SIMVASTATIN IN PAH

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Currently available therapies for pulmonary arterial hypertension (PAH) are of limited efficacy and associated with multiple adverse effects. The statin drugs have recently been shown to possess a broad range of actions on vascular wall function, independent of cholesterol lowering, which would be expected to have a beneficial impact on the vascular remodeling of PAH. Animal studies have documented impressive attenuation and regression of experimental pulmonary hypertension by simvastatin. The objective of this research is to test the efficacy and safety of simvastatin in patients with PAH. This is a 12 week, double-blind, placebo-controlled trial of simvastatin 40 mg/day in patients with either primary pulmonary hypertension or PAH associated with connective tissue disease who are clinically stable and already receiving conventional FDA approved therapy with bosentan, epoprostenol or treprostinil. The primary outcome measure is exercise tolerance as assessed by the change in 6 minute walk distance from baseline to 12 weeks. A total of 4 visits per subject are required: screen, baseline, 6 and 12 weeks. A total of 70 subjects will be enrolled (35 patients per group) in collaboration with Stanford University. Additional efficacy parameters will include Borg dyspnea score, NYHA functional class and time to clinical worsening. Safety of research participants will be monitored closely through collection of adverse events throughout the course of the study and laboratory testing, which will be conducted at screening, baseline and 2, 6 and 12 weeks. Particular attention will be paid to three potential concerns: myositis, liver function abnormalities and pregnancy occurrence.