February 24th, 2015
Increased Risk with NSAIDs Following Myocardial Infarction
The cardiovascular safety of nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and diclofenac has been the subject of considerable uncertainty and controversy. Now a new study published in JAMA raises specific concerns about the safety of these drugs in the highly vulnerable population of people who have had a recent myocardial infarction.
Using data from several linked national registries, Danish researchers studied over 60,000 people with a first MI, a third of whom received a prescription for an NSAID following discharge. Overall, people who took NSAIDs had double the rate of bleeding events as people not taking the drugs. In particular, people taking standard dual antiplatelet therapy with aspirin and clopidogrel had 3.3 bleeding events per 100 person-years; the addition of an NSAID increased this risk to 7.6 events per 100 person-years. The rate of cardiovascular events (including CV death, recurrent MI, ischemic stroke, or systemic arterial emboli) was also increased by the addition of an NSAID to other drugs.
A significant increase in risk was found for both the selective COX-2 inhibitors rofecoxib and celecoxib and nonselective COX inhibitors like ibuprofen and diclofenac. Further, an increased bleeding risk was found even when NSAIDs were used for just 3 days or fewer.
The authors note that although European and US guidelines and regulatory agencies discourage the use of NSAIDs in people with established heart disease, the use of these drugs in this population remains common and the drugs are often available over-the-counter.
In an accompanying editorial, Charles Campbell and David Moliterno write that the study adds to the available evidence that “while NSAIDs can be helpful and at times necessary medications for satisfactory quality of life, use of these medications among patients with a history of a recent MI is likely to be associated with clinically meaningful bleeding and ischemic risks.” Until PRECISION, a randomized controlled trial testing NSAIDS in people with or at high risk for CV disease is completed, “practitioners would do well to advise patients with cardiovascular disease against all NSAID use (except low-dose aspirin), especially patients with a recent acute coronary syndrome.”
Commenting on the study, Peter Berger said that although “registry analyses like these are associated with confounding that is usually impossible to overcome with any methods of adjustment,” unless there are better data from clinical trials, “the use of NSAIDs should be discouraged unless absolutely necessary.” Sanjay Kaul agreed, noting that this “observational study falls within the range of uncertain reliability,” but that until better evidence becomes available “clinicians should exercise caution in prescribing these drugs” after a recent cardiovascular event.