Empagliflozin Efficacious, Safe for Acute Heart Failure

Acute exacerbations of stable heart failure are commonplace. They are the most common cause of hospitalizations in persons over 65 years of age, lead to significant morbidity, and ultimately quicken mortality. Treatment goals are to relieve symptoms, restore oxygenation, improve organ perfusion and hemodynamics, limit cardiac and renal damage, prevent thromboembolism, and minimize length of stay. These are often difficult and require multiple different therapies.

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin and dapaglifozin are effective and relatively safe in heart failure. They reduce the risk of cardiovascular hospitalization and/or death for heart failure in patients with a reduced left ventricular ejection fraction (HFrEF).^{1, 2}

Empagliflozin has additionally shown benefit in patients with preserved left ventricular ejection fraction (HFpEF).³ Because SGLT2i improve ambulatory HFrEF and HFpEF, starting empagliflozin in the hospital may benefit patients with acute heart failure.

The EMPULSE trial enrolled 530 patients with primary diagnosis of acute de novo (first acute heart failure hospitalization) or decompensated heart failure independent of left ventricular ejection fraction. Patients were assigned to receive empagliflozin 10 mg or placebo daily.⁴ Patients received treatment in-hospital after they were clinically stable (therefore, the above treatment goals remain in place) at a median time of 3 days after admission.

Empagliflozin treatment resulted in clinical benefit measured by the composite of any-cause death, number of heart failure events, time to first heart failure event, or positive change in quality of life metric at 90 days (called a win ratio) of 1.36, 95% CI: 1.09-1.68. Clinical benefit was noted for both types of hospitalization criteria. Serious adverse events occurred in 32.3% of patients who received empagliflozin vs 43.6% of individuals in the placebo group.

The cardiology community welcomes the results of this study. These data will encourage clinicians to use SGLT2i earlier in the acute hospitalization independent of reason for admission, decrease the apathy of starting these agents after discharge, and result in more patients receiving these drugs chronically. This study does not, however, deal with the high cost of these agents, which is prohibitive for many patients and will lead discontinuation of these agents postdischarge.

References:

1. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413-1424. doi:10.1056/NEJMoa2022190
2. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapaglifozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303
3. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with preserved ejection fraction. N Engl J Med. 2021;385:1451-1461. doi:10.1056/NEJMoa2107038
4. Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 Inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28(3):568-574. doi:10.1038/s41591-021-01659-1