ESC 2022: How to use gliflozins in heart failure? American guidelines now also consider the EMPEROR-Preserved study

Heart failure is still accompanied by grim data

More than 60 million people worldwide suffer from heart failure, and 50% of those with this disease die within 5 years. Additionally, it is the most common reason for hospitalization in patients older than 65 years. Readmission within 90 days occurs in 30% of patients, and approximately 30% of those hospitalized for heart failure die within 1 year. With these data, Dr. Javed Butler from the University of Mississippi in Jackson introduced the symposium.

In the treatment of HF, clear goals are set, namely the prevention of hospitalization due to this disease, improvement of survival and quality of life, prevention and alleviation of symptoms, and increase of functional capacity. "Despite current treatment options, hospitalization rates and mortality remain unacceptably high," the speaker stated, referring to a published paper by Oktay et al. [1], noting that the proportion of patients with preserved left ventricular ejection fraction (HFpEF – HF with preserved EF), who need hospitalization, has increased over time.

Evidence of empagliflozin efficacy in HF

Dr. Ileana Piña from Thomas Jefferson University in Philadelphia pointed out that more and more randomized controlled trials demonstrate that when it comes to cardiovascular (CV) outcomes and mortality in patients with HF, sodium-glucose co-transporter-2 inhibitors (SGLT2i, i.e., gliflozins) show a favorable profile. Several phase III studies comparing the effects of empagliflozin with placebo have shown that this medicine can significantly reduce the risk of CV death or HF hospitalization (HHF) across a wide range of LVEF values.

In the EMPEROR-Reduced study [2], which involved patients with HF with reduced LVEF (HFrEF – HF with reduced EF), the empagliflozin treatment arm saw a 25% reduction in relative risk (RRR) of CV death or first HHF (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.65–0.86; p < 0.001) and a 5.2% reduction in absolute risk (ARR) of these indicators.

In the EMPEROR-Preserved study [3], which focused on the same indicators in the population of patients with HFpEF, the RRR was 21% (HR 0.79; 95% CI 0.69–0.90; p < 0.001) and the ARR was 3.3%.

Therapy benefits regardless of ejection fraction

The consistency of favorable outcomes with empagliflozin compared to placebo across LVEF values was demonstrated by the pooled analysis EMPEROR-Pooled [4], the conclusions of which were published this year. CV and renal benefits of empagliflozin treatment remained consistent even in subgroup analyses considering age, gender, estimated glomerular filtration rate (eGFR), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) values. Safety data demonstrate good tolerance of empagliflozin and significant slowing of kidney function deterioration with its administration.

For clinical practice, according to the speaker, it is also very important that empagliflozin is taken once a day without the need for dose titration, can be combined with basic HF medication, and can be started during hospitalization after patient stabilization.

SGLT2i in HF treatment according to current guidelines

International guidelines support using SGLT2 inhibitors in patients with HFrEF as part of first-line treatment, as one of four fundamental pillars. European guidelines issued in 2021 [5] include these key changes for the treatment of HFrEF:

• SGLT2 inhibitors dapagliflozin and empagliflozin now have class 1 recommendations.
• The four key types of pharmacotherapy (SGLT2i, ACEi/ARNI, MRA, beta-blocker) should be introduced as quickly and safely as possible.
• Individualized management is essential for each patient.

This year's American guidelines (AHA/ACC/HFSA 2022 [6]) also consider the use of gliflozins in patients with heart failure with mid-range LVEF (HFmrEF) or HFpEF, as it can be beneficial for reducing hospitalizations and decreasing CV mortality even in this patient population. Professor Giuseppe M. C. Rosano from St. George's University Hospital in London pointed out that only these guidelines were issued after the conclusions of the EMPEROR-Preserved study were published.

The new class 1 recommendation for SGLT2 inhibitors according to the American guidelines applies to patients with HFrEF, regardless of the presence of type 2 diabetes. The four key types of HFrEF pharmacotherapy should be introduced simultaneously in low doses or sequentially according to clinical or other factors. In their introduction, it is not necessary to follow the sequence from published studies, and therapy initiation should not be delayed.

Eva Srbová
proLékaře.cz editorial team

Sources:
1. Oktay A. A., Rich J. D., Shah S. J. The emerging epidemic of heart failure with preserved ejection fraction. Curr Heart Fail Rep 2013; 10 (4): 401–410, doi: 10.1007/s11897-013-0155-7.
2. Packer M., Anker S. D., 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.
3. Anker S. D., Butler J., Filippatos G. et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021; 385: 1451–1461, doi: 10.1056/NEJMoa2107038.
4. Butler J., Packer M., Filippatos G. et al. Effect of empagliflozin in patients with heart failure across the spectrum of left ventricular ejection fraction. Eur J Heart Fail 2022; 43 (5): 416–426, doi: 10.1093/eurheartj/ehab798.
5. McDonagh T. A., Metra M., Adamo M. et al; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42 (36): 3599–3726, doi: 10.1093/eurheartj/ehab368.
6. Heidenreich P. A., Bozkurt B., Aguilar D. et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. J Am Coll Cardiol 2022; 79 (17): e263–e421, doi: 10.1016/j.jacc.2021.12.012.
7. Butler J. Welcome and introduction. SGLT2 inhibitors in practice (part 1): What is the state of heart failure treatment in 2022? ESC Congress, Barcelona, 2022 Aug 26.
8. Piña I. What is the evidence for SGLT2 inhibitors in HF? SGLT2 inhibitors in practice (part 1): what is the state of heart failure treatment in 2022? ESC Congress, Barcelona, 2022 Aug 26.
9. Rosano G. M. C. SGLT2 inhibitors for HF treatments in 2022: What do the guidelines tell us? SGLT2 inhibitors in practice (part 1): what is the state of heart failure treatment in 2022? ESC Congress, Barcelona, 2022 Aug 26.