title: Impact of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular outcomes in patients with stable atherothrombosis or multiple risk factors.
abstract: BACKGROUND
  We aimed to assess whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of cardiovascular (CV) events in stable patients with established atherothrombosis or multiple risk factors.
  
  
  METHODS
  We analysed the 23,728 European patients of the REACH Registry; 20,588 (86.8%) had established atherothrombotic disease and 3140 (13.2%) had multiple risk factors only. Aspirin (ASA) and/or NSAIDs use was determined at enrolment and ischemic events were recorded over two years of follow-up. cMACCE was defined as the composite of CV death, MI or stroke. Bleeding was defined as any bleeding leading to both hospitalisation and transfusion.
  
  
  RESULTS
  The mean age of population was 67.2±9.8years. At baseline, 1573 patients (6.6%) received NSAIDs and 15,395 (64.9%) received ASA. Four groups were defined: 1) no ASA/no NSAIDs, 2) ASA only, 3) NSAIDs only, 4) NSAIDs+ASA, with 7722 (32.5%), 14,433 (60.8%), 611 (2.6%) and 962 (4.1%) patients in these groups, respectively. Among the 22,028 (92.8%) with complete 2-year follow-up, 683 (3.2%) died from CV causes, while 395 (1.9%) had MI, 665 (3.1%) stroke, 1651 (7.6%) cMACCE and 199 (1.0%) bleeding. After adjustment, NSAID use was independently associated with an increased risk of stroke (OR 1.635; 95% CI 1.239-2.159, p<0.001), and a trend towards an increased bleeding rate (OR 1.554; CI 95% 0.960-2.51, p=0.07). No association was found between NSAID use and MI or MACCE.
  
  
  CONCLUSIONS
  In stable atherothrombosis patients, the use of NSAIDs appears to be independently associated with an increased cerebrovascular event risk.
authors: Institut de Cardiologie (APHP), INSERM CMR937 and Univ Paris 6, Pitié-Salpêtrière Hospital, Paris, France.
authors: Olivier
authors: O
authors: Barthélémy
authors: Institut für Herzinfarktforschung Ludwigshafen, an der Universität Heidelberg, Ludwigshafen, Germany.
authors: Tobias
authors: T
authors: Limbourg
authors: Institut de Cardiologie (APHP), INSERM CMR937 and Univ Paris 6, Pitié-Salpêtrière Hospital, Paris, France.
authors: Jean Philippe
authors: JP
authors: Collet
authors: Institut de Cardiologie (APHP), INSERM CMR937 and Univ Paris 6, Pitié-Salpêtrière Hospital, Paris, France.
authors: Farzin
authors: F
authors: Beygui
authors: Institut de Cardiologie (APHP), INSERM CMR937 and Univ Paris 6, Pitié-Salpêtrière Hospital, Paris, France.
authors: Johanne
authors: J
authors: Silvain
authors: Institut de Cardiologie (APHP), INSERM CMR937 and Univ Paris 6, Pitié-Salpêtrière Hospital, Paris, France.
authors: Anne
authors: A
authors: Bellemain-Appaix
authors: Institut de Cardiologie (APHP), INSERM CMR937 and Univ Paris 6, Pitié-Salpêtrière Hospital, Paris, France.
authors: Guillaume
authors: G
authors: Cayla
authors: Institut de Cardiologie (APHP), INSERM CMR937 and Univ Paris 6, Pitié-Salpêtrière Hospital, Paris, France.
authors: Thomas
authors: T
authors: Chastre
authors: Swiss Cardiovascular Centre, Division of Clinical and Interventional Angiology, Inselspital, University Hospital, 3010 Bern, Switzerland.
authors: Iris
authors: I
authors: Baumgartner
authors: Department of Neurology, Asklepios Klinik Altona, Hamburg Medical School, Hamburg, Germany.
authors: Joachim
authors: J
authors: Röther
authors: Institut für Herzinfarktforschung Ludwigshafen, an der Universität Heidelberg, Ludwigshafen, Germany.
authors: Uwe
authors: U
authors: Zeymer
authors: VA Boston Healthcare System, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
authors: Deepak L
authors: DL
authors: Bhatt
authors: INSERM U-698, Université Paris 7 and AP-HP, Paris, France.
authors: Gabriel
authors: G
authors: Steg
authors: Institut de Cardiologie (APHP), INSERM CMR937 and Univ Paris 6, Pitié-Salpêtrière Hospital, Paris, France. Electronic address: gilles.montalescot@psl.aphp.fr.
authors: Gilles
authors: G
authors: Montalescot
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal