Spironolactone in pulmonary arterial hypertension: results of a cross‐over study

Abstract

The renin–angiotensin–aldosterone system is implicated in the pathophysiology of pulmonary arterial hypertension. We undertook this study to determine the effects of spironolactone, a mineralocorticoid receptor blocker, on collagen metabolism in pulmonary arterial hypertension patients. After obtaining institutional review board approval and informed consent, 42 pulmonary arterial hypertension patients were prospectively enrolled and 35 patients completed the 16-week randomized double-blinded crossover clinical trial. Subjects received 50 mg spironolactone or placebo and at the end of week 8, treatment arm was switched. Circulating levels of collagen biomarkers, brain natriuretic peptide, and aldosterone levels were measured, and six-minute walk distance, liver function tests, and echocardiogram data were collected at weeks 0, 8, and 16. Mean age was 45 ± 15 years and 87% were females. At baseline, brain natriuretic peptide and aldosterone levels were 74 ± 95 pg/ml and 7 ± 8 pg/ml, respectively. There was no change in the levels of amino-terminal propeptide of procollagen type III (PIIINP), MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio at weeks 8 and 16 compared to baseline values in placebo arm and treatment arm. The baseline six-min walk distance was 436 ± 115 meters at baseline and no change in walk distance was noted at weeks 8 and 16 ( P = 0.372). None of the patients developed hyperkalemia or liver function test abnormalities at weeks 8 and 16 requiring discontinuation of study drug. Our study showed no change in collagen metabolite levels in pulmonary arterial hypertension patients treated with spironolactone. Spironolactone was safe and well tolerated by pulmonary arterial hypertension patients with no increased hyperkalemia or liver function test abnormalities.

Inhibition of HDAC1 alleviates monocrotaline-induced pulmonary arterial remodeling through up-regulation of miR-34a

“…During this time, the expression of TIMP-1 and TIMP-2 are also up-regulated to inhibit excessive MMP activity through a balancing mechanism [ 39 ]. However, since the balancing effect is limited, the ratio of MMP-9/TIMP-1 and MMP-2/TIMP-2 is elevated, which contributes to excessive ECM accumulation and the development of PAH [ 43 ].…”

COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection

“…The mineralocorticoid receptor (MR) blocker spironolactone has antifibrotic properties and has shown to be beneficial in patients with systolic left heart failure. Spironolactone is frequently used as a diuretic in PAH [ 42 ].…”

Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension

“…No change in walk distance was noted at weeks 8 and 16. 299 A post-hoc study from ARIES 1 and ARIES 2 clinical trials indicated some positive effects in the addition of spironolatone to ambrisantan. 300 Subsequently, a prospective study examined in 30 subjects with PAH, the effect of spironolactone when added to ambrisentan on exercise capacity (NCT02253394).…”