A DUE: Fixed-Dose Combination Beats Monotherapy in Reducing PVR in PAH

Patients with pulmonary arterial hypertension (PAH) had approximately double the reduction in pulmonary vascular resistance (PVR) when taking macitentan and tadalafil together in a single fixed-dose combination (FDC) tablet than either drug alone, according to research presented at ACC.23/WCC.

The prospective, multicenter, double-blind study randomized 187 patients with class II and III PAH to macitentan 10 mg monotherapy (n=35), macitentan 10 mg plus tadalafil 40 mg FDC (n=108) or tadalafil 40 mg monotherapy (n=44). Most patients (about 80%) were women, with an average age ranging from 49-53 years; about half were treatment naïve.

The primary endpoint of change in PVR at Week 16 as a ratio of baseline for the comparison of FDC against macitentan was –45% and –23%, respectively, a 29% greater reduction (p<0.0001). For the comparison of FDC against tadalafil it was –44% vs. –22%, respectively, a 28% greater reduction (p<0.0001).

For the secondary endpoint of change in the 6-minute walking distance, there was a trend for a clinically relevant improvement with the FDC. In the comparison of FDC against macitentan, the mean change at Week 16 was 52.9 and 38.5, respectively, and in the comparison of FDC against tadalafil it was 43.4 and 15.9.

Kelly Chin, MD, et al., noted that nine patients in the FDC group and two in the tadalafil group discontinued the assigned treatment due to adverse events, with anemia, hypotension and swelling among the most common side effects. Overall, the FDC was well tolerated with a safety profile similar with the individual drugs.

“Across many studies, we’re seeing that more is better in terms of lowering PVR, and what we get with one medication is, for many patients, just not enough,” said Chin. “I would strongly recommend combination therapy with two medications initially for the majority of patients, and this combination has significant evidence that it’s effective and well tolerated."

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Statins, Pulmonary Hypertension, Hypertension

Keywords: ACC Annual Scientific Session, ACC23, Tadalafil, Sulfonamides, Familial Primary Pulmonary Hypertension, Pyrimidines, Pulmonary Arterial Hypertension, Hypertension, Pulmonary

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