Simvastatin as a Treatment for Pulmonary Hypertension Trial

Rationale: In animal models of pulmonary hypertension, simvastatin has been shown to reduce pulmonary artery pressure and induce regression of associated right ventricular (RV) hypertrophy.Objectives: To assess the therapeutic value of simvastatin in patients with pulmonary arterial hypertension (PAH).Methods: Forty-two patients with PAH were randomized to receive either simvastatin (80 mg/d) or placebo in addition to current care for 6 months, and thereafter offered open-label simvastatin.The primary outcome was change in RV mass, assessed by cardiac magnetic resonance (CMR).Measurements and Main Results: At 6 months, RV mass decreased by 5.2 6 11 g in the statin group (P 5 0.045) and increased 3.9 6 14 g in the placebo group.The treatment effect was 29.1 g (P 5 0.028).N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels decreased significantly in the statin group (275 6 167 fmol/ml; P 5 0.02) but not the placebo group (49 6 224 fmol/ml; P 5 0.43; overall treatment effect 2124 fmol/ml; P 5 0.041).There were no significant changes in other outcome measures (including 6-minute walk test, cardiac index, and circulating cytokines).From 6 to 12 months, both RV mass and NT-proBNP increased toward baseline values in 16 patients on active treatment who continued with simvastatin but remained stable in 18 patients who switched from placebo to simvastatin.Two patients required a reduction in dose but not cessation of simvastatin.Conclusions: Simvastatin added to conventional therapy produces a small and transient early reduction in RV mass and NT-proBNP levels in patients with PAH, but this is not sustained over 12 months.Clinical trial registered with www.clinicaltrials.gov(NCT00180713).