Sildenafil for Asian Adult Patients with Pulmonary Arterial Hypertension: A Systematic Review and Meta-analysis

Abstract

Background: The prognosis of patients with untreated pulmonary arterial hypertension (PAH) has historically been poor. Previous studies have recommended that sildenafil was beneficial, but the dose varies greatly. We aimed to evaluate sildenafil effectiveness and safety in dose of 20mg/three times a day (TID) for Asian adult patients with PAH. Methods: Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane Library, CBM, CNKI and Wanfang Data) from their inception to May 2020 were searched. We included all randomized controlled trials and non-randomized studies of interventions that comparing sildenafil (20mg/TID) versus placebo or symptomatic treatment for PAH Asian adults. Results: Eight studies totaling 364 participants were included. When compared to symptomatic treatment, sildenafil treated patients were more likely to walk 68.3 meters further in six-minute walk distance [mean difference (MD)=68.3 meters, 95% confidence interval (CI) 48.85 to 87.76, P＜0.00001], to achieve an improvement in systemic arterial oxygen saturation (MD=2.48%, 95% CI 1.26 to 3.71, P＜0.00001) and in score on the Borg scale of dyspnea (MD=-0.99 points, 95% CI -1.45 to -0.53, P＜0.00001). The total number of patients with WHO class III and IV also showed downtrend. When compared to placebo, sildenafil was associated with a greater reduction in the mean pulmonary artery pressure (MD=-4.13 mmHg, 95% CI -6.52 to -1.74, P=0.0007) and level of brain natriuretic peptide (MD=-86.16 pg /mL, 95% CI -103.39 to -68.93, P＜0.00001). The most adverse reactions were headache, flushing, dyspepsia, and diarrhea, which were relatively mild. Conclusions: Sildenafil in dose of 20mg/TID is well tolerated in Asian adults with PAH, and associated with statistically significant improvements in exercise capacity, cardio-pulmonary function and haemodynamic indices. The long-term prognosis still needs to be evaluated and confirmed by further trials.Systematic review registration: PROSPERO CRD42020190582