NSAID Use After Myocardial Infarction | Journal Scan

Study Questions:

What is the risk of bleeding and cardiovascular events among patients with prior myocardial infarction (MI) taking antithrombotic drugs and for whom nonsteroidal anti-inflammatory drug (NSAID) therapy was then prescribed?


The investigators used nationwide administrative registries in Denmark (2002-2011), and studied patients 30 years or older admitted with first-time MI and alive 30 days after discharge. Subsequent treatment with aspirin, clopidogrel, or oral anticoagulants and their combinations, as well as ongoing concomitant NSAID use, was determined. The exposure of interest was the use of NSAIDs with ongoing antithrombotic treatment after first-time MI. The main outcome measures were the risk of bleeding (requiring hospitalization) or a composite cardiovascular outcome (cardiovascular death, nonfatal recurrent MI, and stroke) according to ongoing NSAID and antithrombotic therapy, calculated using adjusted time-dependent Cox regression models.


The study included 61,971 patients (mean age, 67.7 [standard deviation, 13.6] years; 63% men); of these, 34% filled at least one NSAID prescription. The number of deaths during a median follow-up of 3.5 years was 18,105 (29.2%). A total of 5,288 bleeding events (8.5%) and 18,568 cardiovascular events (30.0%) occurred. The crude incidence rates of bleeding (events per 100 person-years) were 4.2 (95% confidence interval [CI], 3.8-4.6) with concomitant NSAID treatment and 2.2 (95% CI, 2.1-2.3) without NSAID treatment, whereas the rates of cardiovascular events were 11.2 (95% CI, 10.5-11.9) and 8.3 (95% CI, 8.2-8.4). The multivariate-adjusted Cox regression analysis found increased risk of bleeding with NSAID treatment compared with no NSAID treatment (hazard ratio, 2.02 [95% CI, 1.81-2.26]), and the cardiovascular risk was also increased (hazard ratio, 1.40 [95% CI, 1.30-1.49]). An increased risk of bleeding and cardiovascular events was evident with concomitant use of NSAIDs, regardless of antithrombotic treatment, types of NSAIDs, or duration of use.


The authors concluded that among patients receiving antithrombotic therapy after MI, the use of NSAIDs was associated with increased risk of bleeding and excess thrombotic events, even after short-term treatment.


In this observational study, concomitant use of NSAIDs was associated with increased risk of bleeding and excess thrombotic events, even after short-term treatment in patients who had experienced an MI. While the antiplatelet properties of NSAIDs would be expected to increase bleeding risk when used concomitantly with antithrombotics, possible mechanisms that may explain excess thrombotic risk include inhibition of COX-2–mediated prostacyclin vasodilatation as well as pharmacodynamic interactions with aspirin at the level of platelet COX-1. Based on this study and other available data, it would appear prudent to be careful when prescribing NSAIDs for patients who have recently experienced an MI.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Anticoagulation Management and ACS

Keywords: Anti-Inflammatory Agents, Non-Steroidal, Anticoagulants, Aspirin, Blood Platelets, Cardiovascular Diseases, Fibrinolytic Agents, Myocardial Infarction, Risk Factors, Stroke, Acute Coronary Syndrome, Registries, Regression Analysis

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