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Correspondence
to further validate the data presented in the study by Wang et al,1
there is a lot of promise if we can achieve a clinically relevant
therapeutic effect with a major decrease in side effects.
To Bleed or Not To Bleed…
To the Editor:
Wang et al (February 2010)1 reported that thrombolytic therapy
for pulmonary thromboembolism with one-half the dose of recombinant tissue-type plasminogen activator (rt-PA) was associated
with similar clinical improvement as the full dose, but complications of bleeding were greatly reduced. This is a landmark study
that addresses one of the main issues that limit the use of this
therapy: concerns about bleeding complications. Ibrahim et al2
had already shown, in a 15,000-patient cohort, that in patients with
pulmonary thromboembolism receiving thrombolytics bleeding
complications occur in approximately 5.3% of patients.
Decreasing the frequency of that feared complication is a major
step in the use of this therapeutic approach. To illustrate this better,
we organized the data obtained from Wang et al in a 2 3 2 format
(Table 1), from which we can calculate the attributable risk percentage (AR%), which is the percentage of bleeding complications
that could be prevented among patients receiving a regular dose of
rt-PA if they received a low dose rt-PA, with the following formula:
AR% 5 ([Incidence of bleedingFull dose of rt-PA 2 Incidence of
bleedingLow dose of rt-PA]Incidence of bleedingFull dose of rt-PA) 3
100 5 ([32 100 2 17100][32 100]) 3 100 5 46.8 5 47%.
Furthermore, if we want to have a better idea of what this potential change in practice may do to the group of patients to which
it is targeted, then we should look at the population attributable
risk percentage (PAR%), calculated with the following formula:
PAR% 5 ([Incidence of bleedingTotal population – Incidence of
bleedingLow dose rt-PA]Incidence of bleedingTotal population) 3
100 5 ([23.7100 – 17100]23.7100) 3 100 5 28.2%.
This represents the percentage of bleeding complications in the
patient population with pulmonary thromboembolism who are
given thrombolytics that is due to receiving the regular dose of
rt-PA and could be eliminated by using a lower dose of rt-PA.
Certainly, the treatment of pulmonary thromboembolism with
the use of thrombolytics in hemodynamically unstable patients
has the potential to save lives.3 We look forward to using thrombolytics in a safer manner, and even though more studies are needed
Table 1—Major Bleeding Complications
in Patients From the Study by Wang et al1
Bleeding
No Bleeding
Incidence,
Complication Complication Total per 100 per year
Normal-dose
rt-PA
Low-dose
rt-PA
17
36
53
32
11
54
65
17
rt-PA 5 recombinant tissue-type plasminogen activator.
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Downloaded From: http://journal.publications.chestnet.org/ on 02/11/2015
Tahuanty A. Pena, MD
Detroit, MI
Affiliations: From the Division of Pulmonary, Critical Care and
Sleep Medicine, Wayne State UniversityDetroit Medical Center.
Financial/nonfinancial disclosures: The author has reported
to CHEST that no potential conflicts of interest exist with any
companies/organizations whose products or services may be discussed in this article.
Correspondence to: Tahuanty A. Pena, MD, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University
Detroit Medical Center, 3990 John R., 3 Hudson, Detroit, MI 48201;
e-mail: tpena@med.wayne.edu
© 2010 American College of Chest Physicians. Reproduction
of this article is prohibited without written permission from the
American College of Chest Physicians (http://www.chestpubs.org/
site/misc/reprints.xhtml).
DOI: 10.1378/chest.10-1291
References
1. Wang C, Zhai Z, Yang Y, et al; for the China Venous Thromboembolism (VTE) Study Group. Efficacy and safety of low
dose recombinant tissue-type plasminogen activator for the
treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest. 2010;137(2):
254-262.
2. Ibrahim SA, Stone RA, Obrosky DS, Geng M, Fine MJ, Aujesky D.
Thrombolytic therapy and mortality in patients with acute pulmonary embolism. Arch Intern Med. 2008;168(20):2183-2192.
3. Hirsh J, Guyatt G, Albers GW, Harrington R, Schünemann HJ;
American College of Chest Physician. Antithrombotic and
thrombolytic therapy: American College of Chest Physicians
evidence-based clinical practice guidelines (8th edition). Chest.
2008;133(6 Suppl):110S-112S.
Response
To the Editor:
We appreciate Dr Pena’s comments on our article in CHEST
(February 2010).1 Indeed, bleeding complication is one of the
main concerns that limit the use of thrombolytic therapy for pulmonary thromboembolism (PTE).2 We appreciate Dr Pena’s calculations using attributable risk percentage (AR%) (the percentage
of bleeding complications that could be prevented among patients
receiving a regular dose of recombinant tissue-type plasminogen
activator [rt-PA] if they received a low dose rt-PA) and population attributable risk percentage (the percentage of bleeding complications in the population with PTE given thrombolytics that is
due to receiving the regular dose of rt-PA and could be eliminated
by using a lower dose of rt-PA, as described in Dr Pena’s letter),
which provide a better and clearer illustration for the benefit of
Correspondence