Blood pressure changes during methotrexate treatment: results from a randomized placebo-controlled trial among patients with cardiovascular risk

OBJECTIVE: Low-dose MTX (LD-MTX) has been associated with a reduced risk of cardiovascular disease (CVD) among patients with systemic rheumatic diseases but not among the general population. Prior reports suggest that LD-MTX may reduce blood pressure (BP). We studied the effect of LD-MTX on BP. METHOD: We examined data that compared LD-MTX to placebo in a randomized double-blind controlled clinical trial conducted among patients who had known CVD but without rheumatic disease. Systolic and diastolic BP (SBP, DBP) were collected as vital sign measurements at each scheduled study visit during 5 years of follow-up. Longitudinal SBP and DBP were compared between patients of LD-MTX and placebo arms using a linear mixed model. RESULT: Data were used from 2391 patients randomized to LD-MTX and 2395 to placebo, with a mean follow-up of 26 months. At baseline, SBP and DBP were normally distributed with similar medians [SBP: 128 mmHg (IQR 118-139), DBP: 74 mmHg (IQR 67-80)] between patients from both treatment groups; 93% patients reported at baseline using at least one type of medication for hypertension. After treatment, compared with placebo, the estimated differences in changes of SBP and DBP in the LD-MTX group were <1 mm (SBP: β = -0.75 mmHg, 95% CI -0.02 to -1.49; DBP: β = -0.56 mmHg, 95% CI -0.12 to -1.01). CONCLUSION: Patients randomized to LD-MTX without systemic rheumatic disease had no clinically meaningful difference in BP compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01594333.