SGLT2 inhibitors in HFpEF: good for heart and kidney
It has not yet been conclusively clarified why SGLT2 inhibitors are associated with good outcomes in heart failure with pEF. The most relevant mechanisms of action were presented at the DGK 2023.
Key takeaways about SGLT2 inhibitors:
- SGLT2 inhibitors lead to marked glycosuria and thus promote osmotic diuresis.
- By reducing glomerular pressure, deterioration of renal function is slowed.
- Therapy with SGLT2 inhibitors resulted in a decrease in epicardial and subcutaneous adipose tissue.
- In patients with HFpEF, diastolic wall stress is reduced.
HFpEF: different patients, different therapy needs
Unlike heart failure with reduced ejection fraction, it is mainly older women who suffer from HFpEF. There is often comorbidity with atrial fibrillation and hypertension - and, as with the other types, association with chronic kidney disease. It is estimated that about half of all people with heart failure have at least reduced kidney function. Within five years, about 30 % of those with the disease die, while only about 12 % reach the dialysis stage. This makes it all the more important to find therapy options that work on both kidney function and the heart.
SGLT2 inhibitors are not only useful for diabetics
The primary effect of SGLT2 inhibitors is glucose filtration, which leads to glucosuria. This works not only for diabetics, but also for non-diabetics: here, one assumes a sugar excretion of about 60g per day. The associated osmotic diuresis is a desired effect in heart failure. However, compared to classic loop diuretics, the SGLT2 inhibitors do not reduce the intravascular volume, but only the interstitial volume.
Kidney protection is an important factor
Especially for multimorbid patients, such as those with HFpEF, an organ-protective effect is important. SGLT2 inhibitors not only have a diuretic effect, but also reduce the glomerular pressure in the kidney tissue. This occurs through a constriction of the vas afferens (a.k.a. Afferent glomerular arteriole). This mechanism reduces albuminuria and slows down the deterioration of renal function.
Positive effect also on the heart and fatty tissue
Studies have shown that the effect of SGLT2 inhibitors is not limited to the kidneys. Rather, they also have an influence on fatty tissue. While the drugs mainly affect visceral fat in diabetics, they reduced epicardial and subcutaneous fat tissue in people with heart failure.
The drugs also have a positive effect on cardiac activity. They have been shown to improve cardiomyocyte stiffness and titin phosphorylation in patients with HFpEF. Also a reduced diastolic wall tension as well as a reduced afterload and better energy supply of the myocardium by ketone bodies, amino acids and free fatty acids are positive effects of the SGLT2 inhibitors that apply specifically to HFpEF patients.
Conclusion for medical practice: improved outcomes for HFpEF patients
SGLT2 inhibitors are associated with improved outcomes for HFpEF patients. Why this is so is not yet conclusively understood. However, recent studies and clinical data show a decrease in cardiovascular and renal events with therapy with the drugs.
von Haehling, Stephan, Prof. Dr. Dr., Göttingen University Hospital, Heart Centre, Clinic for Cardiology and Pneumology, Germany (In German: Universitätsmedizin Göttingen Herzzentrum, Klinik für Kardiologie und Pneumologie Göttingen, Deutschland), Session: Role of SGLT2 inhibitors in heart failure therapy - effect on heart and kidney in HFpEF (Original German title: Rolle der SGLT2-Inhibitoren bei der Therapie der Herzinsuffizienz – Wirkung auf Herz und Niere bei HFpEF). 89. Annual Conference of the German Society for Cardiology (German acronym: DGK), Mannheim, Germany. 13 April 2023