N P S PPR National Prescribing Service Ltd No. 8 May 2000 Prescribing Practice Review Management of Heart Failure Medication review for your patients with heart failure Patients with chronic conditions, such as heart failure, require regular medication review. Medication history Ask about pattern of medication use Ask about prescription drugs, over-thecounter and complementary medicines Non-compliance with drug therapy is an important cause of treatment failure. Consider drugs that may exacerbate heart failure; Ask about perceived drug efficacy ▲ negative inotropic drugs such as verapamil and diltiazem How does the patient perceive their quality of life? Are symptoms controlled? ▲ antiarrhythmics other than amiodarone ▲ beta-blockers, as well as being used to treat heart failure, may exacerbate the condition ▲ NSAIDs and COX-2-selective NSAIDs2 ▲ preparations high in sodium, such as urinary alkalinisers ▲ complementary medicines containing willow bark. Problem identification Are there any untreated indications? ▲ confirm the diagnosis of heart failure and other co-existing diseases, eg atrial fibrillation ▲ consider if hypertension, hyperlipidaemia, arrhythmias and diabetes are controlled ▲ consider an audit of your medical records to check your patients taking digoxin for atrial fibrillation are also on warfarin. Have appropriate non-drug measures been instituted? Encourage patients to keep a symptom diary and a set of scales to monitor their daily weight. Weight gain may be an early sign of clinical deterioration1. Smoking cessation, good nutrition, salt and alcohol restriction should be addressed. Moderate regular exercise should be encouraged in patients with chronic stable heart failure1. Ask about non-pharmacological management Consider physical activity, fluid restriction in patients with congestion, sodium restriction and weight reduction (if applicable). Ensure the patient understands their condition and is able to monitor and report changes in symptoms. Vaccination against influenza and pneumococcus is recommended to reduce the risk of serious respiratory infection. Is this medication regimen the most appropriate for this patient? Is drug therapy optimal to achieve your treatment goal of improving prognosis and controlling symptoms and signs of heart failure? Is the patient taking an ACE inhibitor? ACE inhibitors alleviate symptoms and reduce mortality and risk of hospitalisation for heart failure. They are now recommended as first-line therapy for virtually all patients with clinical heart failure, unless there are specific contraindications to their use1,2,3 (see page 3). Patients with contraindications to the use of ACE inhibitors may benefit from other vasodilator therapy (eg hydralazine and isosorbide dinitrate)1-3. Consider specialist referral. Is diuretic therapy optimal? Diuretics should not be used alone in heart failure. If required, add to ACE inhibitors to help control congestive symptoms and signs1-3. Most patients with moderate to severe heart failure will require treatment with a loop diuretic (frusemide, bumetanide or ethacrynic acid). Thiazide diuretics are indicated for mild heart failure and are less effective in renal impairment and in the elderly. The addition of a thiazide to a loop diuretic may be used in severe heart failure with close monitoring3. Once good diuresis is obtained patients may be educated to adjust diuretic doses using daily weighing to monitor the response (if necessary). Would spironolactone be helpful in this patient? Low-dose spironolactone (25mg), when added to diuretic and ACE inhibitor therapy, can improve prognosis in patients with severe heart failure 6. Its benefits in patients with mild to moderate heart failure are not yet known. Monitor serum potassium frequently to avoid hyperkalaemia (see NPS News, Issue 9). Would the patient benefit from beta-blocker therapy? Some beta-blockers have been shown to improve prognosis in patients with mild to moderate heart failure. They are increasingly being used in combination with ACE inhibitors and diuretics in the treatment of chronic stable heart failure 1,4. Carvedilol is the only beta-blocker approved for treatment of heart failure in Australia. There is accumulating evidence that low dose metoprolol has similar effects however, it is not approved for this indication. Beta-blockers can be difficult to use in heart failure. To avoid complications, such as severe hypotension and bradycardia, treatment should be commenced at low doses and titrated carefully under specialist supervision1,2,4. Is digoxin