Macitentan and Tadalafil Combination Improves PVR in Pulmonary Arterial Hypertension

This article is part of Pulmonology Advisor‘s coverage of the CHEST 2019 meeting, taking place in New Orleans, LA. Our staff will report on medical research related to asthma, COPD, critical care medicine, and more conducted by experts in the field. Check back regularly for more news from CHEST 2019.

NEW ORLEANS — Combination therapy consisting of once-daily macitentan and tadalafil was associated with reductions in pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH), according to research findings presented at the CHEST Annual Meeting 2019, held October 19 to 23, 2019, in New Orleans, Louisiana.

The presented research included findings from the prospective, multicenter, single-arm, open-label, phase 4 OPTIMA (ClinicalTrials.gov Identifier: NCT02968901) trial. Patients in the study had newly diagnosed PAH, were in World Health Organization functional class 2 and 3, and had no history of prior PAH therapy. The study treatment consisted of once-daily macitentan 10 mg and once-daily tadalafil 20 mg, with the tadalafil dose increasing to 40 mg after 8±3 days. The primary end point included reduction in mean PVR, which was assessed at week 16. Safety was also assessed for the 16 weeks until study termination.

During the trial, the median duration of exposure to macitentan and tadalafil was 605.5 days. In the 46 patients who were enrolled and treated in OPTIMA, there was a 47% reduction in the mean PVR at 16 weeks compared with baseline (geometric mean ratio, 0.53; 95% CI, 0.47-0.59; p2.5 L/min/m²; mean right atrial pressure, 440 m; NT-proBNP, 65%).

“Observing a PVR reduction of this magnitude is clinically meaningful,” study investigator Olivier Sitbon, MD, of Bicêtre Hospital in Paris, France, told Pulmonology Advisor, “as PVR is a key marker of disease severity in PAH.”

There was also a substantial increase in the percentage of patients meeting ≥3 low-risk criteria from baseline to week 16 (23.9% to 68.2%, respectively).

The majority of patients (93.5%) experienced ≥1 adverse event (AE), with 28.3% (n=13) of patients reporting serious AEs. A total of 3 patients discontinued treatment due to AEs, and 3 patients died during the trial. Causes of mortality included cardiac arrest, heart failure, and multiorgan failure with sepsis. The most frequently occurring AEs included peripheral edema (n=13), headache (n=11), diarrhea (n=9), dyspnea (n=7), anemia (n=6), and asthenia (n=6).

Study limitations included the small sample size, short follow-up duration, and lack of a comparator group.

According to Dr Sitbon, all patients in the OPTIMA study have been enrolled in an open-label extension study, UMBRELLA (ClinicalTrials.gov Identifier: NCT03422328), to assess safety.

Dr Sitbon concluded that the data from the OPTIMA trial support the use of macitentan as part of a combination regimen in patients with PAH and add to the body of evidence supporting combination therapy as the standard of care.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Reference

Sitbon O, Canuet M, Picard F, et al. Initial treatment combination with macitentan and tadalafil in patients with pulmonary arterial hypertension: results from the OPTIMA study. Presented at: CHEST Annual Meeting 2019; October 19-23, 2019; New Orleans, LA. Abstract 870.