Sildenafil appears safe, effective for long-term PAH treatment (SUPER-2) - PulmCCM
Dec 052011

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 2005which 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.

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  2 Responses to “Sildenafil appears safe, effective for long-term PAH treatment (SUPER-2)”

  1. The FDA approved dose of Sildenafil for PAH is only 20 mg TID. In this extension all patients were titrated up to 80 mg TID. That is 4x the FDA approved dose. Does Sildenafil work for these patients at the approved dose? The answer is we don’t know!

    Also we aren’t doing a very good job with these patients. About a third of them died by year 3, and 40% had a decrease in their functional class. Over half had a decrease in 6MWD as well.

    Why is it that only 18% were put on a second agent? Treating more aggressively could have possibly improved some of these patient’s outcomes.

  2. Very true, very true …

    authors addressed some of those concerns back here in 2006 …

    …But you’re right, if you use sildenafil 80 tid, you’re off label … and on your own for any adverse effects etc!

    Respectfully disagree that some bad outcomes here mean we aren’t doing a good job in general … plus, out of the 59 who died, 21 were on placebo … that’s the amazing thing to me, that they can get a placbeo controlled trial in PAH past an IRB when we know there are effective treatments.