Introduction: The 2022 ESC/ERS Guidelines recommend initiating oral monotherapy in patients with pulmonary arterial hypertension (PAH) and cardiovascular comorbidities while initial combination therapy (combo) is recommended for PAH patients without comorbidity.

Aim: To compare efficacy of initial oral monotherapy and dual combo in PAH patients with at least 1 cardiovascular comorbidity.

Methods: All newly diagnosed PAH patients with at least 1 comorbidity (obesity, diabetes, hypertension, coronary heart disease) treated with either oral monotherapy or dual oral combo were analysed from the French PH Registry. Chi-2 test was used to compare distribution of risk strata between baseline and first reassessment. Propensity score was performed to match patients on age, pulmonary vascular resistance (PVR) and risk status at baseline.

Results: Among 1,066 patients analysed, 675 received initial monotherapy and 391 dual combo. Patients on monotherapy were older (67±11 vs. 65±13 years, p<0.01) and less severe (PVR 8±3 vs. 10±4 WU, p<0.01) than those on dual combo. After 5 months (IQR 4-8), of the 882 reassessed patients, 20% on monotherapy and 22% on dual combo achieved a low-risk status (p=0.01). After application of a propensity score, a low- and intermediate-low risk status was achieved in 16% and 32% on monotherapy, and in 23% and 38% on dual combo, respectively (p=0.02). Similar results were found in the subset of patients with at least 2 comorbidities (p=0.04).

Conclusion: The proportion of PAH patients with at least 1 cardiovascular comorbidity achieving a low-risk status at first follow up was greater in patients on initial dual combo than in patients on monotherapy.