The combination of sacubitril/valsartan (Entresto®) plus dapagliflozin (Farxiga®) could alleviate pulmonary arterial hypertension (PAH) by improving patients’ left heart function, according to a new study published in Perfusion.

“Our results showed that sacubitril/valsartan combined with dapagliflozin effectively improved vascular endothelial functions in patients with PAH due to left heart disease, indicating synergy between the two drugs,” the authors said.

Both the treatment and control groups showed improved hemodynamics after 6 months of treatment, including reduced left ventricular end systolic diameter, left ventricular end diastolic diameter, mean pulmonary artery pressure and pulmonary artery systolic pressure, and longer 6-minute walk test distances. However, improvements were greater in patients treated with sacubitril/valsartan plus dapagliflozin.


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Moreover, patients in the treatment group had more prominent changes in vascular endothelial function, heart failure, and inflammatory markers after 6 months of treatment. These included decreased plasma endothelin, plasma N-terminal pro-brain natriuretic peptide, serum C-reactive protein, interleukin 6, and tumor necrosis factor α. They also showed increased plasma levels of the vasodilator nitric oxide.

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The incidence of adverse drug reactions was similar between the treatment and control groups and included hypoglycemia, hypotension, urinary tract infection, genital tract infection, renal injury, and vascular edema.

The randomized controlled trial enrolled 120 patients diagnosed with PAH caused by left heart disease. Patients in the treatment arm received a combination of sacubitril/valsartan plus dapagliflozin, while patients in the control arm were given sacubitril/valsartan. In addition, both groups received baseline treatment to control primary left heart disease.

Dapagliflozin is a blood glucose-lowering agent that acts by reducing glucose resorption in the glomeruli. Because of this, it is not expected to affect blood glucose levels during long-term use.

Reference

Ge T, Yang Y, Zhao Y. A study of the efficacy of sacubitril/valsartan plus dapagliflozin combination treatment in pulmonary arterial hypertension due to left heart disease. Perfusion. Published online September 29, 2022. doi:10.1177/02676591221127924