ESC Updates Add SGLT2 Inhibitors Across HF Spectrum, New Diabetes Score, First Guide in Cardiomyopathies

What do you do when your 5-year guidelines update in heart failure (HF) is outdated within hours of release?

That’s the challenge the European Society of Cardiology (ESC) faced 2 years ago, when its scheduled review of clinical guidelines in HF, released during the group’s virtual Congress, was overtaken within hours by landmark results from the EMPEROR-Preserved trial. That study found significant benefits from the sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (Jardiance, Boehringer Ingelheim and Eli Lilly) for patients with HF with preserved ejection fraction (HFpEF).

As John McMurray, MD, program chair of ESC 2023, reminded reporters gathered in Amsterdam ahead of the Congress that opens today, the commitment was made on the spot to offer an interim update this year.

And so, today ESC is releasing its interim guidelines update in HF, along with updates for the following: (1) recommendations to reduce cardiovascular (CV) risk in patients with diabetes, (2) recommendations on treatment of acute coronary syndromes, (3) recommendations on treatment of endocarditis, and (4) the first international guidelines on the treatment of heart muscle diseases, or cardiomyopathies. All are published today in European Heart Journal.^1-5

Interim HF update. Heart failure is the focus of this year’s ESC Congress, and the interim update reflects a revolution in therapeutic approaches—and even in definitions—for HF in recent years. Before 2021, there were no approved therapies for HFpEF, which had often been defined as left ventricle ejection fraction (LVEF) of 45% or above. The 2021 update reflected use of SGLT2 inhibitors in HF with reduced ejection fraction (LVEF of 40% or lower), but in addition to EMPEROR-Preserved, other important trials have been published involving SGLT2 inhibitors empagliflozin and dapagliflozin (Farxiga, AstraZeneca), among other therapies.

“In 2021, the ESC published guidelines for the diagnosis and treatment of acute and chronic heart failure,” said Marco Metra of the University of Brescia, Italy, heart failure guidelines task force chair, in a statement. “Since then, more than 10 randomized controlled trials have been released that should change patient management ahead of the next scheduled full guideline, necessitating a focused update.”

The field now recognizes mildly reduced HF (HFmrEF), with LVEF between 41% and 49%, as a separate phenotype. The guidelines now recommend use of empagliflozin or dapagliflozin for patients with HFmrEF and HFpEF to reduce the risk of HF hospitalization or CV death.

Other recommendations include:

• Starting patients on HF therapy before discharge for acute HF, and rapidly increasing dose levels with careful monitoring to avoid repeat hospitalizations
• In patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), the update recommends use of SGLT2 inhibitors to reduce the risk of HF hospitalization or CV death; finerenone is recommended in this patient population to reduce the risk of HF hospitalization
• Intravenous (IV) iron is recommended for symptomatic patients with HFrEF and HFmrEF and iron deficiency to improve quality of life; IV iron supplementation with ferric carboxymaltose or ferric derisomaltose should be considered in symptomatic patients with these HF ranges and iron deficiency to reduce HF hospitalization risk.

Diabetes and cardiovascular disease. ESC reports that mortality rates are 50% to 90% higher for patients with T2D and HF than among those with HF alone. With this in mind, the Congress now recommends systematic screening for all patients with diabetes and comorbid CVD.

The guidelines update introduces a new scoring system, called SCORE2-Diabetes, to estimate the 10-year risk of fatal and nonfatal myocardial infarction and stroke in patients with T2D. The guidelines also re-emphasize the need for healthy eating and exercise along with weight control, calling weight reduction the cornerstone of treatment for those who are obese, and recommending 150 minutes of moderate exercise per week, noting, “every step counts.”

Screening is a big focus of this update, with recommendations for at least annual screening for CKD among patients with T2D, and an inaugural recommendation to screen these patients for atrial fibrillation at age 65.

In light of recent trials, the guidelines recommend SGLT2 inhibitors and/or glucagon-like peptide-1 receptor agonists to reduce the risk of heart attack and stroke in all patients with diabetes and CVD.

"And, of course, this is on top of standard of care," said diabetes and CVD task force co-chair Nikolaus Marx, MD, of Aachen University, Germany, during Friday's session. If the patients needs additional therapy for glycemic control, he said, the guidelines outline options from other drug classes that can be considered.

Cardiomyopathies. Described as “the first international guideline document to include all cardiomyopathy subtypes,” the ESC recommendations include heart muscle conditions beyond hypertrophic cardiomyopathy. The guidelines note both the genetic nature of these conditions and the challenge of diagnosis and management, as some people may experience no symptoms at all while others may experience fatigue or shortness of breath.

In a statement, the ESC said, “Diagnosis starts with a description of how the heart looks and behaves—is it thickened, dilated or scarred, and is the pumping function abnormal?” From there, the analysis evaluates heart rhythm abnormalities, family history, and genetic testing to settle on a diagnosis. In some cases, the guidelines note, a patient may be advised to curtail competitive sports or weigh whether to have children. Some patients may need a heart transplant, or physicians may recommend an implantable cardioverter defibrillator to prevent sudden death.

ESC recommends a multidisciplinary approach to care and appropriate preparation as patients transition from pediatric to adult cardiomyopathy services. Care for those with cardiomyopathies requires a team approach, the guidelines state, including cardiologists, geneticists, genetic counselors, pathologists, and other specialties, as well as good coordination between primary and other levels of care.

Acute coronary syndromes. In addition to updated recommendations on use of anticoagulant and antiplatelet therapy, the ESC guideline contains a new section it sees as a sign of the times: recommendations on the management of ACS in patients with cancer. These patients are at increased risk of ACS due to common risk factors such as smoking, type of cancer, and the effects of treatment with chemotherapy and radiotherapy. As the number of cancer survivors increases, so does the likelihood that more patients will be affected by cardiotoxic effects of treatment. ESC’s guideline reminds users that CVD remains the leading cause of death, and those with cancer are not spared.

The guidelines note that those under active treatment for cancer face increased bleeding risk, which must be weighed in making treatment decisions. Recommendations include angiography and insertion of a stent if needed if patients are expected to live at least 6 months. Temporary interruption of cancer therapies should occur of they are suspected of contributing to ACS.

Endocarditis. The update discusses specific cardiac conditions, such as valvular heart disease and congenital abnormalities, or those requiring a pacemaker, that could lead to rare but potentially deadly infections of the heart’s inner lining and valves. This update discusses the need for good dental and skin hygiene to help prevent infection, how to evaluate an individual patient’s risk level, and when prophylactic antibiotics should be used to prevent infection, especially ahead of an event such as a dental procedure.

“One of the worst complications of endocarditis is stroke. Decisions about the timing of surgery in patients who have suffered a stroke must balance the risk of neurological deterioration during the procedure against that of delaying surgical therapy,” the ESC said in a statement.

References

1. McDonagh TA, Metra M, Adamo M, et al. 2023 focused update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. Published August 25, 2023. doi:10.1093/eurheartj/ehad195
2. Marx N, Federici M, Schutt K, et al. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. Published August 25, 2023. doi:10.1093/eurheartj/ehad192
3. Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC guidelines for the management of cardiomyopathies. Eur Heart J. Published August 25, 2023. doi:10.1093/eurheartj/ehad194
4. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J. Published August 25, 2023. doi:10.1093/eurheartj/ehad191
5. Delgado V, Marsan NA, de Waha S, et al. 2023 ESC guidelines for the management of endocarditis. Eur Heart J. Published August 25, 2023. doi:10.1093/eurheartj/ehad193