SGLT2 inhibitors improve risk in heart failure

Recent studies on heart failure treatment showed that SGLT2 inhibitors reduced the risk of cardiovascular death or even hospitalization in heart failure, with reduced ejection fraction compared to placebo.

Cardio- and nephroprotective effects are reconfirmed

Recent studies on the treatment of heart failure at this year's ESC 2020 showed that SGLT2 inhibitors reduced the risk of cardiovascular death or even hospitalization in heart failure with reduced ejection fraction compared to placebo.

At this year's ESC Digital Congress, recent studies on the treatment of heart failure showed that SGLT2 inhibitors, such as empagliflozin, reduced the risk of cardiovascular death or even hospitalization in heart failure with a lower ejection fraction compared to placebo [1-3]. These effects occurred regardless of whether diabetes mellitus was present or not.

SGLT2 inhibitors (sodium-glucose co-transporter 2 inhibitors) were originally approved as antidiabetics. However, numerous studies have shown an interesting "side effect" of this group of drugs: SGLT2 inhibitors appear to be both cardioprotective and nephroprotective.

Cardioprotection through SGLT2 inhibitors

For example, an important study on the efficacy of SGLT2 inhibitors in heart failure used the SGLT2 inhibitor dapagliflozin, which already reduced the risk of cardiovascular death or hospitalization in heart failure with reduced ejection fraction, regardless of the patient's diabetes status.

This study primarily enrolled patients (n = 4,744) with mild to moderate left ventricular systolic dysfunction (LVSD) and increased natriuretic peptide levels. The results also served as a starting point for further study to investigate the effects of SGLT2 inhibitors in patients with heart failure and significantly reduced ejection fraction.

Data on cardioprotection by SGLT2 inhibitors confirmed

This current study, presented by Dr. Milton Packer (Baylor University Medical Center, USA) at the virtual ESC 2020, used empagliflozin in 3,730 patients with mild, moderate, or severe chronic heart failure (Class II, III or IV) and reduced ejection fraction. Only half of the patients included suffered from concomitant diabetes mellitus, the other half were diabetes-free. The randomization was carried out in two groups: 1,863 patients received empagliflozin (10 mg once daily), 1,867 received a placebo.

The trials concentrated on three main study endpoints:

The primary endpoint was a composite endpoint of cardiovascular death and hospitalization after heart failure.
The first secondary endpoint included all hospitalizations after initial and repeated heart failure.
The second secondary endpoint included a decrease in glomerular filtration rate over time.

As a result of the study, the primary endpoint was met and the risk of cardiovascular death or hospitalization was reduced by 25% compared to placebo. Overall, the risk for total hospitalization was also reduced by 30% in the first secondary endpoint.

Nephroprotection by empagliflozin

The decrease in glomerular filtration rate in the second secondary endpoint was also significantly slowed within 16 months compared to placebo: -4.2 ml/min/1.73 m2 for placebo versus -0.9 ml/min/1.73 m2 for empagliflozin.

The annual rate of decrease in the estimated glomerular filtration rate was thus significantly slower in the empagliflozin group than in the placebo group. In addition, patients treated with empagliflozin had a lower risk of severe renal events.

What do these data mean for medical practice?

Both trials showed that SGLT2 inhibitors have significant clinical benefits for cardio- and nephroprotection in patients with heart failure and are also well tolerated. According to Dr. Packer, the results of the dapagliflozin and empagliflozin trials provided convincing evidence that SGLT2 inhibitors should be added to the recommended treatments for heart failure patients with and without diabetes - but with a reduced ejection fraction - in the future.

References:
1. Packer M. Empagliflozine in heart failure with a reduced ejection fraction, with and without diabetes. Hot Line 1, ESC Congress 2020, 29th Aug
2. Packer M, et al., New Engl J Med 2020; DOI: 10.1056/NEJMoa2022190
3. Zannad F et al, The Lancet 2020; DOI: 10.1016/S0140-6736(20)31824-9

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