Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study.
OBJECTIVE
In a randomized, double-blind, crossover design, we compared the efficacy of sildenafil with placebo in patients with primary pulmonary hypertension (PPH). The primary end point was the change in exercise time on treadmill using the Naughton protocol. Secondary end points were change in cardiac index and pulmonary artery systolic pressure as assessed by Doppler echocardiography and quality of life (QOL) as assessed by a questionnaire.


BACKGROUND
Primary pulmonary hypertension is a disorder with limited treatment options. Uncontrolled studies had shown sildenafil to be beneficial in the treatment of PPH.


METHODS
After initial clinical evaluation, including Doppler echocardiography and treadmill exercise test, patients were randomized to placebo or sildenafil with dosages ranging from 25 to 100 mg thrice daily on the basis of body weight. The evaluation was repeated after six weeks. Then patients were crossed over to alternate therapy. Final evaluation was performed after another six weeks of treatment.


RESULTS
Twenty-two patients completed the study. Exercise time increased by 44% from 475 +/- 168 s at the end of placebo phase to 686 +/- 224 s at the end of sildenafil phase (p < 0.0001). With sildenafil, cardiac index improved from 2.80 +/- 0.9 l/m2 to 3.45 +/- 1.1 l/m(2) (p < 0.0001), whereas pulmonary artery systolic pressure decreased insignificantly from 105.23 +/- 17.82 mm Hg to 98.50 +/- 24.38 mm Hg. There was significant improvement in the dyspnea and fatigue components of the QOL questionnaire. During the placebo phase, one patient died and another had syncope. There were no serious side effects with sildenafil.


CONCLUSIONS
Sildenafil significantly improves exercise tolerance, cardiac index, and QOL in patients with PPH.
Sastry
B K S
BK
Department of Cardiology, CARE Hospital, Hyderabad, India. bkssastry@hotmail.com
Narasimhan
C
C
Reddy
N Krishna
NK
Raju
B Soma
BS
D000293:Adolescent; D000328:Adult; D000368:Aged; D002306:Cardiac Volume / Q000187:drug effects; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011687:Purines; D011788:Quality of Life; D000068677:Sildenafil Citrate; D013450:Sulfones; D013599:Systole / Q000187:drug effects; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate