Risk of Bleeding Complications with Antiplatelet Agents: Meta-Analysis of 338,191 Patients Enrolled in 50 Randomized Controlled Trials

Victor L. Serebruany, Alex I. Malinin, Roswith M. Eisert, David C. Sane

Research output: Contribution to journalArticle

Abstract

Antiplatelet therapy has been the focus of extensive clinical investigations over the last two decades. A variety of agents and regimens have been advanced for the prevention and treatment of vascular disease. Despite the proven life-saving clinical benefits of inhibiting platelets, this therapy is associated with an increased risk of bleeding. The objective of this study was to determine the risk of hemorrhage in the major classes of antiplatelet agents. Data from clinical trials published 1988-2002 in English were retrieved from MEDLINE, OVID, and CARDIOSOURCE. Only those studies in which patients had clinical follow-up for at least 1 month and in which a full description of hemorrhagic complications was reported were included. Information on sample size, study design, duration, agent, patient characteristics, and bleeding severity was independently and blindly reviewed. Data from 51 clinical trials with a total of 338,191 patients were analyzed. The antiplatelet agents were divided into 6 groups: aspirin (ASA) <100 mg; ASA ≥ 100 mg; dipyridamole, thienopyridines; intravenous and oral GP IIb/IIIa inhibitors. The variance estimate and confidence intervals were calculated for each treatment assignment. Low-dose aspirin and dipyridamole therapy were associated with the lowest risk of bleeding (3.6% and 6.7%, respectively). The highest rate of bleeding complications (44.6%) was associated with the GP IIa/IIIb inhibitors. Despite substantial differences in the reporting patterns of bleeding complications, low-dose ASA and dipyridamole therapy were associated with the lowest risk. Surprisingly, doses of ASA ≥ 100 mg caused a relatively high hemorrhagic event rate, which was comparable to that of ADP-receptor blockers. These findings should be considered when using combination antiplatelet and/or anticoagulant therapy with conventional doses of ASA.

Original languageEnglish (US)
Pages (from-to)40-47
Number of pages8
JournalAmerican Journal of Hematology
Volume75
Issue number1
DOIs
StatePublished - Jan 2004

Fingerprint

Platelet Aggregation Inhibitors
Meta-Analysis
Randomized Controlled Trials
Hemorrhage
Dipyridamole
Therapeutics
Aspirin
Purinergic P2Y Receptor Antagonists
Thienopyridines
Clinical Trials
Platelet Membrane Glycoprotein IIb
Proxy
Vascular Diseases
MEDLINE
Sample Size
Anticoagulants
Blood Platelets
Confidence Intervals

Keywords

  • Bleeding
  • Clinical trials
  • Complications
  • Meta analyses

ASJC Scopus subject areas

  • Hematology

Cite this

Risk of Bleeding Complications with Antiplatelet Agents : Meta-Analysis of 338,191 Patients Enrolled in 50 Randomized Controlled Trials. / Serebruany, Victor L.; Malinin, Alex I.; Eisert, Roswith M.; Sane, David C.

In: American Journal of Hematology, Vol. 75, No. 1, 01.2004, p. 40-47.

Research output: Contribution to journalArticle

Serebruany, Victor L. ; Malinin, Alex I. ; Eisert, Roswith M. ; Sane, David C. / Risk of Bleeding Complications with Antiplatelet Agents : Meta-Analysis of 338,191 Patients Enrolled in 50 Randomized Controlled Trials. In: American Journal of Hematology. 2004 ; Vol. 75, No. 1. pp. 40-47.
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