 7/14/2009 by Rep. Dingell Sets provisions governing health insurance plans and issuers • Five different bills • • – – 3 in the House of Representatives (Tri‐Committee 2 in the Senate (HELP and Finance) Pharmacy Principles of HCR Principle I: Quality and Safety • • • Improve Quality and Safety of Medication Use Assure Patient Access to Needed Medications & Pharmacy Services Promote Pharmacy and Health Information Technology Interoperability Provide access to MTM services Provide compensation for MTM services Principle II: Infrastructure Include pharmacists in workforce strategies Provide patient choice of MTM provider (w/in their plan) Provide appropriate reimbursement for dispensing‐ related services Ensure no artificial barriers to generic substitution 1 2/10/2014 Pharmacy Principles of HCR Principle III: Health Information Technology Provide pharmacists access to patient information in an electronic, interoperable, multi‐directional format Establish and provide pharmacist access to grants Ensure access to information, while protecting patient information Pharmacy Principles of HCR • • • • • Health Care Reform – Final Bill HR 3590 Amend the Internal Revenue Code of 1986 to modify the first‐time homebuyers credit in the case of members of the Armed Forces and certain other Federal employees PL 111‐148 The Patient Protection and Affordable Care Act Repeal of ACA Unconstitutional ‐ Commerce Clause ‐ Taxing Power of Congress • Lower Courts Decisions • 5/4 ruling upholds almost all the ACA • Provide Medication Therapy Management Services Include Pharmacists as Part of Integrated Care Models Include Pharmacists in Payments for Transitional Care Activities Conduct a MTM Pilot Include Pharmacists in Workforce Strategies Health Care Reform – Final Bill H.R. 4872 Health Care and Education Reconciliation Act of 2010 (Final Health Care Legislation) PL 111‐152 Reconciliation Act Supreme Court Ruling • Neither “side” liked the opinion – “Against” disagreed about the individual mandate – “For” disagreed that the individual mandate was a tax and therefore constitutional • What was lost: states don’t have to accept the Medicaid expansion or lose all Medicaid funding 2 2/10/2014 Repeal of ACA The House of Representatives has voted ____ times to repeal or “dismantle” ACA These repeal votes A. are for political “show” B. affect public perception of ACA C. have had major effects on ACA D. all of the above Web Site October 100,000 enrolled November 250,000 enrolled December 975,000 Sec. Sebelius Announces 2.1 Million enrolled (12/30/13) • 3.5 % have actually paid a premium and thereby enrolled in coverage. • System that transmits information to insurers? • • • • Enrollment Demographics • Hard to Say • Are young adults enrolling? 22% (data from 7 state exchanges) 40% hoped or expected • “Death spiral?” • Are insurance companies worried? Enrollment • As of December 31, 3013, ____ million people now have health coverage because of the Affordable Care Act • • • • A. 3.7 B. 6.4 C. 8.1 D. 9.6 Insurance Co Protections Three R’s • Reinsurance Pot of money for reimbursement • Risk Corridors If insurers costs higher than planned, gov’t pays excess • Risk Adjustment Insurance Co’s pay each other 3 2/10/2014 Like Your Plan – Keep It • Grandfathered Plans – those that existed on March 23, 2010 are exempt from some new requirements. • These plans can continue to "innovate and contain costs by allowing insurers and employers to make routine changes without losing grandfather status." Like Your Plan – Keep It • HHS Rules‐Lose Grandfather Status if: ‐ Cut or Reduce Benefits ‐ Raise Co‐Insurance Charges ‐ Significantly Raise Co‐Payment ‐ Significantly Raise Deductibles ‐ ‐ Significantly Lower Employer ‐ ‐ Add or tighten annual limit ‐ Change Insurance Companies. Contributions Like Your Plan – Keep It Like Your Plan – Keep It • How many have had their insurance cancelled? 4.7 Million • Only affect those who buy their own insurance? 5% of population=15 Million • Those with Employer Sponsored Insurance=156 Million • Federal Register, page 34552 6/17/10 “the Departments’ mid‐range estimate is that 66 percent of small employer plans and 45 percent of large employer plans will relinquish their grandfather status by the end of 2013.” What The ACA Does ACA Shortcomings Helps 32 Million Get Insurance Prohibits use of preexisting conditions as a reason for denial of services Covers preventive services under Medicare. Closes Medicare Part D “donut hole.” Covers children until age 26 Mandates coverage by 2014 Creates “Exchanges.” • No requirements to change care delivery and payment systems to decrease costs/increase value (supports pilot programs only) • Penalties on business too low (penalties lower than providing health insurance) • Penalties on individuals too low • Capacity improvements will lag demand • Not all will be covered (34 million nation‐wide.) • • • • • • • 4 2/10/2014 ACA: 2014 ACA: 2014 • • Mandate insurance coverage • Penalty of $95 or 1% of income Penalty of $695 or 2.5% of income (2016) Penalty applies to each adult in household $2085 annual limit for families Not fined if financial hardship, American Indian, religious exemption or prisoner. – Not fined if cheapest plan>8% of income – Not fined if income too low – – – – – • • • • Establish Insurance Exchanges Insurance companies can’t place lifetime or annual limits. Denial of coverage for preexisting conditions prohibited. Denial of coverage for health conditions, past medical problems or gender prohibited. Insurers can charge those >65 no more than 3 x the amount charged to younger adults. Expands Medicaid ACA: Pharmacy Provisions ACA: Pharmacy Provisions • Where “Pharmacist” appears in the 2409 page document ‐ Innovations in Health Care Workforce (3021) ‐ Independence at Home Pilot(3024) ‐ Reducing wasteful dispensing of outpatient Rx drugs in LTCFs (3310) ‐ Grants or Contracts to implement Med Management Services in treatment of chronic diseases (3503) ‐ Health Care Workforce (5101 pg 1272) ‐ Geriatric Career Incentive Award (5305 ‐ Improvement in MTM Part D (10328) • Team members for “independence at home medical practice” and “patient‐centered medical homes” ‐ 5 – Access to pharmacist‐delivered medication management services including medication reconciliation • Providers for pharmacist‐delivered medication management