Simvastatin as a treatment for pulmonary hypertension trial

Am J Respir Crit Care Med. 2010 May 15;181(10):1106-13. doi: 10.1164/rccm.2009111-699oc.


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 +/- 11 g in the statin group (P = 0.045) and increased 3.9 +/- 14 g in the placebo group. The treatment effect was -9.1 g (P = 0.028). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels decreased significantly in the statin group (-75 +/- 167 fmol/ml; P = 0.02) but not the placebo group (49 +/- 224 fmol/ml; P = 0.43; overall treatment effect -124 fmol/ml; P = 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.

Trial registration: NCT00180713.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension, Pulmonary / blood
  • Hypertension, Pulmonary / diagnostic imaging
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / pathology
  • Hypertrophy, Right Ventricular / blood
  • Hypertrophy, Right Ventricular / diagnostic imaging
  • Hypertrophy, Right Ventricular / drug therapy
  • Hypertrophy, Right Ventricular / pathology
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Simvastatin / therapeutic use*
  • Ultrasonography
  • Young Adult


  • Antihypertensive Agents
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Simvastatin

Associated data