indicated? Consider changes in evidence for digoxin Digoxin is indicated for use in heart failure in: 1. patients with atrial fibrillation 2. as a third-line treatment for patients in sinus rhythm who remain symptomatic despite optimal doses of ACE inhibitors and diuretics. Digoxin can alleviate symptoms however, it does not affect survival in this patient group8. Carefully titrate the dose according to age, serum, creatinine and serum digoxin levels to avoid toxicity. Any hypokalaemia should be corrected before commencing treatment. Can angiotensin II receptor antagonists be used in heart failure? To date there is no consistent evidence that angiotensin II receptor antagonists (eg candesartan, irbesartan, losartan, telmisartan) improve longterm survival in heart failure. They are not approved for the treatment of heart failure, but have been suggested as an alternative to ACE inhibitors in patients with a troublesome ACE inhibitor induced cough1,2. Alternatively, there is evidence that isosorbide dinitrate and hydralazine are effective. Table 1 - Doses of ACE inhibitors in heart failure (from Therapeutic Guidelines: Cardiovascular 3rd ed 2) Drug Brand names Starting Dose Target Maintenance Dose captopril* Acenorm, Capace, Capoten, Captohexal, DBL, Enzace, SBPA Amprace, Renitec Monopril Prinivil, Zestril Coversyl Accupril, Asig Ramace, Tritace Gopten, Odrik 6.25mg twice daily 50mg three times daily 2.5mg daily 5mg daily 2.5mg daily 2mg daily 2.5mg daily 1.25mg daily 0.5mg daily 10-20mg twice daily 20-40mg daily 20-40mg daily 4-8mg daily 20-40mg daily 5-10mg daily 2-4mg daily enalapril fosinopril lisinopril perindopril quinapril ramipril** trandolapril** * 2.5mg manufacturer’s recommended starting dose in sensitive patients, eg sodium depletion/high doses of diuretics. ** approved for heart failure post-MI only. 2 Is there an ongoing need for these drugs? Two questions need to be asked, are there mortality benefits for patients and have any drugs been initiated to treat adverse effects? Is the dose, frequency and formulation appropriate? Consider doses of ACE inhibitors ▲ angioedema during previous ACE inhibitor therapy ▲ pregnancy. Contraindications/precautions to the use of betablockers ▲ decompensated, severe heart failure ▲ reversible airways disease and chronic obstructive pulmonary disease Whenever possible use at doses which have demonstrated mortality benefits (see Table 1 for target doses) 1,2,3,5. With careful dose titration and follow-up high doses are achievable and well tolerated in most patients1,5. Monitor blood pressure, renal function and volume status. ▲ symptomatic bradycardia (< 50 beats/minute) Consider doses of diuretics ▲ angioedema with ACE inhibitor. Is the dose of loop diuretic achieving adequate relief of symptoms of fluid retention? Monitor carefully to achieve optimal dosing avoiding volume depletion from overdosing or fluid retention from underdosing. Increase the diuretic dose if congestive symptoms worsen and decrease when fluid retention is resolved. Contraindications to the use of digoxin If inadequate doses of diuretics are used when congestion is present, this may diminish the response to ACE inhibitors1. Excessive diuretic doses can increase the risk of hypotension and renal impairment with the ACE inhibitor. Reduce the dose of loop diuretic if necessary (eg low dose frusemide 20-40mg) to enable the use of maximum tolerated dose of ACE inhibitor7. Would compliance be improved by changed dosing times and frequency? Discuss options for timing of diuretic doses with the patient, eg taking the dose later in the day if more convenient or splitting the dose. Does the patient have contraindications to any medications? Contraindications to the use of ACE inhibitors ▲ bilateral renal artery stenosis, or a history of anuric renal failure during previous exposure to an ACE inhibitor ▲ advanced heart block. Contraindications to the use of angiotensin II receptor antagonists ▲ pregnancy ▲ intermittent complete heart block and second degree atrioventricular block ▲ Wolff-Parkinson-White syndrome ▲ ventricular tachycardia ▲ cor pulmonale ▲ constrictive pericarditis. Are adverse effects occurring? The major adverse effects of ACE inhibitors are hypotension, syncope, renal impairment, hyperkalaemia, angioedema (rare), rash and taste disturbance. Dry cough is not an absolute contraindication to the use of an ACE inhibitor but if troublesome, therapy may need to be discontinued. Exclude pulmonary congestion as the cause of the cough before withdrawing the ACE inhibitor1,3-4. Consider