Concomitant NSAIDs with antithrombotic therapy after MI worsen outcomes

In a study of patients assigned antithrombotic therapy after MI, concomitant use of nonsteroidal anti-inflammatory drugs were associated with increased risk for bleeding and excess thrombotic events, regardless of treatment duration.

Researchers analyzed patients aged at least 30 years identified through nationwide administrative registries in Denmark who were admitted with first-time MI and survived for 30 days after discharge between 2002 and 2011 (n = 61,971; mean age, 67.7 years; 63% men).

Patients were categorized according to whether they claimed prescriptions for aspirin, clopidogrel and a vitamin K antagonist, alone or in combination, as well as whether they claimed prescriptions for any NSAIDs. During the study period, 34% of patients filled at least one NSAID prescription.

The primary outcomes were bleeding requiring hospitalization and a composite CV outcome (CV-related death, nonfatal recurrent MI and stroke). Median follow-up was 3.5 years.

Anne-Marie Schjerning Olsen, MD, PhD, from the department of cardiology at Copenhagen University Hospital Gentofte in Hellerup, Denmark, and colleagues found that 29.2% of patients died, 8.5% experienced bleeding events and 30% experienced CV events during the study period.

More events in NSAID group

Crude incidence rates for bleeding were 4.2 events per 100 person-years (95% CI, 3.8-4.6) for those who received NSAID treatment and 2.2 events per 100 person-years (95% CI, 2.1-2.3) for those who did not. Crude incidence rates for CV events were 11.2 per 100 person-years (95% CI, 10.5-11.9) among those with NSAID treatment and 8.3 per 100 person-years (95% CI, 8.2-8.4) among those without NSAID treatment, according to the researchers.

In a multivariate analysis, Schjerning Olsen and colleagues determined that those who had received NSAID treatment were at elevated risk for bleeding (HR = 2.02; 95% CI, 1.81-2.26) and CV events (HR = 1.4; 95% CI, 1.3-1.49) compared with those who had not.

The results were consistent regardless of type of antithrombotic treatment, type of NSAID or duration of NSAID use. Even 0 to 3 days of treatment was associated with higher bleeding risk compared with no treatment, according to the researchers. “There was no safe therapeutic window for concomitant NSAID use,” they wrote.

“[The bleeding finding] is of considerable public health relevance because NSAIDs are among the most commonly used medications worldwide and any antithrombotic treatment invariably increases bleeding risk,” Schjerning Olsen and colleagues wrote. “The biological explanation of the [CV] risk with NSAIDs is still unresolved but is likely to involve inhibition of COX-2 mediated prostacyclin vasodilation as well as pharmacodynamics interactions associated with individual drugs, including ibuprofen. … More research is needed to confirm these findings; however, physicians should exercise appropriate caution when prescribing NSAIDs for patients who have recently experienced MI.”

Consistent with prior research

In a related editorial, Charles L. Campbell, MD, and Cardiology Today's Intervention Editorial Board member David J. Moliterno, MD, wrote that the findings “are consistent with prior reports and further support current guidelines that warn against the use of NSAIDs among patients with ischemic [CVD]. It is concerning to note that roughly one-third of patients in the cohort were prescribed concomitant NSAIDs despite their recent MI.”

Until the results of the PRECISION trial, which randomly assigned approximately 24,000 patients with symptomatic rheumatoid arthritis or osteoarthritis who have or are at high risk for CVD to one of three NSAIDs, are available, “practitioners would do well to advise patients with [CVD] against all NSAID use (except low-dose aspirin), especially patients with a recent [ACS],” wrote Campbell, from the division of cardiovascular medicine at University of Tennessee–Chattanooga, and Moliterno, from the Gill Heart Institute and division of cardiovascular medicine at the University of Kentucky, Lexington. – by Erik Swain

Disclosure: One researcher reports receiving grants from Bristol-Myers Squibb, Cardiome, Daiichi Sankyo, Merck and Sanofi and personal fees from Cardiome, Daiichi Sankyo, Merck and Sanofi. Campbell and Moliterno report no relevant financial disclosures.

Source: www.healio.com