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.


One Response to “Increased Risk with NSAIDs Following Myocardial Infarction”

  1. Nothing new here.

    STEMI Guidelines(January 2013):

    Epidemiological studies and retrospective analyses of RCTs have suggested that nonsteroidal anti-inflammatory drugs and selective cyclooxygenase II enzyme (COX-2) inhibitors may be associated with an increased risk of death, reinfarction, cardiac rupture, hypertension, renal insufficiency, and HF (448,449,450,451). Nonsteroidal anti-inflammatory drugs and COX-2 inhibitors are contraindicated in patients with STEMI. They should not be initiated in the acute phase and should be discontinued in patients using them before hospitalization.

    NSTEMI/ACS guidelines(December 2014):

    Selective COX-2 inhibitors and other nonselective NSAIDs have been associated with increased cardiovascular risk, and the risk appears to be amplified in patients with established cardiovascular disease (17,234,235,467,469). In a large Danish observational study of patients with first MI (n=58,432), the HR and 95% CI for death were 2.80 (2.41 to 3.25) for rofecoxib, 2.57 (2.15 to 3.08) for celecoxib, 1.50 (1.36 to 1.67) for ibuprofen, 2.40 (2.09 to 2.80) for diclofenac, and 1.29 (1.16 to 1.43) for other NSAIDs (234). There were dose-related increases in risk of death and non–dose-dependent trends for rehospitalization for MI for all drugs (234,467). An AHA scientific statement on the use of NSAIDs concluded that the risk of cardiovascular events is proportional to COX-2 selectivity and the underlying risk in the patient (237). Nonpharmacological approaches were recommended as the first line of treatment, followed by the stepped-care approach to pharmacological therapy, as shown in Figure 4.

    The latter guidelines does endorse naproxen(IIa) or slective COX-2if other therapies fail.