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GI Bleeding with Antithrombotic Drug Combinations

Combinations of antithrombotic and anti-inflammatory drugs further increase the risk for GI bleeding associated with single-drug therapies.

To what extent do combinations of two antithrombotic drugs, or one antithrombotic drug and one anti-inflammatory drug, increase the risk for gastrointestinal bleeding? To answer this question, researchers conducted a population-based case-control study of more than 4000 patients with a first-ever episode of GI bleeding and about 40,000 age-matched controls identified from the U.K. General Practice Research Database. All analyses were adjusted for numerous potential clinical and demographic confounders.

Monotherapies with warfarin, clopidogrel, aspirin, or a nonsteroidal anti-inflammatory drug were each associated with a significantly increased risk for GI bleeding (roughly 1.5- to 2-fold). Combinations of two drugs were associated with much higher risk. For example, the risk (compared with exposure to none of these drugs) was roughly sixfold for warfarin plus aspirin, fivefold for warfarin plus an NSAID, fourfold for clopidogrel plus aspirin, and threefold for clopidogrel plus an NSAID. Risks for patients receiving cyclooxygenase (COX-2) inhibitors were similar to those for patients receiving nonselective NSAIDs (whether these drugs were used alone or in combinations).

Comment: The specific risks for GI bleeding calculated in this study should be considered as only approximate, given that confidence intervals were wide. Nevertheless, the results drive home the point that combinations of anticoagulants, antiplatelet drugs, and anti-inflammatory drugs heighten substantially the already increased risks for GI bleeding associated with single-drug therapies. Combinations of these drugs should be prescribed only according to evidence-based indications.

— Allan S. Brett, MD

Published in Journal Watch General Medicine September 4, 2007

Citation(s):

Delaney JA et al. Drug–drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ 2007 Aug 14; 177:347-51.

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