That warning came from late-breaking results of the SIOVAC trial that were presented at the European Society of Cardiology meeting in Barcelona, Spain. At a Hot Line LBCT Session at the ESC Congress, Hospital General Universitario Gregorio Marañon–led researchers reported that off-label use of the drug led to worse clinical outcomes, including twice the risk of hospitalization, compared with placebo.
“Valvular disease is considered the next cardiac epidemic because of its strong association with age and the rapid aging of the population worldwide,” said principal investigator Javier Bermejo, MD, PhD. “The only established treatment is repair or replacement of the valve surgically or percutaneously. But symptoms often remain or reappear in the long-term. Residual pulmonary hypertension is the most important risk factor for death and disability after successful correction of the valvular lesion.”
Increased blood pressure in the pulmonary artery might persist after valve treatment, according to the study, which points out that sildenafil—which usually is used to treat erectile dysfunction—is frequently prescribed off-label in patients with retrograde pulmonary hypertension.
Conducted in 17 public hospitals and coordinated by the Spanish Network Centre for Cardiovascular Research (CIBERCV), the SIOVAC trial looked at whether sildenafil can improve long-term outcomes in patients with residual pulmonary hypertension after correction of a valvular lesion.
For the study, 200 patients were randomized to sildenafil 40 mg three times a day or placebo for 6 months. Prior to enrollment, patients were screened for contraindications to sildenafil, and cardiac catheterization was performed to confirm elevated pressure in the pulmonary artery.
The study team used a clinical composite score of all-cause death, hospital admission for heart failure, worsening exercise tolerance (measured by change in functional class), and feeling worse than when starting the medication (assessed by change in a self-assessment score) as the primary endpoint.
Much to the researchers’ surprise, clinical outcomes were worse in the sildenafil group compared with placebo; after 6 months, 33% of patients taking sildenafil and 15% of those receiving placebo had a worse composite clinical score than when the study began, with an odds ratio for improvement of 0.39.
“Compared to patients taking placebo, the chance for worse clinical outcomes—as defined by the combined clinical score—was more than twice as high in those taking sildenafil,” Bermejo points out. “We were unable to identify any particular subset of patients who could potentially benefit from sildenafil.”
The risk of hospital admission due to heart failure decompensation was doubled in patients taking sildenafil, the study determined. The hazard ratio for major clinical events, including death as well as hospitalization, was calculated to be 2.0.
“Long-term usage of sildenafil for treating residual pulmonary hypertension in patients with valvular heart disease should be avoided,” Bermejo emphasized. “The high incidence of events during the trial emphasized the need for further research to prevent and treat this complication in patients with valvular disease.”
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