麻豆传媒

Earlier this year, empagliflozin (Jardiance) won FDA approval for a broader indication in heart failure across the spectrum of ejection fraction. As part of our review of the year's top stories, we follow up on what has happened since this approval.

Many heart failure patients started the year not being eligible for SGLT2 inhibitors. At the end of 2022, there is now one on the market with broad approval and there may soon be even more options.

This past February, the FDA gave empagliflozin, originally a diabetes drug, an expanded indication for reducing risk of cardiovascular death and hospitalization for heart failure patients across the spectrum of left ventricular ejection fraction (LVEF), including the mid-range (41-49%) and preserved (≥50%) LVEF categories previously left off its label.

Competing SGLT2 inhibitors are already arriving for heart failure across all LVEF. This month, regulators approved dapagliflozin (Farxiga) for heart failure across all ejection fraction categories.

The FDA is expected to follow suit with a similar approval stateside, based on dapagliflozin's major win in the DELIVER trial reported this summer. In DELIVER, the drug substantially cut the risk of combined cardiovascular death and worsening heart failure. Importantly, dapagliflozin proved that its benefits were consistent for patients above and below an LVEF of 60%. This contrasts with the EMPEROR-Preserved trial, in which empagliflozin users with LVEFs of 60% and higher showed an attenuated response in subgroup analysis.

Nevertheless, clinical benefits with SGLT2 inhibitors in heart failure are supported regardless of LVEF. Since the DELIVER trial's results were reported, dapagliflozin's benefits in heart failure have persisted in various secondary analyses of the trial, while EMPEROR-Preserved investigators published an analysis suggesting that empagliflozin's primary outcome benefit was statistically indistinguishable between people with .

U.S. guidelines were updated this year to endorse the class of SGLT2 inhibitors as a fourth pillar of therapy for symptomatic heart failure regardless of LVEF and diabetes status, a class IIa recommendation.

With dual SGLT1 and SGLT2 inhibitor added to the mix, the totality of the evidence suggests there is a class effect of SGLT2 inhibitors reducing unplanned hospitalizations or urgent visits for heart failure, said heart failure specialist Palak Shah, MD, MS, of Inova Heart and Vascular Institute in Falls Church, Virginia, and George Washington University in Washington, D.C.

When multiple choices appear in the market, the selection of which SGLT2 inhibitor to use is going to be driven predominantly by the cost of insurance copays and formulary decisions by pharmacy benefit managers in the U.S., Shah predicted during an interview. He acknowledged that there may also be some differences in kidney function criteria for eligibility of these drugs.

Pending an expanded approval, dapagliflozin remains restricted in heart failure to patients with reduced ejection fraction. The FDA's decision on an indication for sotagliflozin in heart failure without limitations on LVEF is expected to come by .

Ultimately, whether SGLT2 inhibitors do move the needle for patients remains to be seen. and other barriers have clinicians worrying that these medications won't be implemented widely enough in clinical practice.

This would be in line with the historical implementation issues of other guideline-directed medical therapies for heart failure. Factors such as titration requirements, high dosing intolerability, and a fragmented healthcare system are thought to contribute to their limited uptake around the world.

Since empagliflozin's broader FDA approval for heart failure in February, it has gained some momentum in clinical practice. Lilly reported in worldwide revenue from the SGLT2 inhibitor in the first quarter of this year, growing to and in the second and third quarters, respectively. It initially entered the market in 2014 as a drug to lower blood sugar in adults with type 2 diabetes.

There is hope that SGLT2 inhibitors will continue to gain acceptance in the real world, thanks to their ease of use for patients.

"The benefit of this class of medications is you do not necessarily need to think of what [LVEF] they have, you don't necessarily need to think of whether they are hemodynamically stable ... You don't necessarily need to worry about changes in electrolytes or kidney function," Shah said.

"This class of drugs is very well tolerated as well," he added, noting that the main side effect seems to be urinary tract infections.

Specialists are encouraged to work with other colleagues to spread the message about the benefits of SGLT2 inhibitors for heart failure -- yet the concept of the multidisciplinary team has not reached its full potential.

While the American College of Cardiology recently announced its new clinician education initiative, this will be limited who are already familiar with the SGLT2 inhibitor literature but need more education on how to use them safely in practice.

"Because it requires less nuance to prescribe and monitor, it is a therapeutic that should expand not just to cardiologists or other specialists, but other primary care physicians, hospitalists, family practitioners. That's provided they can get access to the drug," Shah said. "It always goes back to insurance, doesn't it?"

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