Key Points
• Source: ESC Heart Failure
• Conclusions/Relevance: “Our data indicate that empagliflozin might lead to an activation of both the Ang I–ACE–Ang II receptor axis and the Mas-axis pathway. Activation of the Ang I–ACE–Ang II receptor axis and the protective Mas-axis pathway after initiating treatment with empagliflozin was only seen in patients with ARB co-medication, in contrast to co-medication with ACEI.”
• The renin–angiotensin system (RAS) is necessary for fluid and sodium regulation. The classic angiotensin-converting enzyme–angiotensin II–angiotensin-1 receptor axis (Ang I–ACE–Ang II receptor axis) is predominantly angiotensin II (Ang-II) induced and supports vasoconstriction, whereas the angiotensin-converting-enzyme-2–angiotensin-(1-7)–Mas axis (Mas-axis) is controlled by the metabolites angiotensin-1-7 (Ang-(1-7)) and angtiotensin-1-5 (Ang-(1-5)) and offers cardioprotective effects
• In a trial called ELSI (Analysing the Effect of Empagliflozin on Reduction of Tissue Sodium Content in Patients With Chronic Heart Failure), German researchers previously studied the effect of empagliflozin on the tissue sodium content and the systemic hemodynamics in the context of CHF. In the current post hoc analysis, these researchers examined whether the SGLT-2 inhibitor empagliflozin modulates the RAS in 72 ELSI patients with CHF.
• Intriguingly, the activation of the Ang I–ACE–Ang II receptor axis and the Mas-axis pathway after initiating treatment with empagliflozin was demonstrated only among patients with ARB co-medication, whereas patients with ACEI co-medication not demonstrating empagliflozin-induced activation of either RAS pathway.
• The authors noted that large clinical trials such as DAPA HF, EMPEROR-Reduced, and EMPEROR Preserved did not involve a subgroup analysis by type of RAS blocking (ARB vs. ACEI co-medication). “In light of the experimental and clinical data of the protective effects of the Mas axis, our hypothesis is, based on the data above reported, that the beneficial effects of SGLT2 inhibitors might be more pronounced if patients with CHF were treated with ARB than with ACEIs. We urgently ask for sub-analyses of the mentioned prospective studies to verify our hypothesis,” the authors pleaded,” they wrote.
• Limitations of the current study include its small sample size, lack of causality, and difficulty in studying adaptations of RAS components during a treatment with RAS blockers