services under scope of practice (specifically for high risk patients) • Medicare Part D plan sponsors must offer medication management services with annual pharmacist review ACA: Pharmacy Provisions • Collaborative pharmacy practice agreements as allowed by state law and scope of practice; can include: – patient assessment – formulating treatment plan – selecting, initiating, modifying, recommending changes to or administering medication therapy – patient monitoring ACA: Pharmacy Provisions • Medication Therapy Management must be offered by Med D Plans to include: ‐ review of individual’s medications ‐ written or printed summary ‐ follow up interventions ‐ automatic enrollment of beneficiaries ‐ offer opt‐out option ‐ assessment, at least quarterly, of those not enrolled in MTM program 5 2/10/2014 ACA: Pharmacy Opportunities ACA: Pharmacy Opportunities • • • • • Establishes Center for Medicare and Medicaid Innovation (3021) Pilot Program for Integrated Care (2704) Independence at Home Demonstration (3024) Community‐Based Care Transitions Program (3026) Community Health Team to Support the Patient Centered Medical Home (3502) ACA: Pharmacy Opportunities • • Medication Management Grant Program Establishes National Health Care Workforce Commission ‐ definition of “health care workforce” includes pharmacists ‐ definition of “health professionals” includes clinical pharmacists, representatives of schools of pharmacy and pharmacists “Improving Care Transitions Optimizing Medication Reconciliation” • Scope of practice could enhance role in patient care • Transition of Care • Medication Reconciliation • Medical homes, Accountable Care Organizations and other delivery/payment system reform pilots could support an expanded role in chronic disease management and medication counseling, monitoring, etc. • ASHP and APhA released a white paper highlighting the need for pharmacists to take leadership in implementing medication reconciliation. • Applying a standardized approach will help cut down on medication errors ‐ when approximately half of them are attributed to communication at transitions of care. • White paper indicated a strong medication reconciliation strategy uses HIT solutions to help share important clinical information. Med Rec and Meaningful Use Reducing Hospital Readmissions • Incorporating pharmacists in all stages of the medication reconciliation process remains vital for providing safe and effective patient care • CMS recently released stage 2 criteria for meaningful use of certified electronic health records (EHR) technology • Newly released criteria/objectives/measures: – medication reconciliation: 'Perform medication reconciliation for more than 65 percent of transitions of care in which the patient is transitioned into care..' • The Hospital Readmissions Reduction Program levels penalties against hospitals with "excessive readmissions" after risk adjustments are applied. • penalties will apply to all Medicare payments, not just those associated with excessive readmissions. • reimbursement reductions begin in 2013, with penalties determined by clinical outcomes monitored in federal fiscal 2012 (Oct 2011‐Oct 2012) • Utilize Treatment Guidelines 6 2/10/2014 National Legislation and Initiatives Opportunities for Pharmacy • Pharmacists Recognized as Health Care Providers • Report to U.S. Surgeon General • Patient Centered Primary Care Collaborative (PCPCC) • Comprehensive Medication Management • Accountable Care Organizations FDA/DEA & State Board of Pharmacy Rules • • • • Return and Disposal of CS (DEA Rule) Drug Shortages (FDA Rule) Behind the Counter Drugs (FDA Rule) CO Board of Pharmacy Rules • • • • • Compounding (Federal) Provider Status (CA) Improve Access to MTM Services Better Care Programs Reschedule Hydrocodone Combination Products State Legislation and Initiatives • Colorado Coalition for Prescription Drug Abuse Prevention • Prescription Drug Monitoring Program • Medication Synchronization • Telepharmacy • Compounding 7 Drug Interactions Every Pharmacist Should Know ACPE # 0008-0000-14-006-L01-P (1 contact hour – knowledge based) Daniel Malone, RPh, PhD Professor College of Pharmacy University of Arizona Learning Objectives 1. Describe the basic mechanisms for drug-drug interactions. 2. Identify medications involved in clinically relevant interactions. 3. Given selected drug-drug interactions, determine possible management strategies to minimize or avoid harm. 2/24/2014 DRUG-DRUG INTERACTIONS EVERY PHARMACIST SHOULD KNOW Dan Malone, RPh, PhD Professor University of Arizona Terminology • Drug-drug interaction (DDI): Clinically meaningful alteration in the effect of one drug (object) as a result of coadministration of another (precipitant) • Potential drug-drug interaction (PDDI): Co-prescription or co-administration of drugs known to interact, regardless of whether harm ensues DDI Prevalence in Elderly • Elderly veterans with new DDI at ED discharge:1 13% • Older adults exposed to a “major” DDI:2 4% • Medicare Part D enrollees exposed to certain DDIs: 7.3% 1) J Am Geriatr Soc. 2008;56:875-80. 2) JAMA. 2008;300:2867-78. DISCLOSURE STATEMENT Daniel Malone I have no relevant financial relationships with commercial interests pertaining to the content presented in this program. Drug Interaction Knowledge and Information Sources • Prescriber knowledge is lacking1,2 • 42.7% of drug pairs correctly identified1 • Information sources use by prescribers3 also lacking knowledge4 • Pharmacists 68.4% • PDA 15.8% similar to online resources • Alerts 10.8% • Other sources 5.1% known to be problematic e.g., compendia, labeling 1) Ko et al. Drug Saf. 2008;31(6):525-536. 2) Glassman. Med Care. 2002;40(12):1161-1171. 3) Ko et al. Res Social Adm Pharm. 2008;4(4):355366. 4) Weideman et al. Am J Health Syst Pharm 1999 56: 1524-1529. Health Systems Approach to DDIs • Evidence for DDIs is lacking • Very few well-controlled studies • Lack of concordance among DDI compendia1 • Differing severity rating systems, terminology, methodologies • Limitations of DDI clinical decision support2-4 • “Alert fatigue” • High rates of alert override 1) Abarca et al. J Am Pharm Assoc (2003). 2004;44(2):136-141. 2) Grizzle et al. Am J Manag Care. 2007;13(10):573-578. 3) Murphy et al. Am J Health Syst Pharm. 2004;61(14):1484-1487. 4) Abarca et al. J Manag Care Pharm. 2006;12(5):383-389. 