Scleroderma

Neither aspirin nor simvastatin improved outcomes for patients with pulmonary arterial hypertension in a phase II safety and efficacy trial recently published online in Circulation and simultaneously presented at the annual meeting of the American Thoracic Society.

The primary end point of 6-minute walk distance did not increase after 6 months of aspirin therapy and actually decreased after 6 months of simvastatin therapy, indicating that neither agent should be used as an add-on therapy in PAH, said Dr. Steven M. Kawut of Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, and his associates.

A recent animal study showed that aspirin decreased pulmonary artery pressure, reduced right ventricular hypertrophy, and improved survival, and several recent studies showed that statins were effective in animal models of pulmonary hypertension. Dr. Kawut and his associates in the ASA-STAT Study Group designed their phase II clinical trial to test the safety and efficacy of both agents against matching placebos, intending to enroll 100 subjects with PAH.

The study, however, was terminated after only 65 subjects had been randomized because an interim analysis showed "a high likelihood of not rejecting the null hypothesis for the simvastatin arm even if fully recruited," they wrote. The investigators reported their findings for those 65 subjects.

The patients’ mean age was 50 years, and 86% were women. Approximately 52% had idiopathic PAH, 19% had PAH associated with systemic sclerosis, 15% had PAH associated with other connective tissue diseases, 9% had congenital systemic-to-pulmonary shunts, and 5% had heritable PAH.

The primary outcome measure was 6-minute walk distance after 6 months of treatment, after adjustment for 6-minute walk distance at baseline.

Patients who received aspirin therapy showed no improvement in this measure, compared with those who received placebo. They also showed no improvement in median Borg dyspnea scores after the walk test, in any scales of the SF-36, or in World Health Organization functional class. And there was no difference between the two groups in time to clinical worsening, Dr. Kawut and his associates said.

Similarly, patients who received simvastatin showed no improvement in 6-minute walk distance after 6 months of treatment, compared with those who received placebo. In fact, the active drug may have reduced this distance, although the number of subjects was not sufficient to detect a statistically significant difference. Moreover, the median Borg dyspnea scores after the walk test tended to be higher in subjects who took simvastatin than in those who took placebo, suggesting greater breathlessness.

As with aspirin, there were no differences on any scales of the SF-36 or in WHO functional class between the subjects who took simvastatin and those who took placebo, the investigators said (Circulation 2011 May 19 [doi:10.1161/CIRCULATIONAHA.110.015693]).

"There was a possible increased risk of major bleeding associated with aspirin use," they noted, but again, the number of subjects was not sufficient to make this determination definitively.

"On the basis of these finding, neither drug can be recommended for the treatment of PAH," Dr. Kawut and his colleagues said.

The study was funded by the National Institutes of Health and the National Center for Research Resources. Aspirin and matching placebo were provided free of charge by Bayer Healthcare. Additional support was provided by Merck. Dr. Kawut and his associates reported ties to numerous industry sources.

Source: Moon, M. (2011),  "Aspirin, Simvastatin Not Effective for Pulmonary Arterial Hypertension"; source article can be viewed here.