Review Finds Sildenafil Safe, Effective for PAH Treatment in Asian Adults

Pulmonary arterial hypertension (PAH) has a generally poor prognosis and no approved curative treatments. Sildenafil is one treatment option that has been shown to relieve PAH clinical symptoms, but the dose in study populations varies. A recent study published in Annals of Palliative Medicine aimed to provide clarity on the safety and effectiveness of 20-mg sildenafil taken 3 times a day in Asian patients with PAH.

PAH is characterized by a consistent increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR), potentially including permanent vascular remodeling. Without any treatment, PAH can have a devastating effect on patient quality of life. Targeted therapies in recent years have improved survival rates, but it remains a disease with no cure.

Sildenafil, a phosphodiesterase-5 inhibitor, has become the go-to drug for PAH treatment since its approval in 2005 and has shown efficacy in the short term. It works by reducing cyclic guanosine monophosphate degrading enzyme activity, which increases the antiproliferative and vasodilatory effects of endogenous nitric oxide to relax pulmonary arteries and improve blood flow. However, the current study authors note that the dose varies significantly in studies and previous research has not focused on Asian populations or other key outcomes.

Their analysis included data from 10 studies published between 2005 and 2010 and 480 patients. Data were pulled from electronic databases and included all randomized controlled trials and nonrandomized studies comparing 20 mg of sildenafil taken 3 times a day vs placebo or symptomatic treatment for Asian individuals with PAH.

Primary outcomes included performance in the 6-minute walk distance test (6MWD), dyspnea score on any scale, level of brain natriuretic peptide (BNP), change in World Health Organization functional class, mean PAP, systemic arterial oxygen saturation, and adverse events. Hemodynamic measures of right atrium pressure, PVR, and cardiac index; patient quality of life; time to clinical worsening; and incidence of clinical worsening and mortality were secondary outcomes.

Compared with placebo or symptomatic treatment, sildenafil showed significant improvements in 6MWD scores, mean PAP, arterial oxygen saturation, Borg scale dyspnea scores, BNP levels, and PVR.

Sildenafil patients saw a 57.68-meter improvement in 6MWD compared with symptomatic treatment and a mean PAP 4.13 mm Hg lower than patients given a placebo. Arterial oxygen saturation was also improved for patients on sildenafil, with a mean difference of 2.48%. The mean decrease in Borg dyspnea score was 0.99 points in patients receiving sildenafil compared with symptomatic treatment. BNP levels were a mean 86.16 pg/mL lower compared to placebo or symptomatic treatment.

Overall, the study authors consider the data conclusive, although the number of trials and sample size was small due to the research gap in sildenafil for Asian patients. Sildenafil was also generally well tolerated. Notable adverse effects, which were usually mild, included headache, flushing, dyspepsia, and diarrhea.

“Although data comparing sildenafil (20 mg/TID [3 times each day]) in adult Asian PAH patients is limited by the small number and sample size of included trials, our study provides conclusive evidence that sildenafil (20 mg/TID) is effective and safe,” the authors concluded, noting the improvements seen across primary outcomes in the analysis. “We suggest future trials should include a large sample, be of high methodological quality, and pay more attention to the long-term prognosis.”

Reference

Shi Q, Wang Z, Yang N, et al. Sildenafil for adult Asian patients with pulmonary arterial hypertension: a systematic review and meta-analysis. Ann Palliat Med. 2022;11(1):339-351. doi:10.21037/apm-21-3979