1 2/24/2014 Improving Knowledge to Prevent Exposure to Potential DDIs Drug A + Drug B • Understanding basic concepts allows for more Drug Interaction Defenses Prescriber’s Knowledge Computer Screening rationale DDI predictions • Prevent adverse DDIs by making patient- and situation-specific assessments • When appropriate: Pharmacist’s Knowledge Patient Risk Factors Pharmacogenetics Drug Administration Patient Education • Avoid concomitant administration • Implement alternative therapeutic strategies Defenses Monitoring • Take precautionary measures ADR Hansten PD, Horn JR. Modified from: James Reason, Human Error, 1990 A+B Pharmacokinetic Drug Interactions “When the Holes Line Up” Prescriber’s Knowledge Computer Screening Pharmacist’s Knowledge Patient Risk Factors Drug Administration Patient Education Monitoring Defenses ADR Latent Failures Hansten PD, Horn JR. Modified from: James Reason, Human Error, 1990 Drug Interaction Mechanisms • Pharmacodynamic • Additive or antagonistic pharmacologic effects • Pharmacokinetic Absorption • Distribution • Metabolism • Excretion • Altered drug elimination is the most common cause of adverse PK DDIs • GI absorption • Drug binding in GI tract • Alterations in GI motility • Alterations in GI pH • Cytochrome P450 • Induction or inhibition • Transport proteins • Induction or inhibition • Plasma protein binding • ? clinical significance P-glycoprotein (PGP): an efflux transporter Figure reproduced with permission from BioMed Central (http://www.biomedcentral.com): Edwards G. Filaria J. 2003;2(Suppl 1):S8. Drug Interaction Mechanisms (continued) Pharmacokinetic Interactions • GI absorption • Drug binding in GI tract • Alterations in GI motility • Alterations in GI pH • Plasma protein binding • Not clinically significant • Cytochrome P450 (CYP) • Induction or inhibition • Transport proteins (P-glycoprotein [PGP]) • Induction or inhibition 2 2/24/2014 Cytochrome P450 (CYP) Enzymes Human CYP CYP Family Subfamily Gene 1 A B 2 C 3 D E A 2 6 8 9 19 6 1 4 Clopidogrel Tamoxifen Macrolides, Azole antifungals Analysis of Arizona Medicaid Claims 16 Drug Combinations Identified Prescription Claims N = 1,723,924 • Collapse to patient level Persons N = 38,418 Who Prescribes Drug-Drug Interactions? Potential Drug-Drug Interactions by the Same Prescriber 70 60 50 40 30 20 10 0 Overall lapping days supply Potential Drug-Drug Interactions N = 25,553 • 67-year-old woman • Diagnosed with pneumonia after mitral valve repair • Developed the following on electrocardiogram... Past Medical History •Chronic atrial fibrillation •Heart failure •Hypertension •Hypothyroidism •Obesity Medications New medications: •Amiodarone •Levofloxacin Case adapted from: Proc (Bayl Univ Med Cent). 2006;19(4):345-6. Usually Avoid This Combination Amiodarone-Levofloxacin Risk Factors for TdP • Additive risk of QTc • Concomitant QTc-prolonging drugs prolongation • Potentially fatal • Data limited regarding arrhythmogenic risk of drugs alone or in combination • Female • Advancing age • Cardiac disease • Bradycardia • Familial history long QT syndrome • Electrolyte disturbances (e.g., low K+, Mg++, Ca++) QTc=rate-corrected QT interval on electrocardiogram; TdP=torsades de pointes 3 2/24/2014 Prolonged QT Risk Groups Risk of Torsades • Disopyramide • Procainamide • Quininidine • • • • Amiodarone Dofetilide Ibutilide Sotalol • Ciprofloxacin • Flecainide • • • • Gemifloxacin Levofloxacin Moxifloxacin Ofloxacin • 77-year-old woman • Presented with episodes of • Azithromycin • Clarithromycin • Erythromcyin QT drug lists by risk groups. Arizona Center for Education and Research on Therapeutics. Available at: http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm Warfarin-NSAID Past Medical History •Aortic valve replacement •Atrial fibrillation •Heart failure •Hypertension •Ischemic heart disease Conditional Risk of Torsades Possible Risk of Torsades Usually Avoid This Combination Case adapted from: Med J Aust. 1996;164(11):700-1. Usually Avoid This Combination Warfarin-NSAID (continued) • Acetaminophen or opioids preferred • Additive risk of bleeding • Limit acetaminophen & monitor • Some NSAIDs may also alter warfarin PK • Considerable increased risk of GI bleeding1 • 13-fold higher risk hospitalization for hemorrhagic PUD vs. neither drug; 4-fold higher risk with either drug alone • Co-prescribing common despite vomiting bright red blood and passing bloody stools • INR 2.1 (target 2.5-3.5) • Severe dyspnea due to aspiration • Expired from hypotension and multisystem failure Medications Chronic medications: •Warfarin •Furosemide •Lisinopril •Metoprolol New medication: •Ibuprofen (OTC) risks2,3 • Most common among top 25 clinically significant outpatient DDIs (242.7 per 1,000 warfarin recipients) • COX-2 inhibitors • No conclusive evidence for lower risk • Aspirin • Antiplatelet aspirin therapy increases minor bleeding risk • If combined use necessary • Monitor for bleeding • Consider prophylaxis for NSAID-associated GI injury 1) Shorr et al. Arch Intern Med. 1993;153(14)1665-70. 2) Malone et al. J Am Pharm Assoc (2003). 2004;44(2):142-51. 3) Malone et al. Am J Health Syst Pharm. 2005;62(19):1983-91. Take Precautions with This Combination Warfarin-Carbamazepine • Carbamazepine induces warfarin metabolism • The warfarin dose was likely previously increased to adjust for enzyme induction • Stopping the enzyme inducer would increase the warfarin concentration • The warfarin dose would be then excessive if not adjusted • Consider effects of stopping the precipitant drug – generally not detected by software Take Precautions with this Combination Carbamazepine-Clarithromycin • Clarithromycin inhibits carbamazepine metabolism by CYP3A4 • Consider alternatives • Azithromycin or non-macrolide depending on infection and susceptibilities • If combined use necessary, adjust and monitor • Temporarily decrease carbamazepine dosage (30%-50%) and monitor concentrations • Warn patients of toxicity symptoms 4 2/24/2014 • 45-year-old postmenopausal woman • Underwent surgery, chemotherapy, and radiation therapy, followed by 6 months tamoxifen • Pharmacogenetic testing for CYP2D6: extensive metabolizer • Developed recurrence of depressive symptoms Past Medical History •ER+ invasive breast cancer •Major depressive disorder Medications Chronic medications: •Tamoxifen Take Precautions with this Combination Tamoxifen-Fluoxetine • Fluoxetine inhibits conversion of prodrug tamoxifen by CYP2D6 to its primary active metabolite • Concern regarding increased risk breast cancer recurrence • Alternative antidepressants • Citalopram, sertraline, and venlafaxine do not significantly inhibit CYP2D6 • Bupropion, duloxetine, and paroxetine also inhibit CYP2D6 • Reasonable to avoid known CYP2D6 inhibitors based on current data Case adapted from: Am J Psychiatry. 