Interesting Article : Combined Antiplatelet and Anticoagulant Drugs Raise Bleeding Risk

Summary and Comment

Combined Antiplatelet and Anticoagulant Drugs Raise Bleeding Risk

Use of dual or triple therapy requires caution.

Aspirin and clopidogrel are recommended for patients after acute myocardial infarction (AMI), and many AMI patients also have indications for a vitamin K antagonist. But combining these drugs can elevate risk for bleeding, which in turn can lead to morbidity and mortality.


To assess the safety of combinations of antiplatelet and anticoagulant drugs, Danish researchers used national registries to identify 40,000 adults who filled prescriptions within 90 days after first AMIs for one or more of three drugs: aspirin, clopidogrel, and a vitamin K antagonist.

During a mean follow-up of about 16 months, 1852 patients were hospitalized for nonfatal bleeding, and 115 fatal bleeding events occurred. With aspirin monotherapy as a reference, the adjusted relative risks for fatal and nonfatal bleeding were 1.23 for a vitamin K antagonist alone (the only nonsignificant difference), 1.33 for clopidogrel alone, 1.47 for aspirin plus clopidogrel, 1.84 for aspirin plus a vitamin K antagonist, 3.52 for clopidogrel plus a vitamin K antagonist, and 4.05 for all three (all significant differences). The adjusted number needed to harm for triple therapy was 12.5. Of patients who experienced nonfatal bleeding events, 38% had recurrent AMIs or died during follow-up compared with 18% of patients who didn't experience bleeding events.

Comment: This study was retrospective, but its size makes it credible. These findings strongly suggest that decisions to prescribe dual and triple combinations of antithrombotic medications should reflect careful, individualized risk-benefit evaluations that are based (whenever possible) on published evidence.

— Bruce Soloway, MD

Published in Journal Watch General Medicine January 12, 2010

Citation(s):

Sørensen R et al. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: A retrospective analysis of nationwide registry data. Lancet 2009 Dec 12; 374:1967.

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Dato' Dr. Ismail Yaacob
Medical Director/Consultant Physician
Kedah Medical Centre