ESC Focused Update on HF Synthesizes New Trial Data for Practical Use

More than a dozen new RCTs dedicated to acute and chronic heart failure (HF) have come out over the course of just the past few years since the 2021 European Society of Cardiology (ESC) Guidelines on the topic—the time was ripe for a focused update, the writing committee said last week.

“We felt we had to do an update because heart failure is obviously a rapidly changing field,” said guideline chair Theresa A. McDonagh, MD (King’s College Hospital, London, England), who presented the latest recommendations in a Hot Line session at the ESC Congress 2023 in Amsterdam, the Netherlands.

The update, which featured advice for treatment and diagnosis, was simultaneously published in the European Heart Journal.

Among the influential trials up for consideration across the spectrum of acute HF, chronic HF, and comorbidities were ADVOR, COACH, DELIVER, EMPEROR-Preserved, EMPA-KIDNEY, IRONMAN, REVIVED-BCIS-2, and STRONG-HF.

“Obviously, the main new evidence we had to consider for chronic heart failure was the SGLT2 inhibitors dapagliflozin and empagliflozin,” McDonagh said, “because both the EMPEROR-Preserved trial and the DELIVER trial met their primary endpoints with reduction in cardiovascular deaths or hospitalizations for heart failure by similar degree.”

Based on that evidence, the guidelines now give both SGLT2 inhibitors a class IA indication for management of patients who have symptomatic HF with mildly reduced ejection fraction (HFmrEF) and those who have heart failure with preserved ejection (HFpEF).

In acute HF, the main change is the level of evidence for predischarge and early postdischarge follow-up of patients with a HF hospitalization. This upgrade is based on results of the STRONG-HF study, which showed a reduction in the rate of all-cause death or HF readmission with rapid uptitration to full doses of renin-angiotensin-aldosterone-system (RAAS) inhibitors, beta-blockers, and mineralocorticoid receptor antagonists (MRAs) compared with usual care. The trial was stopped early due to a greater-than-expected benefit of the high-intensity management strategy.

“We added the recommendation, level of evidence B, class I, to have the initiation and the rapid uptitration of evidence-based treatment before discharge [then] doing frequent and careful follow-up visits in the first 6 weeks after the heart failure hospitalization,” said McDonagh’s co-chair, Marco Metra, MD (University of Brescia, Italy).

To TCTMD, Metra noted that it may be challenging to implement the frequency of follow-up visits in the real world as was done in STRONG-HF, with approximately four postdischarge visits in 6 weeks.

“Accordingly, we kept our recommendation more generic, stating that evidence-based treatment had to be initiated and titrated before discharge and during ‘frequent and careful follow-up visits in the following 6 weeks,’” he said in an email.

Addressing Comorbidities, Pondering Iron

The committee also reviewed the EMPA-KIDNEY data, DAPA-CKD, and a meta-analysis on the effects of SGLT2 inhibitors on kidney outcomes. They give a class IA recommendation for dapagliflozin or empagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) to reduce the risk of HF hospitalization or CV death.

The CKD recommendation change applies to the use of finerenone, which is supported by data from FIDELIO-DKD, FIGARO-DKD, and a pooled analysis showing reductions for the MRA versus placebo on composite CV and HF hospitalization outcomes. On the basis of these data, finerenone also gets a class IA recommendation in patients with type 2 diabetes and CKD to reduce the risk of HF hospitalization.

The other comorbidities that the guidelines take aim at are anemia and iron deficiency in HF patients.

“We had the IRONMAN and four meta-analyses, all consistently showing a reduction in recurrent heart failure hospitalizations or cardiovascular death or total heart failure hospitalizations or cardiovascular death,” Metra noted.

The committee gave a class IA recommendation to IV iron supplementation in symptomatic patients with HFrEF or HFmrEF to alleviate HF symptoms and improve quality of life. The other new recommendation is a class IIa, level of evidence A, “to treat iron deficiency with ferric carboxymaltose or ferric derisomaltose in patients with HFrEF or HFmrEF to reduce their risk of heart failure hospitalization,” Metra added.

McDonagh noted that HEART-FID, which was just presented at ESC, may raise a question for some about the role of ferric carboxymaltose (FCM) in HFrEF. HEART-FID missed its primary endpoint, although a meta-analysis combining HEART-FID patients with those from CONFIRM-HF and AFFIRM-AHF, showed that FCM significantly reduced total cardiovascular hospitalizations and cardiovascular death compared with placebo (rate ratio 0.86; 95% CI 0.75-0.98).

In the guidelines session, McDonagh asked task force member Ewa A. Jankowska, MD (Wroclaw Medical University, Poland), if she thought the guideline committee “got it right” with regard to iron supplementation.

“I do believe that the totality of evidence is in favor of using this treatment and . . . moreover, there are several cardiovascular avenues which require our attention in the context of intravenous therapy, like pulmonary hypertension and HFpEF, [and] like acute MI, so definitely this is the next stage regarding using intravenous iron in cardiology,” Jankowska said.