2008;165(10):1251-5. Past Medical History •Hypertension •Hyperlipidemia Medications Chronic medications: •Simvastatin •Lisinopril •Aspirin New medication: •Itraconazole • 74-year-old man • Started treatment for toenail infection • 3 weeks later, lower extremity pain while golfing • Pain progressed to upper extremities and neck, urine turned brown • CK 22,800,000 U/L (reference range: 32-267) Usually Avoid this Combination Simvastatin-Itraconazole • Itraconazole inhibits simvastatin metabolism by CYP3A4 • Antifungal alternatives • Consider terbinafine (not CYP3A4 inhibitor) or ciclopirox nail lacquer (not absorbed) • Avoid azole antifungals (inhibit CYP3A4) • Hold simvastatin (short-term) • NOT in unstable angina or immediately post-MI • Statin alternatives • Consider fluvastatin, rosuvastatin or pravastatin (not CYP3A4 substrates) • Avoid lovastatin and atorvastatin (to a lesser extent) CK=creatine kinase Case Adapted from: Ann Pharmacother. 2006;40(4):753-7. Usually Avoid this Combination Simvastatin-Amiodarone Clinically Relevant Interactions • Amiodarone inhibits simvastatin metabolism by CYP3A4 • Statin alternatives • Consider fluvastatin, rosuvastatin, pravastatin (not Object Medications Precipitant Medication DDI-Specific Hospitalization: Odds Ratio 95% CI DDI-Specific Medical Outcome: Odds Ratio 95% CI Total Healthcare Cost Difference in Follow up Period Amiodarone and/or Sotalol Macrolides or quinolones 1.13 (0.94-1.36) 1.52 (1.40-1.66) $1923 ($1348 - $2497) Amiodarone Macrolides 1.21 (0.60-2.46) 1.84 (1.32-2.55) $2784 ($1509 - $4059) Amiodarone Quinolones 1.16 (0.94-1.42) 1.57 (1.43-1.74) $2756 ($2011 - $3500) Carbamazepine Azole Antifungals 3.00 (1.09-8.25) 2.40 (1.57-3.67) $785 ($382 - $1187) Carbamazepine Macrolides 10.00 (1.28-78.12) 2.00 (1.23-3.27) $1181 ($722 - $1640) metabolized by CYP3A4) • Avoid lovastatin and atorvastatin (to a lesser extent) • If combined use necessary • Maximum simvastatin dose: 20 mg/day • Warn patients to report muscle pain, tenderness, or weakness Risk Factors for Rhabdomyolysis • Advanced age (>65 years) •Uncontrolled hypothyroidism •Renal impairment 5 2/24/2014 Clinically Relevant Interactions Object Medication Precipitant Medication DDI-Specific Hospitalization: Odds Ratio 95% CI DDI-Specific Medical Outcome: Odds Ratio 95% CI Warfarin Interactions Object Medication Total Healthcare Cost Difference in Follow up Period Amiodarone 2.26 (1.89-2.70) 2.24 (2.02-2.48) Warfarin Sulfamethoxazole 3.40 (2.53-4.57) 2.87 (2.42-3.41) Metronidazole 4.72 (3.22-6.91) 7.70 (6.03-9.83) 2.37 (1.70-3.31) 3.62 (2.90-4.53) 1.41 (1.00-1.99) Azole Antifungals 2.00 (0.50-8.00) 1.33 (0.46-3.84) $994 ($810 - $1177) Lovastatin or Simvastatin Macrolides - 9.00 (1.1471.04) $872 ($781 - $962) Warfarin Lithium NSAIDS 2.00 (0.37-10.92) 3.22 (1.90-5.47) $681 ($491 - $870) Warfarin Warfarin •Pharmacodynamic interaction: additive • > 65 years old •Patient Management: • Hepatic impairment • Co-administration of nitrates with sildenafil may be appropriate under certain conditions. • Severe renal impairment Drug ACC/AHA Recommendations for nitrate administration sildenafil 24 hours tadalafil 48 hours vardenafil 24 hours (not in guideline) $1656 ($1382 - $1930) $3252 ($2869 $3634) $4533 ($4043 $5022) $6130 ($5377 $6883) 1.67 (1.39-2.02) $467 ($288 - $646) Warfarin Statins 1.61 (1.37-1.89) 1.83 (1.67-2.00) $515 ($424 - $606) Warfarin NSAIDS 3.26 (2.49-4.26) 2.45 (2.09-2.87) $1940 ($1763 - $2117) • Proposed mechanism of interaction: • • • • •Predisposing factors: Fluconazole or Voriconazole Fenofibrate or Gemfibrozil Total Healthcare Cost Difference in Follow up Period Statins and Gemfibrozil (Fibrates) hypotensive effects •flushing, dizziness, headache, death DDI-Specific Medical Outcome: Odds Ratio 95% CI DDI-Specific Hospitalization: Odds Ratio 95% CI Warfarin Lovastatin or Simvastatin Other Interactions to Avoid Sildenafil and Nitrates Precipitant Medication Displacement of protein binding Atypical enzyme interaction Direct action on myocytes Interference with multiple drug resistance protein (MDRP) • Risk of co-administration: Severe myopathy, Rhabdomyolysis, Acute renal failure • Evidence: • PK studies and reviews of FDA Adverse Event Reporting databases Overall incidence is rare but serious • • Risk is higher for gemfibrozil than fenofibrate (15x) Simvastatin has highest reporting rate (4/100,000) • • >80% of reported rhabdomyolysis cases resulted in hospitalization for renal failure Colchicine-Clarithromycin Summary • Colchicine is substrate for CYP3A4 and PGP • Clarithromycin is potent inhibitor of both • FDA database: 60 fatalities (as of 2010) • Retrospective case series of 88 patients • Drug interaction knowledge is poor among • 9 expired • Adverse outcomes • Pancytopenia • GI effects: diarrhea, N/V, pain • Myopathy • Multi-organ failure • Onset • Time to symptoms – approximately 4 days • Time to death (< 2 weeks) health professionals • Many DDIs result from multiple prescribers – but not all • Interactions can be harmful • Hospitalization • Morbidity • Costs 6 2/24/2014 RED Flag Medications • Warfarin • Macrolide antibiotics • Clarithromycin / erythromycin • Azole antifungals • Anti-epileptic medications • Amiodarone 7 Evidence-based Treatment of Hypertension and High Blood Cholesterol: Update on New Guidelines ACPE # 0008-0000-14-007-L01-P (1 contact hour – knowledge based) Joseph Saseen, PharmD, FCCP, BCPS, CLS Professor and Vice Chair Department of Clinical Pharmacy Professor, Department of Family Medicine CU schools of Pharmacy and Medicine Learning Objectives 1. Describe the process for developing new hypertension, high blood cholesterol, and assessment of cardiovascular risk guidelines. 2. Review new guideline recommendations for the treatment of patients with hypertension and dyslipidemia. 3. List patient specific blood pressure goals and recommended treatments for patients with hypertension. 