Sildenafil for Pulmonary Hypertension

OBJECTIVE: To evaluate the efficacy of sildenafil for treatment of pulmonary hypertension. DATA SOURCES: Literature retrieval was accessed through MEDLINE (1977-March 2005), Cochrane Library, and International Pharmaceutical Abstracts (1977-March 2005) using the terms sildenafil and pulmonary hypertension. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated. Studies including >5 patients with primarily adult populations were included in the review. DATA SYNTHESIS: The treatment of pulmonary hypertension is challenging. Sildenafil has recently been studied as monotherapy and in combination with other vasodilators in the management of pulmonary hypertension. Eight hemodynamic studies and 12 clinical trials were reviewed (1 retrospective, 3 double-blind, 8 open-label). Sildenafil reduced pulmonary arterial hypertension and pulmonary vascular resistance/peripheral vascular resistance index and tended to increase cardiac output/cardiac index compared with baseline. Sildenafil was comparable to nitric oxide and at least as effective as iloprost or epoprostenol in terms of its pulmonary vasoreactivity. Combination therapy with iloprost, nitric oxide, or epoprostenol resulted in enhanced and prolonged pulmonary vascular effects. Clinical trials suggest that sildenafil improves exercise tolerance and New York Heart Association functional class, but large, randomized controlled trials are needed to confirm these findings. Overall, sildenafil was well tolerated. CONCLUSIONS: Overall, sildenafil is a promising and well-tolerated agent for management of pulmonary hypertension. Further well-designed trials are warranted to establish its place in the treatment of pulmonary hypertension.