Key result
Famotidine did not significantly improve 6-minute walk distance at 24 weeks compared to placebo (decrease of 17.0 m vs increase of 4.7 m; P=0.24) in patients with pulmonary arterial hypertension.
Why the study?
Right ventricular adaptation determines outcomes in PAH, but targeted right ventricular therapies are lacking, leaving it unknown whether H2-receptor antagonists improve outcomes.
Does famotidine 20 mg daily improve 6-minute walk distance in patients with pulmonary arterial hypertension?
RCT (n=80)
double-masked
1:1
No
Does famotidine 20 mg daily improve 6-minute walk distance in patients with pulmonary arterial hypertension?
Absolute Event Rate: -17% vs 4.7%
p-value: p=.24
Famotidine 20 mg daily does not improve functional capacity or secondary clinical outcomes in patients with pulmonary arterial hypertension.
Background Adaptation of the right ventricle is a key determinant of outcomes in pulmonary arterial hypertension (PAH). Despite a compelling rationale to develop targeted therapies for the right ventricle in PAH, no such treatments exist. H 2 -receptor antagonism is a potential myocardial-focused paradigm in heart failure. Research Question Do H 2 -receptor antagonists improve outcomes in patients with PAH? Study Design and Methods We conducted a 24-week, single-center, 1:1 randomized, double-masked, placebo-controlled trial of the H 2 -receptor antagonist famotidine in patients with a diagnosis of PAH. The primary outcome was change in 6-minute walk distance (6MWD) at 24 weeks. Secondary end points included B-type natriuretic peptide levels, New York Heart Association functional class, right ventricular parameters measured from echocardiography, health-related quality of life, and escalation in PAH-focused care. Results From May 2019 through July 2023, 80 participants were randomized with 79 receiving study drug. No significant difference in the primary outcome of 6MWD at 24 weeks was found, with an increase of 4.7 m seen in the placebo arm vs a decrease of 17.0 m in the famotidine arm ( P = .24). Also no differences were found in secondary end points at 24 weeks. Study drug was well tolerated, and safety profiles were similar between arms. Adherence and study conduct were good overall. Participants with methamphetamine-associated PAH were similar in all aspects to the study participants more broadly. Interpretation The results of this trial do not support the routine use of famotidine 20 mg daily as an adjunct therapy for the treatment of PAH. The findings of the Repurposing a Histamine Antagonist to Benefit Patients With Pulmonary Hypertension (REHAB-PH) trial argue against the practice of avoiding participants with methamphetamine-associated PAH in randomized clinical trials of novel therapies. Clinical Trial Registry ClinicalTrials.gov; No.: NCT03554291; URL: www.clinicaltrials.gov
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Leary et al. (2025) conducted an RCT in Pulmonary Arterial Hypertension (n=80). Famotidine vs. Placebo was evaluated on change in 6-minute walk distance (6MWD) at 24 weeks (p=.24). Famotidine did not significantly improve 6-minute walk distance at 24 weeks compared to placebo (decrease of 17.0 m vs increase of 4.7 m; P=0.24) in patients with pulmonary arterial hypertension.
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