Sildenafil significantly improves exercise tolerance, cardiac output, and quality-of-life in patients with primary pulmonary hypertension (PPH), reports a study from India.
Primary pulmonary hypertension is an uncommon disorder that can lead to heart failure and death. Current treatment approaches are limited, but some nonrandomised data suggest a benefit with sildenafil.
In this randomised, double-blind, placebo-controlled, crossover trial, BKS Sastry, DM, and colleagues, Department of Cardiology, CARE Hospital, Hyderabad, India, evaluated the efficacy of sildenafil in 22 patients (aged 16 to 55 years) with PPH enrolled in the study between September 2002 and December 2002. Pulmonary artery systolic pressure and mean pulmonary artery pressure were more than 70 mm Hg and 30 mm Hg, respectively, in all patients.
After clinical evaluation that included a treadmill exercise test and Doppler echocardiography, 10 patients were first randomised to sildenafil (25-100 mg, based on body weight, 3 times daily) and 12 to placebo. After 6 weeks, the patients were evaluated again and crossed over to the alternate therapy. Final evaluation was done 6 weeks later. Primary end point evaluated was change in exercise time on the treadmill using the Naughton protocol; secondary end points included changes in pulmonary artery systolic pressure, cardiac output, and change in quality-of-life.
At the end of the first 6 weeks, the patients treated first in the placebo group had no significant difference in exercise time compared to baseline. After crossover to sildenafil, exercise increased significantly at the end of the next 6 weeks (from 452.1 + 165.6 s to 687 + 243.9 s, P < .0001). Patients initially treated with sildenafil had a significant increase in exercise time at the end of the first 6 weeks compared to baseline (from 451.6 + 189.6 s to 698.1 + 272.9 s, P < .001). When crossed over into the placebo treatment, the exercise time decreased significantly at the end of the next 6 weeks (to 527.4 + 181.6, P < .005), but remained significantly higher from baseline.
Overall, exercise time significantly increased from 475 + 168 s at the end of the placebo phase to 686 + 224 s at the end of the 6 weeks on sildenafil (P < .0001). Sildenafil was also associated with significant improvement in cardiac index (P < .0001), significant improvement in quality-of-life measures (dyspnoea and fatigue), and a nonsignificant decrease in pulmonary artery systolic pressure (P = .09).
Based on the significant improvement in exercise tolerance, cardiac output, and quality-of-life measures, the authors conclude that sildenafil "may be a reasonable first-line therapy" in patients with PPH. They emphasize, however, that "further studies are required to establish long-term safety and efficacy of sildenafil, its additive benefit with other drugs, if any, and its role in secondary forms of pulmonary artery hypertension."