GIESSEN, GERMANY—When blood-vessel remodeling occurs as a result of pulmonary embolization, progressive increases in vascular resistance may develop, leading to chronic thromboembolic pulmonary hypertension (CTEPH). Unfortunately, only a few such cases can be treated with thromboendarterectomy. A small study now demonstrates that oral sildenafil can significantly improve long-term pulmonary hemodynamics and exercise tolerance in patients with inoperable CTEPH.[1]

For patients with this disorder, “there is not very much to offer as a therapeutic option,” remarked primary author Hossein Ardeschir Ghofrani, MD. “Only a minor fraction of them—about one fourth—is eligible for surgery.” Peripheral embolizations are inaccessible to surgery; as a consequence, pulmonary thromboendarterectomy “can be applied only to those patients who have very central thrombi,” explained Dr. Ghofrani, who is an Assistant Professor of Internal Medicine at Justus-Liebig-University in Giessen, Germany.

Previous work by Dr. Ghofrani and colleagues showed sildenafil’s efficacy in pulmonary arterial hypertension. The new study extends their findings to patients with CTEPH; in this group, sildenafil produced improvements in hemodynamic parameters—in particular, a reduction in pulmonary vascular resistance. “But also,” said Dr. Ghofrani, “patients’ exercise capacity and quality of life changed favorably.” He remarked, “Results have been very promising. I think this is an emerging therapy in the field of pulmonary hypertension.”

LONG-TERM SILDENAFIL IMPROVED HEMODYNAMICS

Dr. Ghofrani and colleagues recruited 12 patients with nonoperable CTEPH who met at least two of the following criteria: subjective clinical worsening, greater than 20% deterioration in six-minute walk distance, signs of increased right heart load, or syncope. All of the patients recruited had severe pulmonary hypertension, with a mean pulmonary artery pressure of 52.6 mm Hg, central venous pressure of 11.0 mm Hg, pulmonary vascular resistance index of 1,935 dyn · s · cm–5 · m2, and cardiac index of 2.0 L/min/m2. Average six-minute walk distance was 312 m.

The patients underwent acute vasodilator testing with inhaled nitric oxide, and then hemodynamic parameters were remeasured. After these parameters returned to baseline, each patient was given a single oral dose of sildenafil; hemodynamic parameters were recorded a third time one hour later. Nitric oxide and oral sildenafil were both found to lower the pulmonary vascular resistance index (by a mean of 12.7% and 21.5%, respectively).

Following baseline testing, patients then received oral sildenafil (50 mg three times daily) for a mean of 6.5 months. Long-term administration of sildenafil lowered the mean pulmonary artery pressure to 44.9 mm Hg, the central venous pressure to 4.8 mm Hg, and the pulmonary vascular resistance index to 1,361 dyn · s · cm–5 · m2. The mean cardiac index increased to 2.4 L/min/m2, and the mean six-minute walk distance increased by 54 m to 366 m.

RESULTS WARRANT LARGER TRIALS

“I think still we have to wait for the results of placebo-controlled, larger trials before we can make recommendations regarding the use of sildenafil in this field,” Dr. Ghofrani admitted, given that his group’s study was limited by its small sample size and open-label design. “Nevertheless,” he emphasized, “the changes seen in the patients are so consistent and so impressive that we think this study [justifies] a larger, controlled multicenter study.”

—Mimi Zucker, PhD

Reference
1. Ghofrani HA, Schermuly RT, Rose F, et al. Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med. 2003;167:1139-1141.

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