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.
RCT Entities:
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.
Authors: Toshihiko Nishimura; John L Faul; Gerald J Berry; Laszlo T Vaszar; Daoming Qiu; Ronald G Pearl; Peter N Kao Journal: Am J Respir Crit Care Med Date: 2002-08-15 Impact factor: 21.405
Authors: Martin R Wilkins; Gideon A Paul; Julian W Strange; Nina Tunariu; Wendy Gin-Sing; Winston A Banya; Mark A Westwood; Alexander Stefanidis; Leong L Ng; Dudley J Pennell; Raad H Mohiaddin; Petros Nihoyannopoulos; J Simon R Gibbs Journal: Am J Respir Crit Care Med Date: 2005-03-04 Impact factor: 21.405
Authors: Toshihiko Nishimura; Laszlo T Vaszar; John L Faul; Guohua Zhao; Gerald J Berry; Lingfang Shi; Daoming Qiu; Gail Benson; Ronald G Pearl; Peter N Kao Journal: Circulation Date: 2003-09-08 Impact factor: 29.690
Authors: Reda E Girgis; Dechun Li; Xinhua Zhan; Joe G N Garcia; Rubin M Tuder; Paul M Hassoun; Roger A Johns Journal: Am J Physiol Heart Circ Physiol Date: 2003-05-15 Impact factor: 4.733
Authors: Mariëlle C van de Veerdonk; Sophie A Dusoswa; J Tim Marcus; Harm-Jan Bogaard; Onno Spruijt; Taco Kind; Nico Westerhof; Anton Vonk-Noordegraaf Journal: Int J Cardiovasc Imaging Date: 2013-12-04 Impact factor: 2.357
Authors: David J Ross; Greg Hough; Susan Hama; Jamil Aboulhosn; John A Belperio; Rajan Saggar; Brian J Van Lenten; Abbas Ardehali; Mansoureh Eghbali; Srinivasa Reddy; Alan M Fogelman; Mohamad Navab Journal: Pulm Circ Date: 2015-12 Impact factor: 3.017