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

Abstract Background Nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin have been linked to heart failure, salt retention, adverse ventricular remodeling, and thrombosis. We therefore sought to assess their impact on cardiovascular events in outpatients with stable atherothrombotic disease. Methods We analyzed 44,095 patients in the REduction of Atherothrombosis for Continued Health (REACH) 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. End points 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 end points. Results Compared with NSAID nonusers (n = 39,675), NSAID users (n = 4420) 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 P  = .003) and for cardiovascular death/myocardial infarction/stroke (adj. HR 1.16; 95% CI, 1.03-1.30; P  = .02). There also was a higher risk of myocardial infarction (adj. HR 1.37; 95% CI, 1.12-1.68; P  = .002), stroke (adj. HR 1.21; 95% CI, 1.00-1.45; P  = .048), heart failure hospitalizations (adj. HR 1.18; 95% CI, 1.03-1.34; P  = .013), and ischemic hospitalizations (adj. HR 1.17; 95% CI, 1.07-1.27; P  = .001). Conclusion 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.