Background: Statins confer cardiovascular benefits beyond the reduction of serum cholesterol through antiproliferative and antiinflammatory mechanisms and induction of endothelial nitric oxide expression. In pneumonectomized rats injected with monocrotaline, simvastatin reversed established pulmonary hypertension and conferred a 100% survival advantage.
Study objectives: To evaluate the safety and efficacy of simvastatin for treatment of patients with pulmonary arterial hypertension (PAH).
Design: Open-label observational study performed at Stanford University Medical Center. Sixteen patients with primary and secondary causes of PAH, World Health Organization (WHO) classes I (n = 2), II (n = 4), III (n = 3), IV (n = 7), are described. Simvastatin was prescribed at 20 to 80 mg/d and continued in the absence of adverse effects.
Measurements and results: Serial measurements of 6-min walk (6MW) performance, hemodynamics, and echocardiographic estimates of right ventricular systolic pressures (RVSPs) were recorded on each patient. Simvastatin treatment was not associated with hepatic dysfunction, muscle necrosis, or other adverse events. Individual patients demonstrated improvements in 6MW performance, improvements in cardiac output, or decreases in RVSP that may be attributable to simvastatin treatment. Overall, the rate of disease progression appeared to be attenuated, and WHO class IV patients demonstrated improved survival.
Conclusions: Simvastatin treatment appears safe in patients with PAH.