Myocardial infarction and individual nonsteroidal anti‐inflammatory drugs meta‐analysis of observational studies

Abstract

ObjectiveTo conduct a systematic review of observational studies on the risk of acute myocardial infarction (AMI) with use of individual nonsteroidal anti-inflammatory drugs (NSAIDs).MethodsA search of Medline (PubMed) for observational studies published from 1990 to 2011 identified 3829 articles; 31 reported relative risk (RR) of AMI with use of individual NSAIDs versus nonuse of NSAIDs. Information abstracted in a standardized form from 25 publications was used for the meta-analysis on 18 independent study populations.ResultsRandom-effects RR (95% confidence interval (CI)) was lowest for naproxen 1.06 (0.94–1.20), followed by celecoxib 1.12 (1.00–1.24), ibuprofen 1.14 (0.98–1.31), meloxicam 1.25 (1.04–1.49), rofecoxib 1.34 (1.22–1.48), diclofenac 1.38 (1.26–1.52), indometacin 1.40 (1.21–1.62), etodolac 1.55 (1.16–2.06), and etoricoxib 1.97 (1.35–2.89). Heterogeneity between studies was present. For new users, RRs (95% CIs) were for naproxen, 0.85 (0.73–1.00); ibuprofen, 1.20 (0.97–1.48); celecoxib, 1.23 (1.00–1.52); diclofenac, 1.41 (1.08–1.86); and rofecoxib, 1.43 (1.21–1.66).Except for naproxen, higher risk was generally associated with higher doses, as defined in each study, overall and in patients with prior coronary heart disease. Low and high doses of diclofenac and rofecoxib were associated with high risk of AMI, with dose–response relationship for rofecoxib. In patients with prior coronary heart disease, except for naproxen, duration of use ≤3 months was associated with an increased risk of AMI.ConclusionsMost frequently NSAIDs used in clinical practice, except naproxen, are associated with an increased risk of AMI at high doses or in persons with diagnosed coronary heart disease. For diclofenac and rofecoxib, the risk was increased at low and high doses. Copyright © 2013 John Wiley & Sons, Ltd.

Hypolipidemic effects of nimesulide and celecoxib in experimentally induced hypercholesterolemia in rabbits

“…The available clinical data on COX-2 inhibitors pertaining to cardiovascular endpoints have been summarized (32). These data suggest the risk of cardiovascular events associated with the use of NSAIDs, except for naproxen.…”

“…These data suggest the risk of cardiovascular events associated with the use of NSAIDs, except for naproxen. High doses of NSAIDs are associated with increased risk of acute myocardial infarction (32) and, although short-term treatment with the COX-2 specific inhibitor rofecoxib does not impair endotheliumdependent or -independent vascular function in healthy volunteers (33), in patients with coronary artery disease, cardiovascular adverse effects are observed both at low and high doses (32). Although nimesulide and celecoxib are relatively safer drugs at the doses used in this study, we are cautious in generalizing our findings to other COX-2 inhibitors.…”

Hjerte, smerte – kardiovaskulær sikkerhet og ikke-steroide antiinflammatoriske midler

“…De fleste som har undersøkt mulige sammenhenger mellom dose ikke-steroid antiinflammatorisk middel og økt risiko for kardiovaskulaere hendelser, har påvist en dose-effektsammenheng (7,13,17,18,31). Unntaket er naproksen, hvor risikoøkningen har vaert fravaerende (tab 2), og en metaanalyse (6) der man ikke kunne påvise at den vaskulaere risikoen til verken selektive COX-2-hemmere eller tradisjonelle ikke-steroide antiinflammatoriske midler var doseavhengig.…”

“…I motsetning til dette viste Solomon og medarbeidere (17) i sin metaanalyse med celekoksib at også den relative risikoen var høyere hos individer med en allerede etablert risiko for hjerte-og karsykdommer. Andre som har undersøkt dette, har også kommet frem til at den relative risikoøkningen er større hos pasienter med en i utgangspunktet forhøyet risiko for kardiovaskulaere hendelser (18,31).…”

Clinical guidelines «Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice». Part II

“…Критерием оценки стала частота фатального и нефатального инфаркта мио-карда, развитие которого было зафиксировано почти у 100 000 пациентов. Для напроксена, как и ожидалось, был по-казан наименьший риск -отношение шансов (ОШ) -1,06 (0,94-1,2) [155] (рис. 3).…”