4. Identify patients who are eligible for statin-based therapy and describe how they should be treated. 2/10/2014 Evidence-Based Treatment of Hypertension and High Blood Cholesterol: Update on New Guidelines Disclosure Statement – no financial relationships to disclose Joseph Saseen Statement of Disclosure Saturday, February 22, 2014 Joseph Saseen, Pharm.D., FASHP, FCCP, BCPS Professor and Vice Chair, Department of Clinical Pharmacy University of Colorado Anschutz Medical Campus I have no relevant financial relationships with commercial interests pertaining to the content presented in this program. Learning Objectives Patient Cases • Describe the process for developing new hypertension, high blood cholesterol, and assessment of cardiovascular risk guidelines • Review new guideline recommendations for the treatment of patients with hypertension and dyslipidemia • List patient specific blood pressure goals and recommended treatments for patients with hypertension • Identify patients who are eligible for statin-based therapy and describe how they should be treated 50-year-old African American man has hypertension. His a smoker. Despite lifestyle modifications for 6 months, BP is 156/96 mm Hg. TC = 205 mg/dL, HDL-C = 40 mg/dL, LDL-C = 120 mg/dL, triglycerides = 225 . No chronic medications. 70-year-old woman with hypertension, CHD (s/p MI), dyslipidemia. Adherent with atorvastatin 20 mg daily, carvedilol 25 mg twice daily and lisinopril 40 mg daily. BP is 144/90 mm Hg. No fasting lipid panel available. 60-year-old white man with hypertension and type 2 diabetes. Adherent with amlodipine 10 mg daily, HCTZ 25 mg daily, and ezetimibe/simvastatin 10/10 mg daily. BP is 128/78 mm Hg, LDL-C is 65 mg/dL. How should these patients be treated? 2004: NCEP ATP III Goals Risk Category High Risk: CHD or CHD Equivalent (10-y risk > 20%) Moderately High Risk: 2+ Risk Factors (10-y risk 10-20%) Moderate Risk: 2+ Risk Factors LDL-C Goal Non-HDL-C Goal Initiate TLC Consider Drug Treatment (mg/dL) (mg/dL) (mg/dL) (mg/dL) <100 <130 100 100 <100: for high risk patients Optional Goal: <70* <100 <130 Optional Goal: <160 130 <100 <130 <160 130 100 – 129: consider to achieve LDL-C goal of <100 130 160 160 190 160 – 189: LDL-C Lowering Drugs Optional National Heart Lung and Blood Institute: Systematic Evidence Reviews in Development Director's Corner Message: NHLBI adopts new collaborative partnership model for clinical practice guidelines development Draft Finished Federal Review Expert Review Advisory Council HHS Clearance Partnerships Formed Blood Pressure Partner Release Completed Completed Completed Completed Pending Ongoing Cholesterol Completed Completed Completed Completed Pending Ongoing ACC/AHA Obesity Completed Completed Completed Completed Pending Ongoing ACC/AHA Lifestyle Completed Completed Completed Completed Pending Ongoing ACC/AHA Risk Assessment Completed Completed Completed Completed Pending Ongoing ACC/AHA (10-y risk < 10%) Lower Risk: 0-1 Risk Factors <160 (10-y risk < 10%) * For Very High Risk patients <190 NCEP ATP III =National Cholesterol Education Program. Adult Treatment Panel III guidelines. TLC= Therapeutic Lifestyle changes Grundy S, et al. Circulation. 2004;110:227-239. Last Updated November 2013 http://www.nhlbi.nih.gov/guidelines/indevelop.htm#status 1 2/10/2014 Clinical Practice Guidelines for Prevention (November 12, 2013) 2013 ACC/AHA Guidelines Focus Three Critical Questions • What evidence supports LDL-c goals for secondary prevention? • What evidence supports LDL-c goals for primary prevention? • What is the impact of the major cholesterol drugs on efficacy/safety in the populations? http://networking.americanheart.org/blogs/6/785 What is new in the 2013 ACC/AHA Blood Cholesterol Guideline? Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. ASCVD Statin Benefit Groups Heart healthy lifestyle habits are the foundation of ASCVD prevention. In individuals not receiving cholesterol-lowering drug therapy, recalculate estimated 10-y ASCVD risk every 4-6 y in individuals aged 40-75 y without clinical ASCVD or diabetes and with LDL–C 70-189 mg/dL. Yes Adults age >21 y and a candidate for statin therapy Yes Clinical ASCVD No The panel makes no recommendations for or against specific LDL-C or non-HDL-C targets for primary or secondary prevention of ASCVD Yes High Daily dose lowers LDL-C by approx. ≥50% Moderate Daily dose lowers LDL-C by approx. 20% to <50% Age >75 y OR if not candidate for high-intensity statin Moderate-intensity statin High-intensity statin (Moderate-intensity statin if not candidate for high-intensity statin) LDL-C ≥190 mg/dL Definitions of High- and Moderate-Intensity Statin Therapy Age ≤75 y High-intensity statin (Moderate-intensity statin if not candidate for high-intensity statin) No Yes Diabetes Type 1 or 2 Age 40-75 y Yes Moderate-intensity statin Estimated 10-y ASCVD risk ≥7.5%* High-intensity statin No Estimate 10-y ASCVD Risk with Pooled Cohort Equations* ≥7.5% estimated 10-y ASCVD risk and age 40-75 y Yes Moderate-to-High Intensity Statin No ASCVD prevention benefit of statin therapy may be less clear in other groups In selected individuals, consider additional factors influencing ASCVD risk‡ and potential ASCVD risk benefits and adverse effects, drug-drug interactions, and patient preferences for statin treatment Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. 4 Statin Benefit Groups Clinical ASCVD LDL-C ≥190 mg/dL Diabetes Type 1 or 2 Age 40-75 y ≥7.5% estimated 10-y ASCVD risk and age 40-75 y Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. Clinical Atherosclerotic Cardiovascular Disease (ASCVD) • Coronary heart disease (CHD) – Acute Coronary Syndromes – History of myocardial infarction – Stable or unstable angina – Coronary revascularization • Symptomatic carotid artery disease – Stroke – TIA presumed to be of atherosclerotic origin • Peripheral arterial disease or revascularization Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. 2 2/10/2014 ACC/AHA 2013 Blood Cholesterol Guideline: ACC/AHA 2013 Blood Cholesterol Guideline: ASCVD ASCVD Class I Recommendations Level of Evidence High-Intensity statin therapy should be initiated or continued as first line therapy in men and women for < 75 years of age who have clinical ASCVD, unless contraindicated A In individuals with clinical ASCVD in whom high-Intensity statin therapy would otherwise be used, when high-intensity statin therapy is contraindicated or when characteristics predisposing to statin-associated adverse effects are present, moderate-intensity statin should be used as the second option if tolerated A Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. Level of Evidence In individuals with clinical ASCVD >75 years of age, it is reasonable to evaluate the potential for ASCVD risk-reduction benefit and for adverse effects, DDIs, and to consider patient preferences, when initiating a moderate to high-intensity statin. It is reasonable to continue statin therapy in those who are tolerating it B Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. ACC/AHA 2013 Blood Cholesterol Guideline: Statin Intensity High-Intensity Moderate-Intensity Low-Intensity Daily dose lowers LDL–C on average, by ~ ≥ 50% Daily dose lowers LDL–C on average, by ~ 30 to <50% Daily dose lowers LDL–C on average, by <30% Atorvastatin (40)–80 mg Atorvastatin 10 (20) mg Rosuvastatin 20 (40) mg Rosuvastatin (5) 10 mg Simvastatin 20–40 mg Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2–4 mg Class IIa Recommendation Simvastatin 10 mg Pravastatin 10–20 mg Lovastatin 20 mg Fluvastatin 20–40 mg Pitavastatin 1 mg 4 Statin Benefit Groups Clinical ASCVD LDL-C ≥190 mg/dL Diabetes Type 1 or 2 Age 40-75 y ≥7.5% estimated 10-y ASCVD risk and age 40-75 y Specific statins and doses are noted in bold that were evaluated in randomized controlled trials. Statins and doses that are approved by the U.S. FDA but were not tested in the RCTs reviewed are listed in italics. Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. ACC/AHA 2013 Blood Cholesterol Guideline: LDL-C ≥ 190 mg/dL Class I Recommendations Adults ≥21 years of age with primary LDL–C ≥190 mg/dL should be treated with statin therapy (10-year ASCVD risk estimation is not required): • Use high-intensity statin therapy unless contraindicated • For individuals unable to tolerate high-intensity statin therapy, use the maximum tolerated statin intensity Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. Level of Evidence B National Lipid Association: Familial Hypercholesterolemia • Familial hypercholesterolemias (FH) are genetic defects resulting in severe cholesterol elevations and increased risk of premature CHD • Prevalence of FH is 1 in 300 to 500 – Homozygous FH affects 1 in 1,000,000 • Aggressive lipid lowering is necessary – Target LDL-C reduction of at least 50% – Greater LDL-C reductions may be necessary for FH patients with other CHD risk factors Journal of Clinical Lipidology 2011;5:133–140. 3 2/10/2014 ACC/AHA 2013 Blood Cholesterol Guideline: LDL-C ≥ 190 mg/dL Class IIa Recommendation Level of Evidence For individuals ≥21 years of age with an untreated primary LDL–C ≥190 mg/dL, it is reasonable to intensify statin therapy to achieve at least a 50% LDL–C reduction. B Class IIb Recommendation C Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. LDL-C ≥190 mg/dL Diabetes Type 1 or 2 Age 40-75 y ≥7.5% estimated 10-y ASCVD risk and age 40-75 y Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. ACC/AHA 2013 Blood Cholesterol Guideline: Primary Prevention in DM and LDL-C 70-189 mg/dL Class I Recommendation Level of Evidence Moderate-Intensity statin therapy should be initiated or continued for adults 40 to 75 years of age with DM A Class IIa Recommendation Level of Evidence High-Intensity statin therapy is reasonable for adults age 40 to 75 years of age with DM with a 10 year ASCVD risk > 7.5% unless contraindicated B In adults with DM less than 40 or > 75 years of age it is reasonable to evaluate for the potential ASCVD benefits and for adverse effects, DDIs, and to consider patient preference when deciding to initiate, continue, or intensify statin therapy C Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk • Based on the Pooled Cohort Equations • Predicts 10-year risk (and lifetime risk) of: – Nonfatal/Fatal Myocardial Infarction – Nonfatal/Fatal Stroke • Information required: – Age, sex, race, total cholesterol, HDL-C, systolic blood pressure, blood pressure lowering medication use, diabetes status, smoking status http://my.americanheart.org/cvriskcalculator 48-year-old African American man with type 2 diabetes. Nonsmoker. BP is 136/86 mm Hg on antihypertensive drug therapy. TC = 200 mg/dL, HDL-C = 45 mg/dL, not on a statin. 10‐Year and Lifetime ASCVD Risks 69.0 70.0 Clinical ASCVD Level of Evidence For individuals ≥21 years of age with an untreated primary LDL–C ≥190 mg/dL, after the maximum intensity of statin therapy has been achieved, addition of a nonstatin drug may be considered to further lower LDL–C. Evaluate the potential for ASCVD risk reduction benefits, adverse effects, drug-drug interactions, and consider patient preferences. 80.0 4 Statin Benefit Groups 4 Statin Benefit Groups Clinical ASCVD LDL-C ≥190 mg/dL Diabetes Type 1 or 2 Age 40-75 y ≥7.5% estimated 10-y ASCVD risk and age 40-75 y Predicted Risk (%) 60.0 50.0 40.0 30.0 20.0 16.7 3.5 10.0 5.0 0.0 Your 10‐Year ASCVD 10‐Year ASCVD Risk Risk (%) (%) for Someone Your Age with Optimal Risk Factor Levels (shown above in column E) http://my.americanheart.org/cvriskcalculator Your Lifetime ASCVD Lifetime ASCVD Risk Risk* (%) (%) for Someone at Age 50 with Optimal Risk Factor Levels (shown above in column E) Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. 4 2/10/2014 ACC/AHA 2013 Blood Cholesterol Guideline: Major CV Events at Different Levels of Risk in Primary Prevention Baseline Risk Categories Events (% per year) Statin/ Control/ more statin Less (n=1904) (n=2425) < 5% 148 (0.35%) Risk ratio & 95% CI 229 (0.53%) 0.61 (0.45-0.81) > 5% to < 10% 487 (1.02%) 716 (1.53%) 0.66 (0.57-0.77) > 10% to < 20% 854 (2.52%) 1003 (2.98%) 0.82 (0.72-0.93) > 20% to < 30% 294 (4.40%) 351 (5.28%) 0.81 (0.65-1.01) > 30% 121 (7.29%) 126 (8.16%) 0.83 (0.58-1.18) Subtotal 1904 (1.44%) 2425(1.84%) 0.75 (0.70-0.80) 0.6 0.8 1.0 Statin/more statin 1.2 1.4 Control/ Less Cholesterol Treatment Trialists Collaboration. Lancet 2012;380:581-90. Primary Prevention no DM and LDL-C 70-189 mg/dL Class I Recommendations The pooled cohort equations should be used to estimate 10 year ASCVD risk for individuals with and LDL-C between 70 to 189 mg/dL without clinical ASCVD to guide initiation of statin therapy for primary prevention B Adults age 40 to 75 years of age without clinical ASCVD or DM and a 10 yr ASCVD risk > 7.5% should be treated with a moderate to high intensity statin therapy A Class IIa Recommendations B Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. Assess medication and lifestyle adherence Fasting lipid panel Primary Prevention no DM and LDL-C 70-189 mg/dL In adults with LDL–C <190 mg/dL who are not otherwise identified in a statin benefit group, or for whom after quantitative risk assessment a risk-based treatment decision is uncertain, additional factors may be considered to inform treatment decision making. In these individuals, statin therapy for primary prevention may be considered after evaluating the potential for ASCVD risk reduction benefits, adverse effects, drug-drug interactions, and discussion of patient preferences. Level of Evidence Reasonable to offer moderate intensity statin to adults 40 to 75 years of age with LDL-C 70-189 mg/dL, without clinical ASCVD or DM and a 10 year ASCVD risk of 5 to < 7.5% ACC/AHA 2013 Blood Cholesterol Guideline: Class IIb Recommendations Level of Evidence Anticipated therapeutic response? Level of Evidence C • Additional Risk Factors: – LDL-C > 160 mg/dL or genetic hyperlipidemia; Family hx ASCVD in father < 55 yrs of age or mother < 65 years of age; hsCRP > 2 mg/dL, CAC score > 300 Agatston units or > 75 percentile for age, sex, and ethnicity; ABI < 0.9; or lifetime risk of ASCVD Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. ACC/AHA 2013 Blood Cholesterol Guideline: Safety Recommendations • Moderate-intensity statin therapy should be used in individuals in whom high-intensity statin therapy would otherwise be recommended when characteristics predisposing them to statin associated adverse effects are present Yes Reinforce continued adherence Follow-up 3-12 mo • • Indicators of anticipated therapeutic response and adherence to selected statin intensity: High-intensity statin therapy† reduces LDL–C approx. ≥50% from the untreated baseline Moderate-intensity statin therapy reduces LDL–C approx. 30% to <50% from the untreated baseline. No Less-than-anticipated therapeutic response Yes Anticipated therapeutic response? No Intolerance to recommended dose of statin therapy Yes Management of statin intolerance No Reinforce improved adherence Increase statin intensity OR Consider addition of nonstatin drug therapy Reinforce medication adherence Reinforce adherence to intensive lifestyle changes Exclude secondary causes of hypercholesterolemia Follow-up 4-12 wk & thereafter as indicated Follow-up 4-12 wk Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. ACC/AHA 2013 Blood Cholesterol Guideline: Characteristics Predisposing Individuals to Statin Adverse Effects • • • • Multiple or serious comorbidities Previous statin intolerance or muscle disorders Unexplained ALT elevations >3 times ULN Patient characteristics or concomitant use of drugs affecting statin metabolism • >75 years of age Additional characteristics: History of hemorrhagic stroke and Asian ancestry Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. 5 2/10/2014 ACC/AHA 2013 Blood Cholesterol Guideline: ACC/AHA 2013 Blood Cholesterol Guideline: Statin Safety Recommendations Statin Safety Recommendations • Individuals receiving statin therapy should be evaluated for new-onset diabetes mellitus and those who develop diabetes mellitus during statin therapy should engage in CV risk reduction lifestyle modifications and continue statin therapy to reduce their risk of ASCVD Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. ACC/AHA 2013 Blood Cholesterol Guideline: Lipid-Lowering Therapies Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, pitavastatin, rosuvastatin, simvastatin) Bile acid sequestrants (colesevelam, cholestyramine, colestipol) Nicotinic acid Fibric acid derivatives (gemfibrozil, fenofibrate) Cholesterol absorption inhibitor (ezetimibe) Omega-3 fatty acids (Rx strength) • Serum creatine kinase (CK) values should not be routinely measured in individuals receiving statin therapy • During statin therapy, it is reasonable to measure CK in individuals with muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or generalized fatigue • Decreasing the statin dose may be considered when 2 consecutive values of LDL–C levels are <40 mg/dL Nonstatin Drugs LDL-C HDL-C TG 18-63% 5-15% 7-30% 15-30% 3-5% 0 or 5-25% 15-35% 20-50% 5-20% or 10-20% 20-50% 18% 1% 7% ? 9% 45% The panel could find no data supporting the routine use of nonstatin drugs combined with statin therapy to reduce further ASCVD events • In individuals who are candidates for statin treatment but are completely statin intolerant, it is reasonable to use nonstatin cholesterollowering drugs that have been shown to reduce ASCVD events in RCTs if the ASCVD riskreduction benefits outweigh the potential for adverse effects. Executive summary of NCEP ATP III. JAMA. 2001; 285:2486-97; Crestor package insert. Astra-Zeneca, 2009; Zetia package insert. Merck/Schering-Plough Pharmaceuticals, 2009; Lovaza package insert. GlaxoSmithKline, 2009; Livalo package insert. Kowa Pharmaceuticals America, 2010. Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. ACC/AHA 2013 Blood Cholesterol Guideline: Additional Recommendations • The panel makes no recommendations regarding the initiation or discontinuation of statins in patients with NYHA Class II-IV ischemic systolic heart failure or in patients on maintenance hemodialysis Parting Thoughts…. • Identified 4 statin benefit groups • Statin intensity is clinically important • High-priority research areas to evaluate evidence gaps: – Primary prevention in patients > 75 years – Goals vs fixed-dose statin therapy – Low-intensity statin plus nonstatin in statinintolerant patients – New onset diabetes with statin therapy – Role of new and emerging drug therapies Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013. 