Effects of Spironolactone on Collagen Metabolism in Pulmonary Arterial Hypertension

Abstract

PURPOSE: Elevated aldosterone levels were previously documented in pulmonary arterial hypertension (PAH) subjects. We have also shown elevated aldosterone levels in our cohort of PAH patients. We undertook this study to determine the safety of spironolactone in PAH and secondly effects on circulating collagen biomarkers as an indirect measure of vascular remodeling. METHODS: After obtaining Baylor institutional review board approval and informed consent, PAH patients were prospectively enrolled at the Baylor PH center in a 16 week randomized clinical trial of crossover study design. Patients were randomized to receive 50 mg spironolactone or placebo. At the end of week 8, treatment arm for each subject were blindly switched. Inclusion criteria included age > 18 years, PAH diagnostic group I, ability to give informed consent, stable PAH meds for 1 month and stable background therapy for 2 weeks, normal renal and liver function. Baseline six‐minute walk distance (6MWD), WHO FC, BDS, BNP levels, LFTs, BMP and echocardiogram data was collected. Circulating levels of collagen biomarker levels were determined at week 0, 8 and 16. RESULTS: Thirty five patients completed this study. Mean age was 45±15 years and 87% were females. Fifteen had idiopathic PAH, 3 hereditary PAH, 12 were CTD‐PAH and 5 CHD‐PAH. Two patients were WHO FC I, 18 were WHO FC II and 12 were WHO FC III. Duration of illness was 5.0± 4.2 years. Baseline 6MWD was 439±114 meters, BDS was 2±2, BNP level was 69±18 pg/ml and aldosterone level was 6.6±5.6. One patient complaint of chest pain and jaw pain. None of the patients developed hyperkalemia (4.4±0.4 at baseline, 4.3±.4 at week 8 and 4.4±0.4 at week 16) or LFT abnormalities requiring discontinuation of study drug. None of the patients withdrew from the study due to study drug related sideeffects. CONCLUSIONS: Spironolactone is safe and well tolerated by PAH patients with no increased hyperkalemia or LFT abnormalities. CLINICAL IMPLICATIONS: Spironolactone is a safe medication to use in patient with PAH.