Comparative effectiveness of sildenafil for pulmonary hypertension due to left heart disease with HFrEF

There is no cure for pulmonary hypertension due to left heart disease (PH-LHD), but the rationale for using sildenafil to treat pulmonary arterial hypertension with heart failure with reduced ejection fraction (HFrEF) has been supported by short-term studies. We performed a meta-analysis to evaluate the effectiveness of sildenafil for PH-LHD with HFrEF. A systematic literature search of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials was conducted from inception through October 2014 for randomized trials and for observational studies with control groups, evaluating the effectiveness of sildenafil to treat PH-LHD with HFrEF. Sildenafil therapy decreased pulmonary arterial systolic pressure both at the acute phase and at the 6-month follow-up (weighted mean difference (WMD): -6.03 mm Hg, P=0.02; WMD: -11.47 mm Hg, P<0.00001, respectively). Sildenafil was found to reduce mean pulmonary artery pressure (WMD: -3 mm Hg, P=0.0004) and pulmonary vascular resistance (WMD: -60.0 dynes cm(-5), P=0.01) at the 3-month follow-up. Oxygen consumption at peak significantly increased to 3.66 ml min(-1) kg(-1) (P<0.00001), 3.36 ml min(-1) kg(-1) (P<0.00001) and 2.60 ml min(-1) kg(-1) (P=0.03) at 3, 6 and 12 months, respectively. There were significant reductions in ventilation to CO2 production slope of -2.00, -4.68 and -7.12 at 3, 6 and 12 months, respectively (P<0.00001). Sildenafil was superior to placebo regarding left ventricular ejection fraction at the 6-month follow-up (WMD: 4.35, P<0.00001), and it significantly improved quality of life. Sildenafil therapy could effectively improve pulmonary hemodynamics and cardiopulmonary exercise testing measurements of PH-LHD with HFrEF, regardless of acute or chronic treatment.