substitution of an angiotensin II receptor antagonist on a private prescription. Are there clinically important drug interactions? (see Table 2 below) Table 2 - Selected drug interactions (see Australian Medicines Handbook for further information and a full list) Drug Interacting drugs Interaction Management ACE inhibitors / angiotensin II receptor antagonists Loop or thiazide diuretics Increased risk of 1st dose hypotension Lithium Reduced excretion of lithium and increased risk of toxicity Potassium & potassium sparing diuretics Increased risk of hyperkalaemia NSAIDs / COX-2-selective NSAIDs May reduce effect of ACE inhibitor and precipitate peripheral or pulmonary oedema. Increased risk of acute renal impairment and hyperkalaemia Enhanced hypoglycaemic response Withhold diuretic for 24 hours before initiation of ACE inhibitor or angiotensin II receptor antagonist Monitor serum lithium levels when initiating, ceasing or changing the dose of an ACE inhibitor Use with caution, closely monitor serum potassium Avoid combined use. If concomitant use essential, monitor renal function, serum potassium and signs of heart failure Close monitoring of blood glucose Hypoglycaemic agents Loop and thiazide diuretics ACE inhibitors/ angiotensin II receptor antagonists Increased risk of 1st dose hypotension Digoxin Monitor serum potassium levels and supplement if necessary, ensure correction prior to initiating digoxin Increased serum lithium Monitor for signs of levels toxicity and serum lithium levels, adjust lithium dose if necessary Use combination with Reduced effectiveness of caution, monitor renal loop diuretics, increased function risk of nephrotoxicity Use with caution and Diuretic induced hypokalaemia may increase monitor serum potassium levels the risk of arrhythmia Lithium NSAIDs / COX-2-selective NSAIDs Drugs that prolong the QT interval (eg amiodarone, sotalol, terfenadine, astemizole, cisapride, anticholinergics) Digoxin Withhold diuretic for 24 hours before initiation of ACE inhibitor or angiotensin II receptor antagonist Diuretic induced hypokalaemia may increase the risk of digoxin induced arrhythmia Calcium, vitamin D and calcitriol (with thiazides) Increased risk of hypercalcaemia Monitor serum calcium Diuretics Corticosteroids Diuretic or corticosteroid induced hypokalaemia may increase the risk of digoxin induced arrhythmia Increased serum digoxin levels; additive negative effects on heart rate and conduction Increased serum digoxin levels, increased risk of toxicity Monitor serum potassium and correct hypokalaemia Diltiazem, verapamil Amiodarone, quinidine Antacids, sucralfate, bile acid binding resins Reduced absorption of digoxin Monitor serum digoxin levels and reduce dose if necessary Halve digoxin dose on initiation of amiodarone or quinidine, monitor serum digoxin levels and allow for long half-life of amiodarone Separate doses by at least 2 hours Is the drug effect and/or side effects monitored appropriately? Diuretic ▲ Monitor clinical status and electrolytes to avoid volume depletion and electrolyte disturbance7. Monitor potassium and magnesium, renal function, blood pressure and daily weight. potassium sparing diuretic or potassium supplement should be added2. Low doses of potassium sparing diuretic may be more effective than a potassium supplement1. In patients with renal impairment hypokalaemia rarely occurs. Digoxin ▲ Monitor serum digoxin levels, serum potassium and renal function to avoid toxicity2. ACE inhibitor ▲ Monitor blood pressure, renal function and electrolytes. A significant increase in serum creatinine occurs in up to 30% of patients with heart failure treated with an ACE inhibitor. ACE inhibitor and loop diuretic ▲ In patients with normal renal function, hypokalaemia occasionally occurs and a Action/Plan Changing therapy Increasing and maintaining the dose of an ACE inhibitor ▲ Ensure the patient is not volume depleted before increasing the dose. Increase the dose in small increments. Check blood pressure, renal function and electrolytes after each increase in dose4. Consider lowering the dose of diuretic at each increase in dose of ACE inhibitor. ▲ Maintain long term therapy even if symptoms do not improve. Adding a new therapy Commencing an ACE inhibitor ▲ The GP can initiate an ACE inhibitor and titrate therapy with careful monitoring in the first few weeks of therapy. (See Table 3 for “high risk” patients who should be referred for specialist care). ▲ Start at very low doses (see Table 1) to avoid hypotension and increase the dose gradually over 2-3 