Sildenafil should be avoided in residual pulmonary hypertension after corrected valvular heart disease
Sildenafil should not be used to treat residual pulmonary hypertension in patients with corrected left valvular heart disease, according to the results of a late-breaking trial presented at the European Society of Cardiology (ESC) Congress 2017.
“We saw that a greater proportion of patients taking sildenafil experienced worse clinical outcomes than those receiving placebo,” said Dr Javier Bermejo of the Hospital General Universitario Gregorio Marañon in Madrid, Spain, lead investigator of the SIOVAC (Sildenafil for Improving Outcomes after Valvular Correction) trial. “Patients receiving sildenafil also had twice the number of hospital admissions due to heart failure compared with placebo recipients.”
The phosphodiesterase (PDE)-5 inhibitor sildenafil, indicated for treatment of erectile dysfunction, is also commonly used to treat pulmonary arterial hypertension. However, use of sildenafil in patients with pulmonary hypertension due to left heart disease is not well established, with previous studies addressing this showing discordant results.
“Pulmonary hypertension is a high-risk complication for valvular heart disease even after the regional valvular lesion has been corrected,” Bermejo explained. “This type of pulmonary hypertension is a well-established risk factor for disability and increased mortality in the long-term. However, there is currently no treatment for these patients.”
Bermejo and colleagues conducted the SIOVAC trial to specifically assess whether sildenafil could improve outcomes in patients with residual pulmonary hypertension after successful correction of a valvular lesion. The double-blind, placebo-controlled clinical trial included 200 patients from 18 tertiary-care hospitals in Spain, who were randomized to receive sildenafil 40 mg three times daily or placebo.
After 6 months of follow-up, a significantly higher proportion of patients receiving sildenafil experienced worsening of clinical outcomes vs those receiving placebo, as measured by a composite clinical score of all-cause death, hospital admission for heart failure, worsening exercise tolerance, and self-assessed worsening (33 vs 15 percent; odds ratio [OR] for improvement, 0.39; p<0.001).
Patients receiving sildenafil also had a significantly higher risk of major clinical events (death or hospitalizations due to heart failure) vs placebo (hazard ratio, 2.0; p=0.044). In particular, sildenafil led to a significant increase in hospital admissions due to heart failure vs placebo (OR, 0.43; p=0.035). There was no difference in the risk of death between the two treatment arms (deaths, 3 patients receiving sildenafil vs 2 patients receiving placebo; p=0.63).
“Based on these results, off-label use of sildenafil in this specific population of patients should be discouraged,” Bermejo advised.
“The message from the SIOVAC trial is very clear. Patients receiving sildenafil 40 mg three times daily did worse,” said Dr Irene Lang of the Medical University of Vienna, Vienna, Austria, who discussed the results. “Although SIOVAC is a negative study, it is very important because it shows what we should not do – treat pulmonary hypertension due to left heart disease with sildenafil.”