Efficacy and Safety of Vardenafil in the Treatment of Pulmonary Arterial Hypertension (EVALUATION) Study Group. Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study

Rationale: Although the phosphodiesterase type 5 inhibitors sildenafil and tadalafil have demonstrated efficacy in patients with pulmonary arterial hypertension (PAH), monotherapy with these agents has not been conclusively shown to reduce clinical worsening events. Objectives: To evaluate the safety and efficacy of the phosphodiesterase type 5 inhibitor vardenafil in Chinese patients with PAH. Methods: In a randomized, double-blind, placebo-controlled study, 66 patients with PAH were randomized 2:1 to vardenafil (5 mg once daily for 4wk then 5mg twice daily; n=44) or placebo (n=22) for 12 weeks. Patients completing this phase were then treated with openlabel vardenafil (5 mg twice daily) for a further 12 weeks. Measurements and Main Results: At Week 12, the mean placebocorrected 6-minute walking distance was increased with vardenafil (69 m; P<0.001), and this improvement was maintained for at least 24 weeks. Vardenafil also increased the mean placebo-corrected cardiac index (0.39 L·min-1·m-2; P = 0.005) and decreased mean pulmonary arterial pressure and pulmonary vascular resistance (-5.3 mm Hg, P = 0.047; -4.7 Wood U, P = 0.003; respectively) at Week 12. Four patients in the placebo group (20%) and one in the vardenafil group (2.3%) had clinical worsening events (hazard ratio 0.105; 95% confidence interval, 0.012-0.938; P = 0.044). Vardenafil was associated with only mild and transient adverse events. Conclusions: Vardenafil is effective and well tolerated in patients with PAH at a dose of 5 mg twice daily.