Adempas Improves Blood Flow Parameters in PH-HFpEF Trial
Trial examines those with PH and heart failure with preserved ejection fraction
Researchers say that further study is needed to determine the effect of Adempas on clinical outcomes like exercise capacity.
The study, “Riociguat in pulmonary hypertension and heart failure with preserved ejection fraction: the haemoDYNAMIC trial,” was published in the European Heart Journal. The work was funded by Bayer, which markets Adempas.
HFpEF is a condition where the heart cannot adequately pump blood out to the body; most people with HFpEF develop pulmonary hypertension (PH-HFpEF). Available treatments have limited ability to improve morbidity and mortality outcomes in PH-HFpEF.
A team led by scientists at the Medical University of Vienna conducted a Phase 2 clinical trial called DYNAMIC (NCT02744339) to evaluate Adempas in PH-HFpEF. Adempas works to lower blood pressure by prompting blood vessels to widen through modulation of a protein called soluble guanylate cyclase.
The trial and its results
A total of 114 people with PH-HFpEF were randomly assigned to take Adempas or a placebo for 26 weeks, half a year. Among the participants, about three-quarters were female, and the mean age was 71.4 years.
Adempas was initially given at a dose of 0.5 mg three times daily; this dose was gradually increased to 1.5 mg over the first eight weeks of the study based on clinical condition and blood pressure. About two-thirds of participants reached the maximum dose.
The study’s main goal was to assess the impact of treatment on cardiac output (CO), a measure of how much blood the heart pumps in a minute. After 26 weeks, average CO increased by 0.37 L/min in patients on Adempas, whereas for patients on placebo, average CO decreased by 0.11 L/min.
Adempas also outperformed placebo at reducing certain measures associated with blood pressure in the lungs, namely transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR). TPG is the difference between mean pulmonary artery pressure and pressure in the heart’s top left chamber, whereas PVR refers to how hard blood has to push to flow through the blood vessels.
Other blood flow measures — pulmonary arterial wedge pressure (PAWP) and systemic vascular resistance (SVR) — showed no difference between the groups. Measures of exercise capacity and life quality also did not significantly differ.
“Further studies are required to determine whether the effect of improved CO in response to [Adempas] will translate into a better clinical outcome in the specific phenotype of PH-HFpEF,” the team wrote.
About one-third of patients in the Adempas group reported treatment-related side effects; the most common were swelling, shortness of breath, and low blood pressure. One participant on Adempas died of cardiac arrest during the trial, but this was judged unrelated to the therapy.
In total, 31% of patients on Adempas discontinued the trial early, as did 14.3% of those in the placebo group, with adverse events listed as a reason for discontinuation.
“Overall, riociguat had a favourable safety profile with respect to patients who completed the study. Nevertheless, higher dropout rates demand careful monitoring in future trials,” the researchers wrote.