Cardiovascular Outcome Trials Offer New Hope for Heart Failure Patients – With or Without Diabetes

Sanjay Rajagopalan, MD
Cleveland, Ohio, USA

We all know that diabetes is one of the greatest risk factors for cardiovascular disease, particularly heart failure. Indeed, those with diabetes are two-and-a-half more times than those without to develop heart failure, while an estimated one in five people with diabetes also having heart failure.1 The worse their blood sugar control, the higher the risk of heart failure.2

This makes recent clinical trials on the benefits of the SGLT-2 inhibitors and GLP-1 receptor agonists so stunning. Spoiler alert: The verdict is far from over, but we are at a much better place in understanding the use of these agents in patients with or without diabetes who have heart failure than we were 6 months ago.

One study of importance is the EMPOROR-Reduced trial, which assessed the efficacy and safety of the SGLT-2 inhibitor empagliflozin in 3,370 patients with Class II-IV heart failure and an ejection fraction of ≤40%, half of whom had diabetes. Participants were randomized to placebo or empagliflozin (10 mg once daily) in addition to recommended treatments for heart failure for a median of 16 months.3

Patients receiving empagliflozin had a 24% lower risk of the combined primary endpoint of death, hospitalization for heart failure,  or an emergent/urgent heart failure visit requiring intravenous treatment (hazard ratio 0.76 [95% CI: 0.67-0.87], P<0.0001). Importantly, the investigators saw benefits just 12 days after randomization. 

The empagliflozin cohort also had a significantly reduced risk of heart failure hospitalization requiring intensive care, a vasopressor or positive inotropic drug, or mechanical or surgical intervention. They were also 20% to 40% more likely to experience an improvement in New York Heart Association (NYHA) functional class and 20% to 40% less likely to experience NYHA worsening. Keep in mind that these benefits accrued in patients who were already receiving state-of-the-art heart failure treatments, including beta blockers, aldosterone blockers, and an angiotensin receptor-neprilysin inhibitor.

This adds to the results of the DAPA-HF trial, which also demonstrated a powerful reduction in heart failure hospitalization and mortality in patients with and without diabetes receiving the SGLT-2 inhibitor dapagliflozin.4

The benefits of these agents are so profound that it is almost unethical not to start patients with heart failure on these drugs. 

Are there any barriers you face in prescribing these drugs? Do you start them in hospitalized patients given the rapid onset of effect? Please leave a comment below.

1  Nichols GA, Hillier TA, Erbey JR, Brown JB. Congestive Heart Failure in Type 2 Diabetes. Diabetes Care. 2001;24(9):1614. 10.2337/diacare.24.9.1614.
2  Iribarren C, Karter Andrew J, Go Alan S, et al. Glycemic Control and Heart Failure Among Adult Patients With Diabetes. Circulation. 2001;103(22):2668-2673. 10.1161/01.CIR.103.22.2668.
3 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.
4 McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008.



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