LETTER TO THE EDITOR
Clinical efficacy of sildenafil in primary pulmonary hypertension
Ronald J. Oudiz, MD, FACC* and
Karlman Wasserman, MD, PhD
* Division of Cardiology, Saint John's Cardiovascular Research Center, Harbor–UCLA Medical Center, Torrance, CA 90502 (Email: oudiz{at}humc.edu).
In the report entitled "Clinical Efficacy of Sildenafil in Primary Pulmonary Hypertension: A Randomized, Placebo-Controlled, Double-Blind, Crossover Study" (1) the investigators cite an impressive short-term improvement in exercise capacity in patients with pulmonary arterial hypertension (PPH) and who are taking daily oral sildenafil. The researchers compare their patients' improvement in exercise capacity with sildenafil to that of prior studies of oral bosentan, oral beraprost, and aerosolized iloprost. Although their earlier uncontrolled study, which used 6-min walk testing, suggested an improvement in walk distance of 40% over baseline (2), their more recent placebo-controlled study, which used submaximal exercise duration on a treadmill, showed a 44% increase in exercise time. This improvement was favorably compared to bosentan, beraprost, and iloprost, whose improvement in 6-min walk distance ranged from only 12% to 21%.
We applaud the investigators' choice of measuring exercise endurance over a 6-min walk distance as a measure of exercise capacity end point for patients with PPH. However, we believe that these comparisons of sildenafil with other pulmonary vascular drugs should be interpreted cautiously, because: 1) the patient population in each study was not the same and 2) the 6-min walk distance and treadmill exercise endurance times are not comparable in terms of percent change. Oga et al. (3) have shown that submaximal exercise endurance time is a much more sensitive indicator of change in exercise capacity than the 6-min walk distance or peak VO2. In that study, a 19% increase in exercise duration paralleled a much smaller, although significant, 1% increase in 6-min walk distance after treatment of chronic obstructive pulmonary disease patients with an inhaled anticholinergic agent.
In measuring exercise capacity, the percent improvement in endurance time likely depends on the level of exercise, particularly with respect to the chosen exercise protocol (constant vs. incremental work rate protocol). Thus, in this latest sildenafil study, the 44% increase in exercise duration probably overestimates the improvement that would have been seen had the 6-min walk distance been used to measure exercise capacity.
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1. Sastry BK, Narasimhan C, Reddy NK, Raju BS. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study J Am Coll Cardiol 2004;43:1149-1153.[Abstract/Free Full Text]
2. Sastry BK, Narasimhan C, Reddy NK, et al. A study of clinical efficacy of sildenafil in patients with primary pulmonary hypertension Indian Heart J 2002;54:410-414.[Medline]
3. Oga T, Nishimura K, Tsukino M, Hajiro T, Ikeda A, Izumi T. The effects of oxitropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease. A comparison of three different exercise tests Am J Respir Crit Care Med 2000;161:1897-1901.[Abstract/Free Full Text]
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