Initial triple therapy associated with improved long-term survival in high-risk PAH

Initial triple combination therapy was associated with better survival among high-risk patients with severe pulmonary arterial hypertension at diagnosis, especially among younger high-risk patients, according to a new study.

“This study supports the utility of multidimensional risk stratification to choose the most appropriate initial treatment strategy for newly diagnosed PAH patients,” Athénaïs Boucly, MD, from the University of Paris-Saclay School of Medicine and the department of respiratory and intensive care medicine at Bicêtre, Le Kremlin-Bicêtre, and Marie Lannelongue Hospital, Le Plessis-Robinson, France, and colleagues wrote in the American Journal of Respiratory and Critical Care Medicine.

The retrospective analysis included 1,611 patients (mean age, 60 years; 56% women) with idiopathic, heritable or anorexigen-induced PAH who were enrolled in the French Registry from 2006 to 2018. Researchers assessed survival based on initial strategy: monotherapy (n = 984), dual combination (n = 551) or triple combination (n = 76), which included two oral medications and parenteral prostacyclin therapy.

Those in the triple combination therapy group were younger and had fewer comorbidities, but higher mortality risk.

There was a higher proportion of patients with zero or one low-risk criteria at baseline (91%) among patients initiated on triple combination therapy compared with monotherapy (57%) or dual therapy (72%). At a median follow-up of 5 months, 78% of patients in the triple combination therapy group had three or four low-risk criteria compared with 36% of patients in the monotherapy group and 47% of patients in the dual therapy group.

Over a median follow-up of 32 months, 32% of patients died, and 4% patients underwent lung transplantation. In the monotherapy group, 35% of patients died and 3% underwent lung transplantation during a median follow-up of 35 months. In the dual therapy group, 28% died and 5% underwent lung transplantation during a median follow-up of 28 months. In the triple therapy group, 9% died and 14% underwent lung transplantation during a median follow-up of 39 months.

At 5 years, survival was higher among patients in the triple therapy group compared with those in the dual or monotherapy groups (91% vs. 61%; P < .001). Researchers also observed higher transplant-free survival at 5 years among patients in the triple therapy group, at 75% compared with 58% in the monotherapy group and 56% in the dual therapy group.

The researchers also assessed survival based on patient disposition according to the European Society of Cardiology/European Respiratory Society risk status at baseline. Among 243 high-risk patients at baseline, survival was higher among those who received initial triple therapy compared with monotherapy or dual therapy (P < .001). However, there were no differences between monotherapy and dual therapy. Among patients at intermediate risk (n = 1,134), survival was shown to improve as number of therapies increased (P < .001).

In addition, triple combination therapy was independently associated with lower mortality risks (HR = 0.29; 95% CI, 0.11-0.8; P = .017). In patients with intermediate risk, initial therapy yielded a survival benefit compared with dual therapy and monotherapy (P < .001), and dual therapy had a greater survival benefit compared with monotherapy only (P = .025).

“While randomized trials are needed to conclusively evaluate the efficacy of triple therapy, these findings provide new evidence to support the PAH treatment algorithm presented in the European Society of Cardiology/European Respiratory Society guidelines and the 6th World Symposium on Pulmonary Hypertension,” the researchers wrote.