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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^sup -1^.m^sup -2^; P = 0.005) and decreased mean pulmonary arterial pressure and pulmonary vascular resistance (-5.3 mm Hg, P = 0.047; 24.7 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.
Keywords: pulmonary hypertension; phosphodiesterase inhibitors; vardenafil; exercise; hemodynamics
Pulmonary arterial hypertension (PAH) is a progressive debilitating disease characterized by an increase in pulmonary vascular resistance, often leading to right heart failure and premature death (1, 2). The pathogenesis of PAH is poorly understood, but an imbalance between vascular cell proliferation and apoptosis, excess vasoconstriction, inflammation, and in situ thrombosis all contribute to narrowing or obliteration of the pulmonary arteriolar lumens and increased pulmonary vascular resistance (3-5).
There is no cure for PAH; however, the currently approved treatment options (i.e., prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors) improve symptoms, exercise capacity, and clinical outcome. These treatment options, however, are limited either by parenteral or inhaled delivery systems, the need for laboratory monitoring, frequent dosing schedules or dosing uncertainties, and elevated costs (6).
PAH is associated with impaired release of...