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Dr. Gossage, a recommendation has been made by
the ACCP group with regard to the use of sildenafil. As
you know, since this publication, additional data have
been made available: In patients with PAH who have failed
or are not candidates for other available therapy, treatment
with sildenafil should be considered. Level of evidence:
low; benefit: intermediate; grade of recommendation: C.
What are your thoughts about this recommendation?
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 Jim
Gossage, MD
Professor of Medicine
Director of Pulmonary Vascular Diseases
Section of Pulmonary and Critical Care Medicine
Medical College of Georgia
Augusta, Georgia
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I basically agree with the ACCP recommendation, though
recently published trials will likely result in an upgrading
of the recommendation. The ACCP recommendations were based
on data published predominantly before 2003 and as such,
did not include any randomized trials. These studies collectively
showed an improvement in exercise tolerance and pulmonary
artery pressure, although a study by Bhatia and colleagues,
did not show a persistence of the hemodynamic effects.1
Following finalization of the ACCP recommendations, Sastry
and colleagues published a randomized crossover study
of 22 patients with PPH, which is the only
randomized trial to be published, thus far.2
They showed a 44% increase in exercise time with sildenafil,
and a statistically nonsignificant decrease in systolic
pulmonary artery pressure. The preliminary results of
the much-awaited SUPER-1 trial were presented at the recent
ACCP meeting. In this study, sildenafil patients showed
a 45 to 50 m increase in 6-minute walk distance, an improvement
in functional class, and a 5 mm Hg decrease in mean pulmonary
artery pressure (P = .09). If the full report of the trial
holds up to scrutiny, I would foresee that the recommendation
for sildenafil will be upgraded to B or perhaps even A.
Do you use this drug?
Yes. I have used sildenafil in perhaps 5% to 8% of my
patients with PAH. My results have been mixed but I have
had one excellent success in a woman with portopulmonary
hypertension who did not tolerate doses of epoprostenol
above 14 ng/kg/min because of side effects. Following
initiation of sildenafil at 25 mg tid, I was able to wean
her off epoprostenol over 3 months. At 22 months after
stopping
epoprostenol, she has had a persistent hemodynamic and
functional response.
How do you decide when to use it or add it?
Up to this point, I have been fairly cautious in my use
of sildenafil. I have reserved it mainly for patients
with WHO class III-IV PAH who meet one of the following
scenarios: 1) patients with intolerable side effects from
other treatments, such as the woman in the above vignette,
2) patients who have contraindications to other treatments,
3) patients in whom all other reasonable treatments have
failed, and 4)
patients who are not candidates for treatment with bosentan,
treprostinil, and epoprostenol. So I have basically followed
the ACCP recommendations for its use. I have also tried
sildenafil in one patient with PVOD, but it was not successful.
Following full publication of the SUPER-1 data, I would
expect to use it more frequently, especially in class
II patients.
References
1. Bhatia S, Frantz RP, Severson CJ, Durst
LA, McGoon MD. Immediate and long-term hemodynamic and
clinical effects of sildenafil in patients with pulmonary
arterial hypertension receiving vasodilator therapy. Mayo
Clin Proc. 2003;78(10):1207-13.
2. Sastry BK, Narasimhan C, Reddy NK,
Raja BS. Clinical efficacy of sildenafil in primary pulmonary
hypertension: a randomized, placebocontrolled, double-blind,
crossover study. J Am Coll Cardiol. 2004;43(7):1149-53.
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