The use of Revatio (sildenafil) to treat pulmonary hypertension in patients with valvular heart disease leads to worse clinical outcomes compared to placebo, results from a new clinical trial indicate.
Results from the Phase 4 SIOVAC trial (NCT00862043) were presented at a Hot Line Late Breaking Clinical Trials (LBCT) Session at the 2017 ESC Congress in Barcelona, hosted by the European Society of Cardiology.
Revatio is a potent vasodilator, generally safe and well-tolerated by patients. The drug is used in the treatment of pulmonary hypertension — a disease associated with increased blood pressure in the pulmonary artery.
Patients with valvular heart disease are often prescribed Revatio as the disease can lead to the development of pulmonary hypertension.
Valvular disease develops due to dysfunction of heart valves that work to keep the blood flowing in one direction. When these valves malfunction, it creates pressure in the left side of the heart, which subsequently causes high pressure in lung blood vessels. In some cases, the condition can be treated with a valve repair or substitution, but if not, then persistent pulmonary hypertension can develop.
“The only established treatment is repair or replacement of the valve surgically or percutaneously,” Javier Bermejo, cardiologist at Hospital General Universitario Gregorio Marañon and the study’s principal investigator, said in a press release. “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.”
The SIOVAC trial aimed to determine whether Revatio could improve the long-term condition of patients with residual pulmonary hypertension after the treatment of valvular lesions. Patients underwent catheterization to confirm the presence of pulmonary hypertension.
In total, 200 patients were recruited for the trial and received either 40 mg of Revatio three times a day or placebo, for a total of six months.
The primary endpoint of the trial was a composite score which consisted of four factors: all-cause mortality, frequency of hospital admission, decreased exercise tolerance, and feeling worse since the initiation of the drug. The latter was evaluated using a self-assessment score.
Results from the trial showed that the composite score was significantly worse in patients who took Revatio compared to patients in the placebo group. In fact, after six months, 33 percent of patients taking Revatio and 15 percent of those in the placebo group had a worse composite clinical score compared to the start of the trial.
“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. We were unable to identify any particular subset of patients who could potentially benefit from sildenafil,” Bermejo said.
In addition, patients who took Revatio experienced more frequent heart failure-related hospital admissions. In addition, the occurrence of adverse events, death, and hospital admission took place earlier in patients taking Revatio compared to patients receiving placebo.
“Long-term usage of sildenafil for treating residual pulmonary hypertension in patients with valvular heart disease should be avoided,” Bermejo said. “The high incidence of events during the trial emphasizes the need for further research to prevent and treat this complication in patients with valvular disease.”