Background: Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.
Methods and Results: With the use of individual-level linkage of nationwide administrative registers, we identified a cohort of individuals without hospitalizations 5 years before first prescription claim of NSAIDs and without claimed drug prescriptions for selected concomitant medication 2 years previously.
The risk of cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke associated with the use of NSAIDs was estimated by case-crossover and Cox proportional hazard analyses.
The entire Danish population age 10 years or more consisted of 4,614,807 individuals on January 1, 1997, of which 2,663,706 (57.8%) claimed at least 1 prescription for NSAIDs during 1997 to 2005.
Of these; 1,028,437 individuals were included in the study after applying selection criteria regarding comorbidity and concomitant pharmacotherapy.
• Use of the nonselective NSAID diclofenac [sold under more than 30 trade names] and the selective cyclooxygenase-2 inhibitor rofecoxib [aka Vioxx, withdrawn from the market in 2004] was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42 [91% greater average risk of cardiovascular death with diclofenac]; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively) [66% greater average risk with Vioxx]…
…with a dose-dependent increase in risk. [Higher dose, more risk.]
• There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (odds ratio, 1.29; 95% confidence interval, 1.02 to 1.63) [29% average increase in risk of stroke],
• But naproxen (aka Aleve) was not associated with increased cardiovascular risk (odds ratio for cardiovascular death, 0.84; 95% confidence interval, 0.50 to 1.42) [16% lower average risk].
Conclusions: Individual NSAIDs have different degrees of cardiovascular safety, which must be considered when choosing appropriate treatment.
• Rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals,
• Whereas our results suggest that naproxen has a safer cardiovascular risk-profile. [But apparently also entails risk of GI bleeding/ulcers because it inhibits both COX-2 (inflammation promoting enzyme) and COX-1 (stomach lining protective enzyme).]
Source: Circulation: Cardiovascular Quality and Outcomes, Jun 8, 2010. PMID: 20530789, by Fosbol L, Jacobsen S, Rasmussen J, Sorensen R, Schramm T, Andersen S, Rasmussen S, Poulsen H, Kober L, Torp-Pedersen C, Gislason G. Department of Cardiology, Gentofte University Hospital, Hellerup; Departments of Rheumatology and Clinical Pharmacology, and The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen; National Institute of Public Health, Copenhagen, Denmark. [Email: ELF@heart.dk]