Researchers have discovered that, in patients with newly diagnosed pulmonary arterial hypertension (PAH), both initial double oral therapy and initial triple oral therapy successfully reduced pulmonary vascular resistance by the end of a 26-week observation period, according to a study published in the Journal of the American College of Cardiology.

“Pulmonary arterial hypertension (PAH) is a relentlessly advancing disease,” the authors of this study wrote in the introduction. To target the different pathways that contribute to its etiology, it has been common practice to prescribe combination therapy as part of PAH management. Newly diagnosed patients commonly receive either initial double oral therapy (macitentan and tadalafil) or initial triple oral therapy (macitentan, tadalafil, and selexipag). The authors of this study set out to discover if either type of treatment offered benefits over the other. 

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The researchers used data from the TRITON trial. A total of 291 patients were screened at 67 sites from March 7, 2016, until December 28, 2018. Of these, 247 patients received treatment; 124 received initial double oral therapy, while 123 received initial triple oral therapy. The primary endpoint for the measurement of the effects of both therapies on pulmonary vascular resistance was set at 26 weeks. 

The results indicated that both therapies demonstrated clinical benefits. Initial double therapy decreased pulmonary vascular resistance by 52% at 26 weeks, while initial triple therapy decreased pulmonary vascular resistance by 54%. This corresponded with a treatment effect of 0.96 (95% CI, 0.86-1.07; P =.42). In addition, both therapies were well tolerated. 

The authors concluded the article with a statement that invites future research: “Exploratory analyses suggested a signal for reduced risk for disease progression with initial triple versus initial double oral therapy, suggesting that incremental long-term benefit can be gained by oral targeting of 3 rather than 2 pathways.” 


Chin KM, Sitbon O, Doelberg M, et al. Three- versus two-drug therapy for patients with newly diagnosed pulmonary arterial hypertension. J Am Coll Cardiol. Published online September 27, 2021. doi:10.1016/j.jacc.2021.07.057