weeks3. Are there problems with compliance/concordance? Discuss with the patient how medications are taken and any problems with supply, administration or side effects. Ensure that the patient understands the goals of therapy and their current medication regimen including life long use of ACE inhibitor therapy. ▲ Withhold loop diuretics for at least 24 hours on initiation of ACE inhibitor7, in those taking high doses reduce the dose several days before commencing and correct any hypovolaemia. Withhold or reduce the dose of thiazide diuretics for at least 24 hours. Avoid potassium sparing diuretics (eg spironolactone) during initiation of therapy. ▲ If possible, start treatment in the evening, when supine, to minimise potential hypotensive effects. Otherwise, observation of the patient for a few hours after the first dose is advisable3. Use caution in the elderly to avoid falls. ▲ Monitor blood pressure, renal function and electrolytes prior to and approximately one week after initiating therapy and after each significant increase in dose4. When stable, monitor renal function and electrolytes at 6-12 month intervals3. ▲ If symptomatic hypotension, hyperkalaemia or a significant deterioration in renal function occurs (eg a serum creatinine rise of over 0.05mmol/L4), treatment should be modified. Renal function will often improve if the dose of concomitant diuretic therapy is reduced1. ▲ Symptomatic improvement may not be seen for weeks or months after initiation of an ACE inhibitor. ...continued on back page Table 3 - “High-risk” patients with any of the following should be referred for specialist care3 when commencing an ACE inhibitor ▲ cause of heart failure unknown ▲ serum sodium < 130mmol/L ▲ systolic blood pressure < 100mmHg ▲ moderate or severe heart failure ▲ serum creatinine > 0.13mmol/L (note - British ▲ valve disease. guidelines4 suggest creatinine >0.15mmol/L) 5 Action/Plan ...continued Commencing a diuretic Commencing spironolactone ▲ Monitor serum electrolytes, serum urate and ▲ In severe heart failure when symptoms continue (despite ACE inhibitor and loop diuretic therapy) in the patient with normal serum potassium and renal function, initiate spironolactone at 25mg each morning, increased to 50mg daily if tolerated. Monitor serum potassium closely. renal function 3-6 weeks after starting thiazide therapy. ▲ Loop diuretics carry a higher risk of electrolyte disturbances. Monitor serum electrolytes, renal function and urate one week after starting therapy and repeat periodically every 3-6 weeks. ▲ If serum potassium increases to >5.5mmol/L, ▲ If potassium supplementation is necessary, reduce dose of spironolactone to 25mg every second day. consider the use of spironolactone. If hypokalaemia is difficult to correct it may indicate low total body magnesium levels. References: 1. Advisory Council to Improve Outcomes Nationwide in Heart Failure. Consensus recommendations for the management of chronic heart failure. Am J Cardiol 1999;82(2A):1A-38A 2. Therapeutic Guidelines: Cardiovascular 3rd ed, Melbourne: June 1999. 3. Task Force of the Working Group on Heart Failure of the European Society of Cardiology. The treatment of heart failure. Eur Heart Journal 1997;18:736-753 4. Eccles M, Freemantle N, Mason J, for the North of England Guideline Develoment Group. North of England evidence based project: guideline for angiotensin converting enzyme inhibitors in primary care management of adults symptomatic heart failure. BMJ 1998;316:1369-1375 5. European Society of Cardiology Congress Symposium. Saving Lives in Heart Failure: Outcome Trials with ACE inhibitors, Vienna, Aug 1998. 6. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-17 7. Australian Medicines Handbook 2000. Adelaide 2000 8. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-533 The information contained in this material is derived from a critical analysis of a wide range of authoritative evidence. Any treatment decisions based on this information should be made in the context of the individual clinical circumstances of each patient. N P S National Prescribing Service Limited Our goal To improve health outcomes for Australians through prescribing that is : ▲ safe ▲ effective ▲ cost-effective Our programs To enable prescribers to make the best prescribing decisions for their patients, the NPS provides: ▲ information ▲ education ▲ support ▲ resources National Prescribing Service ACN 082 034 393 Level 1/31 Buckingham Street Surry Hills NSW 2010 Phone: 02 9699 4499 l Fax: 02 9699 5155 l email: info@nps.org.au l net: http://www.nps.org.au