NEW YORK (Reuters Health) – Treating patients with pulmonary arterial hypertension with more than one class of pulmonary vasodilator does not decrease mortality or slow progression of the disease, according the results of meta-analysis published in the American Journal of Cardiology online August 25th.
“Combination therapy does not offer an advantage over monotherapy apart from modestly increasing exercise capacity,” conclude Dr. David Langleben, with Jewish General Hospital and McGill University in Montreal, Quebec, Canada, and colleagues in Israel.
The authors note that pulmonary arterial hypertension (PAH) remains incurable, but novel pharmacologic agents for treating the condition have been developed. Currently, the three main drug classes licensed for PAH are prostanoids (iloprost, treprostinil), endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil).
As these drug classes have different mechanisms of action, combination might improve outcomes, the team points out. However, several randomized clinical trials comparing monotherapy with the addition of a placebo or another active agent have had conflicting results. The investigators therefore identified six such clinical trials and performed a meta-analysis of the data.
They found that although relative risks seemed to favor one strategy or the other, there was actually no statistically significant difference between monotherapy and combination therapy in terms of mortality risk, hospital admissions for worsening PAH, escalation of therapy, or improvement in NYHA functional class.
Only in the 6-minute walk test was there a significant difference: a weighted mean increase of 25.2 meters with combination therapy versus monotherapy.
In discussing the results, Dr. Langleben and colleagues point out that while current guidelines suggest that any form of combination therapy is acceptable for treating patients with PAH, some combinations might be more beneficial than others.
From the limited evidence available, however, it is not possible to say which combination might give the best results. “It is also unlikely,” they write, “that this question will ever be answered definitively because this would require a large multi-arm trial and open cooperation among different pharmaceutical companies.”
They therefore conclude, “When commencing combination therapy, the physician must rely on clinical judgment alone.”
Reference:
Meta-Analysis of Monotherapy Versus Combination Therapy for Pulmonary Arterial Hypertension
Am J Cardiol 2011.
