Elsevier

Mayo Clinic Proceedings

Volume 78, Issue 10, October 2003, Pages 1207-1213
Mayo Clinic Proceedings

Original Article
Immediate and Long-term Hemodynamic and Clinical Effects of Sildenafil in Patients With Pulmonary Arterial Hypertension Receiving Vasodilator Therapy

https://doi.org/10.4065/78.10.1207Get rights and content

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.

Section snippets

PATIENTS AND METHODS

The treatment regimens of 13 patients with PAH, managed by the Pulmonary Hypertension Clinic at the Mayo Clinic in Rochester, Minn, were modified empirically between November 1, 2000, and August 31, 2001, to include sildenafil. This study is a retrospective review of these patients. Sildenafil was used to augment treatment efficacy or permit down-titration of medications associated with adverse effects, expense, and/or inconvenience. All patients had undergone recent transthoracic

Patient Characteristics

The medical records of 13 patients were reviewed (Table 1). The mean ± SEM age was 55.1±9.8 years; 10 patients were women. Eleven patients had primary PAH, as defined by World Health Organization criteria. One patient had chronic thromboembolic pulmonary hypertension supported by history and prior ventilation-perfusion images, and 1 patient had portopulmonary hypertension attributed to primary sclerosing cholangitis. Of the 13 patients, 2 were in NYHA class I, 4 were in NYHA class II, and 7

DISCUSSION

During the past decade, there have been substantial advances in the understanding and management of PAH. Unfortunately, limited efficacy, adverse effects, and high costs often characterize current therapies. The goal of this study was to determine the short-term and long-term effects of sildenafil when added to the existing medical regimen of patients with PAH.

The addition of sildenafil significantly improved CO, mPAP, PASP, and PVR 1 to 2 hours after administration of the highest-tolerated

CONCLUSION

Oral sildenafil has an immediate pulmonary vasodilator effect in patients already treated with vasodilators for pulmonary hypertension. However, its effect on functional status and right heart function during longer-term administration in this small group was unsubstantial. Because of the simplicity of administration and apparent relative safety of sildenafil, it is a potentially attractive option as adjunctive therapy to current treatment strategies if a sufficient level of efficacy were

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      Among them, sildenafil is a first-line drug for the treatment of PAH, in monotherapy or in association with endothelin receptor antagonists [4]. Most of the side effects of sildenafil are secondary to a loss of selectivity for PDE5 (e.g., visual disturbances) and/or for the pulmonary circulation (e.g., systemic hypotension, headache, flushing, nasal congestion) [6–8]. In addition, although the hepatic toxicity of sildenafil is rare, some cases of sildenafil-associated hepatotoxicity have been reported in the last decade [9].

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