Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective and extensively used pain-killers, particularly in the treatment of chronic musculoskeletal problems.  However, doubts about their safety in patients with coronary disease have surfaced, particularly since the NSAID-like COX1 inhibitor, rofecoxib, was withdrawn from the market after a demonstrated  increase in cardiovascular events.  Despite these concerns, compelling data on the effects of other NSAIDs are still sparse and their safety when used chronically is largely unknown.

Performing a post-hoc analysis on data gathered  from the INternational VErapamil Trandolapril STudy (INVEST), which enrolled over 22,000 patients with hypertension and coronary artery disease, Bavry et al. collated data on NSAID use and outcomes. The primary composite outcome was all-cause death, nonfatal myocardial infarction, or nonfatal stroke assessed using a multivariate model to control for confounders.  In all, 882 patients were assessed to be chronic users with the remaining 21,694 defined as nonchronic NSAID users (n = 14,408 for never users and n=7,286 for intermittent users).  After a mean follow-up of 2.7 years, the primary outcome occurred at a rate of 4.4 events per 100 patient-years in the chronic NSAID group, versus 3.7 in the nonchronic NSAID group (HR 1.47; 95% CI, 1.19-1.82; P=0.0003). This was driven by a significant increase in cardiovascular mortality (HR 2.26; 95% CI, 1.70-3.01; P<.0001) with an increase in all cause mortality also seen.  Although an increase in blood pressure by NSAIDs has been previously hypothesised to increase the risk of cardiovascular events, no such difference was seen in this cohort with the chronic use group actually having a slightly lower mean pressure over the 2.7 year period of follow-up. Unfortunately, no data were available on the usage of individual NSAID drugs and so comparisons between class-members were not possible.

Conclusions

In this large retrospective study, chronic NSAID use was associated with significant increases in both cardiovascular and all cause mortality.  A careful assessment of the absolute risk-benefit profile should be made before using these drugs in patients at risk of cardiovascular disease.

• Bavry AA, Khaliq A, Gong Y, Handberg EM, Cooper-Dehoff RM and Pepine CJ. Harmful Effects of NSAIDs among Patients with Hypertension and Coronary Artery Disease. Am J Med. 2011 Jul;124(7):614-20.