The mechanisms for the benefits of Angiotensin Receptor Neprilysin inhibitor (ARNi) in heart failure patients with reduced ejection fraction (HFrEF) are likely beyond blood pressure (BP) reduction. Vascular function, a prognostic marker in HFrEF, improves with ARNi in animal models. Improvements in vascular function may contribute to benefits from ARNi in HFrEF; however, this has yet to be demonstrated in humans. The purpose of the study was to test the hypothesis that arterial stiffness and endothelial function would improve after 12 weeks of ARNi in HFrEF.
Methods:
HFrEF participants with NYHA class II-III were enrolled from local cardiology clinics and completed experimental visits at baseline and 12 weeks later: 13 participants were prescribed ARNi by their cardiologist [62±10 years, Men: 10, BMI: 30±5 kg/m
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, EF: 28±6 %; Non-ischemic cardiomyopathy (NICM): 8], 10 participants continued on conventional treatment [CON: 60±7 years, Men: 6, BMI: 31±6 kg/m
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, EF: 31±5 % and NICM: 4; all P=NS]. During each experimental visit, arterial stiffness was assessed via carotid-femoral pulse wave velocity (PWV; Sphygmocor PVx system) and endothelial function by brachial artery flow-mediated dilation (FMD) using standard techniques. Statistical analyses were performed using 2x2 repeated-measures ANOVA.
Results:
Baseline mean BP (MAP) was similar between ARNi (93±14 mmHg) and CON (85 ± 10 mmHg; P=0.13); MAP tended to decrease after 12 weeks of ARNi (88 ± 11 mmHg; P=0.08) but not CON (90 ± 17 mmHg; P=0.14) (ANOVA interaction P=0.03). PWV tended to be higher at baseline in ARNi (8.8 ± 2.5 m/s) compared to CON (7.0 ± 2.5 m/s; P=0.09); PWV decreased after 12 weeks of ARNi (7.0 ± 1.7 m/s; P<0.01) and was unchanged in CON (7.4 ± 2.4 m/s; P=0.33) (ANOVA interaction P<0.01). When controlling for MAP, the effect of ARNi on PWV remained (P<0.01). At baseline, FMD was similar between ARNi (2.81 ± 2.05%) and CON (4.75 ± 3.75%; P=0.13); however, FMD increased after 12 weeks of ARNi (5.73 ± 1.87%; P<0.001) but not in CON (5.37 ± 3.38%; P=0.33) (ANOVA time P<0.001, interaction P=0.01).
Conclusion:
ARNi improves arterial stiffness and endothelial function in HFrEF. Understanding the mechanisms of ARNi in HFrEF is crucial as it may pave the way for better interventions in other cardiovascular diseases.
Estimated 5-Year Number Needed to Treat to Prevent Cardiovascular Death or Heart Failure Hospitalization With Angiotensin Receptor-Neprilysin Inhibition vs Standard Therapy for Patients With Heart Failure With Reduced Ejection Fraction
