Dare to Prescribe SGLT 2 Inhibitors in Acute Heart Failure?

CME INDIA Presentation by Dr. N.K. Singh, MD, FICP, Director, Diabetes and Heart Research Centre, Dhanbad, Jharkhand, India. Editor, www.cmeindia.in.

Adding a new patient profile in whom we can start empagliflozin in hospital. Starting SGLT2 inhibitors as soon as in the hospital, shown to be safe in EMPULSE.

“This is the first time we have really seen this type of medication work so effectively and safely in patients who were hospitalized for acute heart failure, regardless of heart failure history or diabetes status. These results may lead to earlier and more frequent treatment with empagliflozin, which may improve the lives of more people with heart failure.” – Adriaan Voors, MD, PhD (Lead Author, EMPLUSE Trial).

Quick Take Away

• EMPLUSE trial results will impact the practice of clinicians worldwide.
• Acute heart failure is the number one cause of hospitalization in individuals over the age of 65.
• EMPULSE trial got published in Nature Medicine on 28th Feb 2022 but findings were presented at AHA meeting on November 14th, 2021.
• EMPULSE alone will not be enough to change the US Food and Drug Administration-approved indications for use.
• It strongly opens a new window for Empagliflozin in patients with acute heart failure as 36% more likely to “experience a clinical benefit” over the next 90 days compared with patients taking a placebo.
• Even in chronic heart failure there is a little reluctance in starting a chronic heart failure. In chronic heart failure, we have now guideline-oriented indication to start SGLT2 inhibitors. Trials like EMPEROR-Preserved, EMPEROR-reduced, DAPA-HF, changed the whole landscape in CHF.
• If you compare with previous SOLOIST trial was a more semi acute heart failure trial, partly in hospital, partly post discharge, but only in patients with diabetes. Only 530 patients, so we will need larger trials to substantiate it.
• Now there is a very vital piece of evidence for consideration of empagliflozin in Acute Heart Failure in patients hospitalized.
• At present there is no FDA green signal.

What Larger Trials are going on in Acute Heart Failure?

1. DICTATE-AHF and
2. DAPA ACT HF-TIMI 68 trials, both with dapagliflozin

This Study is being considered a land mark

Unique Inclusion Criteria

• First presentation of heart failure was actually hospitalisation.
• Also done in patients with chronic heart failure, who’d be compensated.
• It was with patients both with and without diabetes.
•  It was irrespective of whether they had a left ventricular ejection fraction below or above 40 or 50.
• The only thing is that they needed to be stabilised in a way that they didn’t have signs of hypotension.
• They had no active phase of dilators in the last six hours.
• They had no change in the loop diuretic in the last six hours and no IV inotropic drugs in the last 24 hours.
• Needed to have elevated natriuretic peptides.

Will not Empagliflozin induce hemodynamic instability in Acute Heart failure?

• This is the most important fear in physician’s mind.
• There are concerns to give a drug in a vulnerable phase.
• But what was observed is exciting. This drug actually could even provide more diarrhesis on top of loop diuretics.
• It could have other hemodynamic or metabolic improvements related to better outcomes.

Principal Findings: Worth pondering

• The primary analysis was assessed by a stratified win ratio, defined as a composite of death, number of heart failure events, time to first heart failure event, and change in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) from baseline to 90 days.
• Clinical benefit occurred at a rate of 53.9% in the empagliflozin group compared with 39.7% in the placebo group (p = 0.0054). There was no evidence for treatment interaction among various tested subgroups.
• So, researchers found, from the primary endpoint that in 53.9 of the cases, empagliflozin was the winner in 39.7%.
• In 6% there was a tie.
• We can see that the win ratio was 1.36 with a P-value of 0.0054, which means that patients on empagliflozin were 36% more likely to obtain a clinical benefit from empagliflozin.
• In the placebo group and only one in the empagliflozin group, (self-reported acute renal failure), occurred in 7% in the empagliflozin group versus 12% in the placebo group.
• We know that with SGLT2 Inhibitors there is a slight drop in the eGFR, which recovers after 30 days or 90 days, and it gets back to normal again.
• Overall, the safety profile was found excellent.

Secondary outcomes:

CME INDIA Learning Points

• Combining data from the pivotal EMPHASIS-HF, PARADIGM-HF, and DAPA-HF (of an MRA, ARNI, and SGLT2 inhibitor, respectively),has suggested that the aggregate treatment effects of all three agents on top of long-standing, conventional care could extend survival up to 6 years, while also reducing hospital admissions.
• An SGLT2 inhibitor works just as well in terms of relative risk reduction for mortality and hospitalization whether the patient is on an ARNI or not on an ARNI, whether the all four drugs, stat, with a shift away from getting one agent to full strength before adding another.
• Even if patients are on a beta-blocker or not on a beta-blocker, adding SGLT2 inhibitors brings unique benefit.
• In 2022, emerging consensus tells that all four drugs be initiated on day one of a HF hospitalization, at low doses for the ARNI, beta-blocker, and MRA (the SGLT2 inhibitor being a standard dose).
• In EMPULSE trial, among patients with acute decompensated heart failure, empagliflozin versus placebo was associated with significant clinical benefit at 90 days.
• Empagliflozin versus placebo was also associated with fewer deaths, improvement in quality of life, and greater reduction in body weight.

CME INDIA Tail Piece

The Need for Speed

“True – unbelievable. It appears, these drugs shall continue to amaze us for decades. SGLT2i/ Empa in acute heart failure – EMPULSE trial result now published – passed the acid test.” – Dr. A.K. Singh, DM, Endo., Kolkata.

“It doesn’t matter how many trials we do, it doesn’t matter how many guidelines people write, [or] how many presentations we give at national or international meetings: physicians are not prescribing these drugs.” – Milton Packer.

“There’s a whole generation of physicians saying: what’s the point in getting those drugs added as fast as possible?” – Nathan Mewton.

References:

1. Presented by Dr. Adriaan A. Voors at the American Heart Association Virtual Annual Scientific Sessions (AHA 2021), November 14, 2021
2. Voors, A.A., Angermann, C.E., Teerlink, J.R. et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med (2022). https://doi.org/10.1038/s41591-021-01659-1
3. https://www.tctmd.com/news/avoiding-af-triggers-doesnt-improve-quality-life-i-stop-afib

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