Efficacy and tolerability of SGLT2 Inhibitors in patients with pulmonary arterial hypertension and cardiovascular comorbidities

Objectives: During the last years the clinical phenotype of pulmonary hypertension (PH) has changed, in such a way that increasingly older patients with cardiovascular comorbidities are diagnosed. The Sodium-glucose Cotransporter-2 inhibitors (SGLT2i) are used for the therapy of symptomatic chronic heart failure. The objective of this study consisted in analyzing the effects of the therapy with SGLT2i in patients with pulmonary arterial hypertension (PAH) and left heart failure with preserved ejection fraction (HFpEF) as cardiovascular comorbidity.

Methods: PAH patients with concomitant HFpEF under stable PH therapy receiving SGLT2i were included in this retrospective cohort study. The primary endpoint comprised the change in right atrial (RA) area and right ventricular (RV) function on therapy with SGLT2i. Clinical, echocardiographic and clinical laboratory parameters were analyzed, as well as exercise capacity measured by the 6-minutes walking distance (6MWD).

Results: In total 252 patients received a therapy with SGLT2i. After exclusion of the patients without follow-up examinations, 198 patients (74±28 years, 61 % female; 84% Functional Class ≥III) were evaluated. Additional treatment with SGLT2i led to a significant improvement of the primary endpoint with a reduction in RA area -1.9±4.5 cm² (p<0,0001) and improvement in RV function (improvement n=54 vs. worsening n=5; p<0,001) during the follow-up of 6.7±3.3 months. Furthermore, there was a significant reduction in RV area -1.7±4.8 cm², in left atrial diameter -2.2±4.4 mm and systolic pulmonary arterial pressure of -9.3±16.1 mmHg (all p<0.0001). 6MWD improved by 51.6±58.5 meters (p=0.0001). Five patients discontinued the medication due to side effects.

Conclusion: The additional SGLT2i treatment led to a significant improvement in RA area size and RV function, as well as in further clinical parameters. Therapy with SGLT2i was well-tolerated and efficacious, thus it could present a good addition to targeted PAH therapy. Further studies in this field are necessary to confirm these results.