Abstract 3478: Risk of Bleeding Associated with Combination versus Single Antiplatelet Agents in 142,916 Patients Enrolled in 22 Randomized Controlled Trials
Background: A variety of antiplatelet agents and regimens as a mono-, or combination therapy have been introduced for the prevention and treatment of vascular disease. Despite the proven life-saving outcome benefits of mild platelet inhibition, the associated risk of bleeding with more aggressive strategies is unclear. The objective of this study was to compare the risk of hemorrhagic complications associated with a single agent or reference regimen versus combination or advanced antiplatelet therapy.
Methods: Data from clinical trials published 1988–2006 in English were retrieved from MEDLINE, OVID, and CARDIOSOURCE. Only those studies in which patients had clinical follow-up for at least one 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. Minor, major, intracranial, and fatal bleeding rates were assessed. The relative risk and confidence intervals were calculated for each trial and each type of bleeding.
Results: Combination antiplatelet therapy is associated with a significantly increased risk of major (RR 1.54, p < 0.0001) and minor bleeding events (RR 1.62, p < 0.0001), while the differences in the fatal bleeding (RR 1.10 p=0.46) and hemorrhagic strokes (RR 1.06, p= 0.61) were similar with combination or monotherapy.
Conclusion: Patients treated with combination antiplatelet agents are at higher almost doubled risk to develop minor or major, but not fatal bleeding or hemorrhagic stroke. These findings should be considered with caution, especially when choosing an antiplatelet strategy for the long-term treatment or prevention of vascular disease.