Immediate and long-term hemodynamic and clinical effects of sildenafil in patients with pulmonary arterial hypertension receiving vasodilator therapy

Objective: To determine the immediate and long-term effects of adding sildenafil, a phosphodiesterase-5 inhibitor, to the medical regimen of patients with pulmonary arterial hypertension (PAH). Patients and Methods: Thirteen patients with PAH received empirical adjunctive sildenafil treatment at the Mayo Clinic in Rochester, Minn, between November 1, 2000, and August 31, 2001. All received a 25-mg dose of sildenafil, increased by 25 mg at 8-hour intervals, if tolerated, up to 100 mg during hemodynamic monitoring for 24 to 48 hours. Long-term effects on right heart hemodynamics were assessed by noninvasive right ventricular systolic pressure, right ventricular index of myocardial performance, and a 6-minute walk test. Results: Sildenafil significantly increased cardiac output (CO) (P=.04) and decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and mean arterial pressure (P<.01) at peak measurements (obtained 1-2 hours after highest dose). At trough measurements (obtained 8 hours after highest dose), sildenafil significantly decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, and mean arterial pressure (P=.01). Ten patients discharged from the hospital were taking the highest-tolerated dose of sildenafil every 8 hours. The right ventricular systolic pressure and right index of myocardial performance showed no significant improvement at follow-up (117±70 days), although concomitant treatment with epoprostenol could be tapered in 2 patients. Changes in New York Heart Association classes were inconsistent, and improvements in the 6-minute walk test were not significant. Conclusion: Sildenafil has an immediate pulmonary vasodilator effect in patients already receiving vasodilators for PAH. Its long-term effects on right heart function and functional status are equivocal. A large, prospective, well-designed study is needed to determine the effects of sildenafil on PAH, both in untreated and concurrently treated patients.