NSAID Use and Association With Cardiovascular Outcomes in Outpatients With Stable Atherothrombotic Disease

Study Questions:

What is the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on cardiovascular events in outpatients with stable atherothrombotic disease?


The investigators analyzed 44,095 patients in the REACH (REduction of Atherothrombosis for Continued Health) registry with information on NSAID use and 4-year follow-up. Cox proportional hazard models, including NSAID use as a time-dependent covariate, were constructed and adjusted for key baseline characteristics. Endpoints of interest included multivariate adjusted: cardiovascular death/myocardial infarction/stroke/ischemic hospitalizations; cardiovascular death/myocardial infarction/stroke; hospitalization for heart failure; and individual components of the composite endpoints.


Compared with NSAID nonusers (n = 39,675), NSAID users (n = 4,420) were older (70 vs. 68 years), more frequently female and white, and had more baseline heart failure and atherosclerotic risk factors (hypertension, dyslipidemia, diabetes, reduced creatinine clearance) (all p < 0.001). NSAID use was associated with an increased hazard for cardiovascular death/myocardial infarction/stroke/ischemic hospitalizations (adjusted hazard ratio [adj. HR], 1.12; 95% confidence interval [CI], 1.04-1.21; p = 0.003) and for cardiovascular death/myocardial infarction/stroke (adj. HR, 1.16; 95% CI, 1.03-1.30; p = 0.02). There also was a higher risk of myocardial infarction (adj. HR, 1.37; 95% CI, 1.12-1.68; p = 0.002), stroke (adj. HR, 1.21; 95% CI, 1.00-1.45; p = 0.048), heart failure hospitalizations (adj. HR, 1.18; 95% CI, 1.03-1.34; p = 0.013), and ischemic hospitalizations (adj. HR, 1.17; 95% CI, 1.07-1.27; p = 0.001).


The authors concluded that among patients with stable atherothrombosis, NSAID use is associated with a higher risk of myocardial infarction, stroke, and hospitalizations for both ischemia and heart failure.


This study reports that NSAID use in a population of patients with stable atherothrombotic disease or risk factors for vascular disease is associated with an increase in adjusted rates of multiple 4-year major adverse cardiovascular outcomes, including the endpoints of cardiovascular death, myocardial infarction, stroke, ischemic hospitalizations, and hospitalization for heart failure. However, no significant difference in bleeding requiring hospitalization and transfusion was associated with NSAID use. These data provide further evidence for the careful evaluation of the risk:benefit ratio of NSAID use in patients with stable atherothrombotic disease.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension

Keywords: Odds Ratio, Stroke, Myocardial Infarction, Follow-Up Studies, Creatinine, Registries, Dyslipidemias, Proportional Hazards Models, Outpatients, Heart Failure, Cardiovascular Diseases, Confidence Intervals, Risk Assessment, Hypertension, Diabetes Mellitus

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