NSAID use and association with cardiovascular outcomes in outpatients with stable atherothrombotic disease

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.

Kohli P(1), Steg PG(2), Cannon CP(3), Smith SC Jr(4), Eagle KA(5), Ohman EM(6), Alberts MJ(7), Hoffman E(8), Guo J(8), Simon T(9), Sorbets E(2), Goto S(10), Bhatt DL(11); REACH Registry Investigators.

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 < .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 = .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.

Author information:

(1) Division of Cardiology, University of California, San Francisco.

(2) Université Paris-Diderot, Sorbonne Paris-Cité, Hôpital Bichat, AP-HP and INSERM U-698, Paris, France.

(3)TIMI Study Group, Boston, Mass; Brigham & Women’s Hospital, Harvard Medical School, Boston, Mass.

(4) University of North Carolina at Chapel Hill, NC.

(5) University of Michigan, Ann Arbor.

(6) Duke Clinical Research Institute, Durham, NC.

(7) University of Texas-Southwestern, Dallas.

(8) TIMI Study Group, Boston, Mass.

(9) Assistance Publique-Hôpitaux de Paris, URCEST, Hôpital St Antoine, Paris; UPMC-Paris 06; and INSERM U-698, Paris, France.

(10) Tokai University, Kanagawa, Japan.

(11) TIMI Study Group, Boston, Mass; Brigham & Women’s Hospital, Harvard Medical School, Boston, Mass; VA Boston Healthcare System, Boston, Mass. Electronic address: dlbhattmd@post.harvard.edu.

PMID: 24280110 [PubMed – indexed for MEDLINE]

. Am J Med. 2014 Jan;127(1):53-60.e1. doi: 10.1016/j.amjmed.2013.08.017. Epub 2013 Nov 23.