Simvastatin as a treatment for pulmonary hypertension trial.
BACKGROUND
In animal models of pulmonary hypertension, simvastatin has been shown to reduce pulmonary artery pressure and induce regression of associated right ventricular (RV) hypertrophy.


OBJECTIVE
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).


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.
Wilkins
Martin R
MR
Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, United Kingdom. m.wilkins@imperial.ac.uk
Ali
Omar
O
Bradlow
William
W
Wharton
John
J
Taegtmeyer
Anne
A
Rhodes
Christopher J
CJ
Ghofrani
Hossein A
HA
Howard
Luke
L
Nihoyannopoulos
Petros
P
Mohiaddin
Raad H
RH
Gibbs
J Simon R
JS
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D019821:Simvastatin / Q000627:therapeutic use*; D014463:Ultrasonography; D055815:Young Adult
D000959:Antihypertensive Agents; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D019821:Simvastatin
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