title: 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 < .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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiology, University of California, San Francisco.
authors.forename: Payal
authors.initials: P
authors.lastname: Kohli
authors.affiliation: Université Paris-Diderot, Sorbonne Paris-Cité, Hôpital Bichat, AP-HP and INSERM U-698, Paris, France.
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: TIMI Study Group, Boston, Mass; Brigham & Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.affiliation: University of North Carolina at Chapel Hill, NC.
authors.forename: Sidney C
authors.initials: SC
authors.lastname: Smith
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Eagle
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
authors.affiliation: University of Texas-Southwestern, Dallas.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Alberts
authors.affiliation: TIMI Study Group, Boston, Mass.
authors.forename: Elaine
authors.initials: E
authors.lastname: Hoffman
authors.affiliation: TIMI Study Group, Boston, Mass.
authors.forename: Jianping
authors.initials: J
authors.lastname: Guo
authors.affiliation: Assistance Publique-Hôpitaux de Paris, URCEST, Hôpital St Antoine, Paris; UPMC-Paris 06; and INSERM U-698, Paris, France.
authors.forename: Tabassome
authors.initials: T
authors.lastname: Simon
authors.affiliation: Université Paris-Diderot, Sorbonne Paris-Cité, Hôpital Bichat, AP-HP and INSERM U-698, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Sorbets
authors.affiliation: Tokai University, Kanagawa, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.affiliation: 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.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects*; D001161:Arteriosclerosis / Q000150:complications*; D050197:Atherosclerosis / Q000150:complications; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000401:mortality; D017202:Myocardial Ischemia / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality; D016017:Odds Ratio; D010045:Outpatients / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D013927:Thrombosis / Q000150:complications*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal
keywords: Heart failure; NSAID; Outcomes; Stable atherothrombosis