Patients with rheumatoid arthritis (RA) who did not have preexisting coronary artery disease (CAD) and used methotrexate (MTX) for at least 24 months or a tumor necrosis factor (TNF) antagonist for at least 40 months were significantly less likely to develop cardiovascular disease (CVD) than those who did not use MTX or anti TNF therapy, according to researchers from Geisinger Medical Center in Danville, Pennsylvania, USA.

Lead researcher Rasa Bozaite-Gluosniene and her colleagues worked with electronic health records for 1718 adult RA patients with at least 2 outpatient encounters and no prevalent CVD for their analysis to assess the impact of medication exposure over time. The primary outcome was CVD defined as CAD, any cardiac revascularization procedure, stroke or transient ischemic attack (TIA), peripheral artery disease (PAD), abdominal aortic aneurysm (AAA), or cardiac revascularization procedures.

Median follow-up was 3.4 years, and the median age was 57 years. One-third of participants had used an anti TNF-α (n=588); 62% (n=1119) had used MTX.

The researchers identified 127 cases of incident CVD, confirmed by chart review: 48 cases of CAD, primarily myocardial infarction, unstable angina, or revascularization; 45 strokes or TIAs; and 34 cases of PAD or AAA.

Among patients who were taking MTX, the case rate for CAD per 1000 patient-years was 14.6 (10.6 to 20.1) versus 23.2 (18.8 to 28.5) in nonusers, translating into a 37% risk reduction (incidence rate ratio=0.63; 0.42 to 0.93). The median exposure to MTX was 22 months, with the risk of CVD falling as the duration of MTX use increased. Patients with 23 months or more of exposure experienced a 72% reduction in risk (p<0.001).

The incidence rate for CAD per 1000 person-years was 37.5 for nonusers versus 17.6 for users of MTX. The hazard for incident CAD in MTX users was 0.54 (95% CI, 0.37 to 0.77; p=0.001) compared with nonusers. For patients who were taking MTX for more than 24 months, the hazard for incident CAD was 0.33 (95% CI, 0.22 to 0.50; p<0.001). The incident rate for CAD per 1000 person-years was 32.1 in TNF-α inhibitor users versus 11.8 for nonusers. Among the TNF-α inhibitor users, the hazard for incident CAD was 0.54 (95% CI, 0.30 to 0.95; p=0.03) compared with nonusers. In patients who were taking TNF-α inhibitors for more than 24 months, the hazard was 0.24 (95% CI, 0.12 to 0.51; p<0.001). Patients who took the drugs for more than 35 months had a 93% reduced risk of CAD (0.01 to 0.52; p=0.010). Median TNF-α exposure was 17 months.

Study limitations included the observational design and limited information on smoking status, family history of CVD, level of physical activity, and use of aspirin. The study presenters concluded that the use of MTX or TNF-α inhibitors can provide some protection against CVD in patients with RA.