Use of New-Generation Oral Anticoagulant Agents in Patients Receiving Antiplatelet Therapy After an Acute Coronary Syndrome: Systematic Review and Meta-Analysis of Randomized Controlled Trials
What is the efficacy and safety of new-generation oral anticoagulant agents compared with placebo in patients receiving antiplatelet therapy after an acute coronary syndrome (ACS)?
Electronic databases were searched to identify prospective randomized placebo-controlled clinical trials that evaluated the effects of anti-Xa or direct thrombin inhibitors in patients receiving antiplatelet therapy after an ACS. Efficacy measures included stent thrombosis, overall mortality, and a composite endpoint of major ischemic events, while Thrombolysis in Myocardial Infarction (TIMI) defined major bleeding events were used as a safety endpoint. The net clinical benefit was calculated as the sum of composite ischemic events and major bleeding events.
For the period January 1, 2000, through December 31, 2011, the authors identified seven prospective randomized placebo-controlled clinical trials that met the study criteria, involving 31,286 patients. Based on the pooled results, the use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an ACS was associated with a dramatic increase in major bleeding events (odds ratio [OR], 3.03; 95% confidence interval [CI], 2.20-4.16; p < 0.001). Significant but moderate reductions in the risk for stent thrombosis or composite ischemic events were observed, without a significant effect on overall mortality. For the net clinical benefit, treatment with new-generation oral anticoagulant agents provided no advantage over placebo (OR, 0.98; 95% CI, 0.90-1.06; p = 0.57).
The authors concluded that the use of anti-Xa or direct thrombin inhibitors is associated with a dramatic increase in major bleeding events, which might offset all ischemic benefits in patients receiving antiplatelet therapy after an ACS.
The primary finding of this study is that the ischemic benefits achieved with the use of new-generation oral anticoagulant agents were offset by the higher risk for major bleeding events. The increased risk for bleeding may in fact explain the lack of significant benefit in overall mortality, despite the lower rate of ischemic events. Since the new-generation P2Y12 adenosine diphosphate (ADP) receptor antagonists may result in greater reductions of ischemic events, with substantially lower risk for bleeding complications, any potential role of oral anticoagulant agents after an ACS is debatable and needs further study.
Keywords: Acute Coronary Syndrome, Platelet Aggregation Inhibitors
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