Long-term use of antirheumatic drugs may help to reduce the risk of heart attacks and strokes in these patients, according to a new analysis of data from the international QUEST-RA observational study.

A team from Europe, Argentina and the US, led by Antonio Naranjo from the University of Las Palmas de Gran Canaria in Spain, looked at the prevalence of cardiovascular disease in patients with rheumatoid arthritis (RA), the association of RA with traditional cardiovascular risk factors, the clinical features of RA and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational, cross-sectional cohort of outpatients with rheumatoid arthritis who were receiving regular clinical care.

Data on 4,363 participants in the QUEST-RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) study were collected from 48 sites in 15 countries between January 2005 and October 2006.

The cohort represented what the researchers, reporting on the study in the open-access journal Arthritis Research & Therapy, described as “a typical RA population”: 78% of patients were female, more than 90% were Caucasian, the mean age was 57 years and the mean disease duration was 11 years. The study involved a clinical assessment by a rheumatologist and a self-report questionnaire completed by the patients.

As Naranjo et al note, RA is associated with increased mortality, predominantly due to acceleration of coronary artery and cerebrovascular atherosclerosis, a phenomenon seen in both established and early rheumatoid arthritis. Cardiovascular events occur around 10 years earlier in RA patients than the general population, suggesting that rheumatoid arthritis, like diabetes mellitus, is an independent risk factor for premature ischaemic heart disease.

At the same time, other studies have suggested that treating RA with DMARDs such as methotrexate or TNF-alpha blockers, may reduce this risk. Methotrexate, for example, has been associated with a significantly lower risk of cardiovascular events in RA patients compared with patients who have never taken a DMARD.

Strong correlation
The researchers found that the prevalence of lifetime cardiovascular events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke and 9.3% for any cardiovascular event. The prevalence of cardiovascular risk factors was 32% for hypertension, 14% for hyperlipidaemia, 8% for diabetes, 43% for smoking (ever), 73% for physical inactivity and 18% for obesity.

Adjusted for age, sex, nationality and disease activity, as well as traditional risk factors such as lack of exercise, smoking, diabetes and high cholesterol levels, there was a strong correlation between prolonged exposure to methotrexate, with a hazard ratio (HR, i.e., relative risk) of 0.85 (95% confidence interval (CI) 0.81-0.89), leflunomide (HR 0.59; 95% CI 0.43 -0.79), sulfasalazine (HR 0.92; 95% CI: 0.87-0.98), glucocorticoids (HR 0.95; 95% CI 0.92-0.98) or biological agents (HR 0.42; CI 0.21-0.81; p<0.05) and a reduced risk of cardiovascular morbidity.

For example, taking methotrexate – the most widely used DMARD – for just one year was associated with an 18% reduction in the risk of heart attack and an 11% decrease in the risk of stroke.

“Our study provides further support for the influence of both traditional and RA-specific risk factors in the development of cardiovascular events, especially heart attacks,” the researchers wrote. “As assessed by this study, the risk was lower with the prolonged use of methotrexate, sulfasalazine, glucocorticoids, leflunomide and TNF-alpha blockers.”

The possibility that antirheumatic therapy may lower the risk of cardiovascular complications “is tantalising”, commented Dr Ronald van Vollenhoven of Sweden’s Karolinska Institute in an accompanying editorial. “The current study, while not exactly proving this point, adds a further measure of support to the concept, and suggests that it must now be formally addressed.”