"Wonder Drugs" May Work Wonders for Pulmonary Arterial Hypertension

The "wonder drugs" Gleevec (imatinib) and Viagra (sildenafil) make strange bedfellows, but they both appear to improve pulmonary function in patients with pulmonary arterial hypertension (PAH), report researchers here.

They described the Gleevec case in a letter published in the Sept. 29 New England Journal of Medicine.

In a last-ditch attempt to save a 61 year-old man with severe, familial idiopathic PAH that was rapidly progressing despite other therapies, Friedrich Grimminger, M.D., Ph.D., and colleagues at the University Hospital Giessen here gave him oral Gleevec (imatinib) 200 mg daily on a compassionate basis.

Gleevec, which is approved for chronic myeloid leukemia, has potent antiproliferative properties that the researchers hypothesized might be able to reverse the lung vascular remodeling - uncontrolled proliferation of the vascular wall - that is the underlying pathogenic mechanism of PAH.

The use of Gleevec in this situation was motivated in part by experimental studies in animals performed by the authors. "We have described the successful use of imatinib in two well-established experimental models of progressive pulmonary arterial hypertension; this treatment resulted in virtually complete reversal of lung vascular remodeling, pulmonary hypertension, and right-sided heart hypertrophy" they said. These studies are in press in the Journal of Clinical Investigation.

In contrast, Viagra (sildenafil), which has also been shown in randomized placebo-controlled trials to improve function in patients with PAH, works by prolonged vasodilation, allowing better oxygenation.

In addition to taking Gleevec, the patient described in the case report continued on his other medications, including Tracleer (bosentan), Ventavis (iloprost), Viagra, oral anticoagulants and diuretics.

After three months of Gleevec, the patient's condition "improved impressively," as indicated by improved exercise capacity, hemodynamics, mean pulmonary artery pressure, cardiac index, and New York Heart Association (NYHA) functional class.

Although this was only a single case report, Dr. Grimminger and colleagues had previously demonstrated in a randomized placebo controlled trial (SUPER-1) that patients who received 80 mg of Viagra three times daily increased six-minute walk results by 50 meters after 12 weeks. Patients on 40 mg Viagra t.i.d. increased their six-minute distance by 46 meters, and those at a 20 mg three times daily dose increased by 45 meters. The difference were significant at P < .001.

Among all patients on Viagra in that study, 35% had a functional class improvement, compared with 7% of patients in the placebo group, and there was a non-significant trend toward reduction in mean pulmonary arterial pressure.