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).


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 < or = .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.


CONCLUSIONS
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.
Bhatia
Sundeep
S
Department of Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA.
Frantz
Robert P
RP
Severson
Cathy J
CJ
Durst
Louise A
LA
McGoon
Michael D
MD
D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011687:Purines; D012189:Retrospective Studies; D000068677:Sildenafil Citrate; D013450:Sulfones; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate