Level 2: Mid-level evidence

Use of both traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors has previously been linked to an increased risk of stroke and other vascular events. For patients with cardiovascular disease, current guidelines recommend NSAIDs for pain relief only in patients for whom there are no alternatives and only at the lowest doses and durations necessary (Circulation. 2007;115:1634-1642).

Now, a nationwide cohort study in Denmark suggests that any NSAID use may increase the risk of death or recurrent MI in patients with a previous MI (Circulation. 2011;123:2226-2235). Prescription NSAID use was assessed through records from a national registry of 83,677 patients (mean age 68 years) who were hospitalized with a first MI from 1997 to 2006.

During the study period, 42.3% of patients received an NSAID prescription, most commonly ibuprofen (23%) or diclofenac (13.4%), and 35,257 patients either died or had another MI. In analyses stratified by treatment duration, the risk of death or recurrent MI during NSAID treatment was significantly increased at all time points from less than one week of treatment to more than three months. Hazard ratios ranged from 1.45 (95% CI: 1.29-1.62) to 1.68 (95% CI: 1.5-1.88). Individual drugs were associated with increased risk at most time points in subgroup analyses. Risk was increased at all time points for diclofenac, and was highest for less than one week of use (HR=3.26; 95% CI: 2.75-3.86).

Alan Ehrlich, MD, is an assistant clinical professor in family medicine at the University of Massachusetts Medical School in Worcester.