Non-steroidal anti-inflammatory drugs and myocardial infarctions: comparative systematic review of evidence from observational studies and randomised controlled trials.
OBJECTIVE
The comparative risk of myocardial infarction (MI) with cyclo-oxygenase-2-specific drugs and traditional non-steroidal anti-inflammatory drugs (NSAIDs) was determined.


METHODS
The results of studies of a suitable size in colonic adenoma and arthritis-that had been published in English and from which crude data about MIs could be extracted-were evaluated. Medline, Embase and Cinahl (2000-2006) databases, as well as published bibliographies, were used as data sources. Systematic reviews examined MI risks in case-control and cohort studies, as well as in randomised controlled trials (RCTs).


RESULTS
14 case-control studies (74 673 MI patients, 368 968 controls) showed no significant association of NSAIDs with MI in a random-effects model (OR 1.17; 95% CI 0.99 to 1.37) and a small risk of MI in a fixed-effects model (OR 1.32; 95% CI 1.29 to 1.35). Sensitivity analyses showed higher risks of MI in large European studies involving matched controls. Six cohort studies (387 983 patient years, 1 120 812 control years) showed no significant risk of MI with NSAIDs (RR 1.03; 95% CI 1.00 to 1.07); the risk was higher with rofecoxib (RR 1.25; 95% CI 1.17 to 1.34) but not with any other NSAIDs. Four RCTs of NSAIDs in colonic adenoma (6000 patients) showed an increased risk of MI (RR 2.68; 95% CI 1.43 to 5.01). Fourteen RCTs in arthritis (45 425 patients) showed more MIs with cyclo-oxygenase-2-specific drugs (Peto OR 1.6; 95% CI 1.1 to 2.4), but fewer serious upper gastrointestinal events (Peto OR 0.40; 95% CI 0.31 to 0.53).


CONCLUSIONS
The overall risk of MI with NSAIDs and cyclo-oxygenase-2-specific drugs was small; rofecoxib showed the highest risk. There was an increased MI risk with cyclo-oxygenase-2-specific drugs compared with NSAIDs, but less serious upper gastrointestinal toxicity.
Scott
P A
PA
Department of Cardiology, Queen Alexandra Hospital, Portsmouth, UK.
Kingsley
G H
GH
Smith
C M
CM
Choy
E H
EH
Scott
D L
DL
D000236:Adenoma / Q000188:drug therapy; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001168:Arthritis / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D009203:Myocardial Infarction / Q000139:chemically induced*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018570:Risk Assessment
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors