Risk Reduction and Hemodynamics with Initial Combination Therapy in Pulmonary Arterial Hypertension

Rationale: An initial oral combination of drugs is being recommended in pulmonary arterial hypertension (PAH), but the effects of this approach on risk reduction and pulmonary vascular resistance (PVR) are not known. Objective: To test the hypothesis that a low-risk status would be determined by the reduction of PVR in PAH patients treated upfront with a combination of oral drugs. Methods. The study enrolled 181 treatment-naive PAH patients (81 % idiopathic) with a follow-up right heart catheterization at 6 months (IQR 144-363 days) after initial combination of endothelin receptor antagonist + phosphodiesterase-5 inhibitor drugs and clinical evaluation and risk assessments by European guidelines and REVEAL scores. Results. Initial combination therapy improved functional class and 6-min walk distance, and decreased PVR by an average of 35 % (median - 40 %). A third of the patients had a decrease in PVR < 25 %. This poor hemodynamic response was independently predicted by age, male sex, pulmonary artery pressure and cardiac index, and at echocardiography a right/left ventricular surface area ratio >1 associated with low tricuspid annular plane systolic excursion (TAPSE) < 18 mm. A low risk status at 6 months was achieved or maintained in only 34.8% (REVEAL score) to 43.1% (European score) of the patients. Adding criteria of poor hemodynamic response improved prediction of a low risk status. Conclusion. A majority of PAH patients still insufficiently improved after 6 months of initial combinations of oral drugs is identifiable at initial evaluation by hemodynamic response criteria added to risk scores.