Sildenafil looks to be reasonably safe and efficacious for long-term treatment of pulmonary arterial hypertension with NYHA class II or III symptoms, according to results of the SUPER-2 trial.
This was an extension of SUPER-1, reported in NEJM 2005, which was a 12-week randomized trial in people with PAH and NYHA II/III symptoms, in which those taking sildenafil had increased 6-minute walk distances and reduced mean pulmonary artery pressures compared to those taking placebo. The trial was only 12 weeks, so unsurprisingly there was no difference in clinical worsening between the groups.
In SUPER-2, they followed 277 of the original patients who were treated, including 183 patients who took sildenafil for 3 years. Most of the latter group (87%) were taking 80 mg sildenafil t.i.d.
- 3-year survival was between 68% and 79% (depending on whether you counted the ~37 censored patients as alive or not).
- 127 had an improved 6-minute walk distance.
- 46% maintained (n=86) or improved (n=81) functional class (54% had a decline in functional class).
- Only 18% were requiring a second agent; in almost all cases, this was bosentan.
Only 9 patients discontinued sildenafil due to perceived drug-related adverse events, but most patients (n=153) reported a perceived serious adverse event (including grand mal seizure, drug hypersensitivity, urticaria and angioedema, gastroesophageal reflux disease, posterior subcapsular cataract, and hypotension).
Looks like that stuff works …
Rubin LJ et al (the SUPER-2 Study Group). Long-term Treatment With Sildenafil Citrate in Pulmonary Arterial Hypertension. The SUPER-2 Study. CHEST 2011;140:1274-1283.
P.S. Pfizer funded the study, but did not participate in the study design, implementation, data analysis, or manuscript preparation, authors report. Most of the authors report receiving grants/honoraria/consulting fees from Pfizer.