6 2/10/2014 National Heart Lung and Blood Institute: Systematic Evidence Reviews in Development Director's Corner Message: NHLBI adopts new collaborative partnership model for clinical practice guidelines development Draft Finished Federal Review Expert Review Advisory Council HHS Clearance Partnerships Formed Blood Pressure Partner Release Completed Completed Completed Completed Pending Ongoing Cholesterol Completed Completed Completed Completed Pending Ongoing ACC/AHA Obesity Completed Completed Completed Completed Pending Ongoing ACC/AHA Lifestyle Completed Completed Completed Completed Pending Ongoing ACC/AHA Risk Assessment Completed Completed Completed Completed Pending Ongoing ACC/AHA THE WRITING ON THE WALL….. COMMENTARY JNC 8 Transmogrified Barry J. Matterson, MD, MBA J Clin Hypertens 2013;10:704. Last Updated November 2013 http://www.nhlbi.nih.gov/guidelines/indevelop.htm#status SO WHAT CAME NEXT….. Tuesday December 17, 2013 Clinical Practice Guidelines for the Management of Hypertension in the Community A Statement by the American Society of Hypertension (ASH) and the International Society of Hypertension (ISH) Wednesday December 18, 2014 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) J Hypertens 2014 Jan;32(1):3-15 JNC 8 Original Critical Questions • Among adults with hypertension, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes? • Among adults, does treatment with an antihypertensive pharmacological therapy to a specified BP goal lead to improvements in health outcomes? • In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? http://www.nhlbi.nih.gov/guidelines/cvd_adult/background.htm JAMA. doi:10.1001/jama.2013.284427 ASH/ISH : General Recommendations Age < 80 years: • Goal BP is usually <140/90 mm Hg • Past guidelines recommended <130/80 mm Hg for diabetes, chronic kidney disease (CKD), and coronary artery disease; however, evidence to support this lower target in patients with these conditions is lacking • Some experts still recommend <130/80 mm Hg if albuminuria is present in CKD “JNC 8” Report: General Recommendations Age ≥ 60 years: • initiate pharmacologic treatment at BP ≥150/90 mmHg and treat to a goal <150/90 mm Hg (Strong Recommendation – Grade A) • if pharmacologic treatment results in lower achieved SBP (e.g., <140 mm Hg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted. (Expert Opinion – Grade E) Age ≥ 80 years: • Threshold for starting and target for treatment is ≥150/90 mmHg (if CKD or diabetes, consider <140/90 mm Hg) Age < 60 years: • initiate pharmacologic treatment to lower BP at ≥140/90 mmHg and treat to a goal BP<140/90 mmHg (DBP: For ages 30-59 years, Strong Recommendation – Grade A. DBP: For ages 18-29 years. SBP: Expert Opinion – Grade E) J Hypertens 2014 Jan;32(1):3-15 JAMA. doi:10.1001/jama.2013.284427 7 2/10/2014 “Evidence Supporting a SBP Goal <150 mm Hg in Patients Aged ≥60 Years: The Minority View” ASH/ISH Guideline Jackson T. Wright Jr., MD, PhD; Lawrence J. Fine, MD, DrPH; Daniel T. Lackland, PhD; Gbenga Ogedegbe, MD, MPH, MS; and Cheryl R. Dennison Himmelfarb, PhD, RN, ANP • Minority of the JNC 8 panel: – Disagreed with increasing SBP goal from 140 to 150 mm Hg in persons aged ≥60 yrs without DM or CKD – Believed evidence was insufficient to justify a change – Concerned increasing the goal may cause harm by increasing CV risk and partially undoing the remarkable progress in reducing CV mortality in Americans > 60 yrs – Endorsed SBP goal <150 mm Hg in frail patients ≥80 yrs • SBP goal <140 mm Hg for patients <80 yrs would be in line with guidelines from Europe, Canada, ACC-AHA, United Kingdom, and ASH-ISH Ann Intern Med. Published online 14 January 2014 doi:10.7326/M13-2981 ASH/ISH: Drug Therapy for Hypertension with Other Conditions J Hypertens 2014 Jan;32(1):3-15 “JNC 8” Report First Drug Diabetes Mellitus Chronic Kidney Disease ACEI, or ARB (Note: In Black patients CCB or Thiazide is acceptable) ACEI, or ARB (Note: In Black patients good evidence with ACEI CAD Beta-blocker plus ACEI or ARB Prior Stroke ACEI or ARB Heart Failure ACEI (or ARB) plus beta-blocker plus diuretic plus spironolactone Regardless of blood pressure if symptomatic J Hypertens 2014 Jan;32(1):3-15 Common Themes…. JAMA. doi:10.1001/jama.2013.284427 Antihypertensive therapy reduces risk of CV events in patients with elevated BP! Beta-blocker after ACEi or ARB, CCB, and thiazide unless coronary artery disease or systolic heart failure is present 8 2/10/2014 Thiazide diuretics Differences and Omissions…. Beta-blockers Angiotensin Receptor Blockers Other Antihypertensives Calcium Channel Blockers ACE Inhibitors Preferred Combinations Possible but less well tested Useful Combination with limitations Not Recommended Journal of Hypertension 2013, 31:1281–1357 KDIGO: Albuminuria Influences Treatment • Chronic Kidney disease, non-dialysis patients Urine Albumin Excretion per 24 hrs < 30 mg BP Goal (mm Hg) ≤140/90 Treatment Not specified 30 to 300 mg ≤130/80 ACE-I or ARB > 300 mg ≤130/80 ACE-I or ARB Recommendations & Level of Evidence ADA: Hypertension/Blood Pressure Control Goals • Treat to a systolic BP goal of < 140 mmHg (B) • Lower systolic targets (e.g., < 130 mmHg), may be appropriate for certain patients (e.g., younger), if achieved without undue treatment burden (C) • Treat to a diastolic BP < 80 mmHg (B) – Same suggestions and recommendations provided for patients with diabetes and without, but different cited level of evidence Kidney International Supplements (2012) 2, 341–342 Parting Thoughts… • General goal of <140/90 mm Hg for most patients • Beta-blockers are not first-line agents • Race advocated to influence selection of drug therapy • Many similarities with new guidelines, but significant yet subtle differences Diabetes Care 2013;36 (Suppl 1): s11-s66. Patient Cases 50-year-old African American man has hypertension. His a smoker. Despite lifestyle modifications for 6 months, BP is 156/96 mm Hg. TC = 205 mg/dL, HDL-C = 40 mg/dL, LDL-C = 120 mg/dL, triglycerides = 225 . No chronic medications. 70-year-old woman with hypertension, CHD (s/p MI), dyslipidemia. Adherent with atorvastatin 20 mg daily, carvedilol 25 mg twice daily and lisinopril 40 mg daily. BP is 144/90 mm Hg. No fasting lipid panel available. 60-year-old white man with hypertension and type 2 diabetes. Adherent with amlodipine 10 mg daily, HCTZ 25 mg daily, and ezetimibe/simvastatin 10/10 mg daily. BP is 128/78 mm Hg, LDL-C is 65 mg/dL. How should these patients be treated? 9 2/10/2014 Challenges "Drugs don't work in patients who don't take them." Former U.S. surgeon general C. Everett Koop http://usatoday30.usatoday.com/news/health/2007-03-28-taking-medicine_N.htm 10
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