DMARD treatment reduces risk of acute MI in RA patients, but current biologic use carries increased risk

Disease-modifying antirheumatic drugs (DMARDs) reduce the risk of acute myocardial infarction (MI) in patients with rheumatoid arthritis (RA), according to results of an observational study published in the journal Arthritis & Rheumatism.

The finding "suggests that the benefits of DMARDs in RA may extend beyond their arthritis-remitting effects," the authors said. The researchers also found no increased risk of acute MI with the use of cyclooxygenase (COX-2) inhibitors in the same population.

The incidence of cardiovascular disease (CVD), and the mortality rate associated with it, is higher in patients with RA than in the general population, and CVD is the most common cause of death in patients with RA, according to the authors. Some scientists have hypothesized that treatments designed to control the chronic inflammation associated with RA also may affect the rate of cardiovascular events.

The study cohort of 107,908 subjects came from the PharMetrics Patient-Centric Outcomes Database, which contains standardized claims information involving physician visits, hospitalizations, and prescription dispensing for >55 million patients from 75 health insurance plans. The authors studied data from January 1, 1999, to December 31, 2003, choosing the start date because drugs such as leflunomide, biologic agents, and COX-2 inhibitors became broadly available afterward.

The cohort included patients in whom RA had been diagnosed and who were dispensed a prescription for anti-RA medication and had at least 1 year of information available before cohort entry, defined as the date of the first anti-RA prescription. Subjects had to be free of acute MI, including previous MI, during the 1-year period, and had to be aged at least 18 years at cohort entry. Prescribed medications included glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, and DMARDs including methotrexate, hydroxychloroquine, chloroquine, leflunomide, biologic agents (infliximab, etanercept, anakinra), sulfasalazine, gold compounds, minocycline, penicillamine, and immunosuppressants.

Subjects were aged an average of 54 years at cohort entry. Seventy-four percent were women. They were followed until their health plan enrollment ended, they died, the study period ended, or they were hospitalized with acute MI for the first time. Ten controls-matched on sex, age, and time of study entry-were selected for each case of acute MI identified during follow-up. The index date used for each case-control set was the date of acute MI occurrence in the case. The researchers then reviewed all medications used by the subjects in the year prior to the index date. The acute MI cases and their matched cohorts were aged 65 years at the index date, 55% were women, and acute MI was experienced, on average, 14 months after cohort entry.

After adjusting for acute MI risk factors, the authors used conditional logistic regression to estimate the rate ratio of acute MI associated with current use of anti-RA therapy.

Five hundred fifty-eight acute MI cases occurred during follow-up (3.4 per 1,000 per year). The authors found that current use of any DMARD significantly reduced the rate of acute MI (adjusted RR=0.80; 95% CI, 0.65–0.98). This effect was observed with all DMARDs, including methotrexate (RR=0.81; 95% CI, 0.60–1.08), leflunomide (RR=0.28; 95% CI, 0.12–0.65), and other traditional DMARDs (RR=0.67; 95% CI, 0.46–0.97). Patients currently using biologic agents demonstrated a 30% greater risk of acute MI (RR=1.30; 95% CI, 0.92–1.83). The use of glucocorticoids was associated with an increased rate of acute MI (RR=1.32; 95% CI, 1.02–1.72), but an increase in the rate of acute MI was not associated with the use of nonselective NSAIDs (RR=1.05; 95% CI, 0.81–1.36) or COX-2 inhibitors (RR=1.11; 95% CI, 0.87–1.43).

Although they said they were surprised that the use of COX-2 inhibitors celecoxib and rofecoxib did not increase the risk of acute MI, the authors noted the varying results of earlier studies involving COX-2 inhibitors.

According to the researchers, DMARDs may decrease cardiovascular risk in patients with RA through their steroid-sparing effect, through their ability to reduce systemic inflammation, or indirectly by improving physical activity. Study limitations included that the exclusive use of the PharMetrics database prohibited researchers from confirming RA diagnosis, validating acute MI outcome, and verifying patient use of prescribed medication. The authors said that more data would be needed to determine the cardiovascular effects of newer DMARDs.

SOURCE Suissa S, Bernatsky S, Hudson M. Antirheumatic drug use and the risk of acute myocardial infarction. Arthritis Rheum. 2006;55:531–536.