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Clinical Question:
Does sildenafil (VIAGRA) improve outcomes in adults with pulmonary arterial
hypertension?
Bottom Line:
Sildenafil improves exercise capacity, WHO functional class, and
hemodynamics in patients with symptomatic pulmonary arterial hypertension.
Reference:
Galie N, Ghofrani HA, Torbicki A, et al, for the Sildenafil Use in Pulmonary
Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for
pulmonary arterial hypertension. N Engl J Med 2005; 353:2148-57.
Study Design:
Randomized controlled trial (double-blinded)
Synopsis:
Sildenafil inhibits phosphodiesterase type 5, an enzyme that metabolizes
cyclic guanosine monophosphate, thereby enhancing the cyclic guanosine
monophosphate-mediated relaxation and growth inhibition of vascular
smooth-muscle cells, including those in the lung. In this double-blind,
placebo-controlled study, we randomly assigned 278 patients with symptomatic
pulmonary arterial hypertension (either idiopathic or associated with
connective-tissue disease or with repaired congenital systemic-to-pulmonary
shunts) to placebo or sildenafil (20, 40, or 80 mg) orally three times daily
for 12 weeks. The primary end point was the change from baseline to week 12
in the distance walked in six minutes. The change in mean pulmonary-artery
pressure and World Health Organization (WHO) functional class and the
incidence of clinical worsening were also assessed, but the study was not
powered to assess mortality. Patients completing the 12-week randomized
study could enter a long-term extension study. The distance walked in six
minutes increased from baseline in all sildenafil groups; the mean
placebo-corrected treatment effects were 45 m (+13.0 percent), 46 m (+13.3
percent), and 50 m (+14.7 percent) for 20, 40, and 80 mg of sildenafil,
respectively (P<0.001 for all comparisons). All sildenafil doses reduced the
mean pulmonary-artery pressure (P=0.04, P=0.01, and P<0.001, respectively),
improved the WHO functional class (P=0.003, P<0.001, and P<0.001,
respectively), and were associated with side effects such as flushing,
dyspepsia, and diarrhea. The incidence of clinical worsening did not differ
significantly between the patients treated with sildenafil and those treated
with placebo. Among the 222 patients completing one year of treatment with
sildenafil monotherapy, the improvement from baseline at one year in the
distance walked in six minutes was 51 m. |