Two years is a long time in the world of heart failure (HF) management, enough to see publication of more than a dozen studies with insights that would supplant and expand key sections of a far-reaching European Society of Cardiology (ESC) clinical practice guideline on HF unveiled in 2021.
“Back in 2021, we had three and a half decades of data to consider,” but recent years have seen “an amazing amount of progress” that has necessitated some adjustments and key additions, including several Class I recommendations, observed Roy S. Gardner, MBChB, MD, Golden Jubilee National Hospital, Clydebank, United Kingdom.
The new document was also published in the European Heart Journal during the ESC sessions. Dr. Gardner is a co-author on both the 2021 and 2023 documents.
The task force that was charged with the focused update’s development “considered a large number of trials across the spectrum of acute chronic heart failure and the comorbidities associated with it,” Ultimately, it considered only those with “results that would lead to new or changed Class I or Class IIa recommendations,” noted Theresa A. McDonagh, MD, during the ESC sessions.
Dr. McDonagh, of King’s College Hospital, London, chaired the task force and led the document’s list of authors along with Marco Metra, MD, University of Brescia (Italy).
Chronic HF management
The 2021 document’s “beautiful algorithm” on managing HF with reduced ejection fraction, that is HF with an LVEF less than 40%, had helped enshrine the expeditious uptitration of the “four pillars” of drug therapy as a top management goal. That remains unchanged in the focused update, Dr. Gardner noted.
But the new document gives a boost to recommendations for HF with mildly reduced ejection fraction (HFmrEF), characterized by an LVEF greater than 40% to less than 50%. For that, the 2021 document recommended three of the four pillars of HF medical therapy: beta blockers, mineralocorticoid receptor antagonists (MRA), renin-angiotensin system (RAS) inhibitors.
The focused update, however, adds the fourth pillar – SGLT2 inhibitors – to core therapy for both HFmrEF and HF with preserved ejection fraction (HFpEF), the latter defined by an LVEF greater than 50%. Publication of trials supporting those new recommendations had narrowly missed availability for the 2021 document.
EMPEROR-Preserved, for example, was published during the same ESC 2021 sessions that introduced the 2021 guidelines. Its patients with HFpEF (which at the time included patients meeting the current definition of HFmrEF) assigned to the SGLT2 inhibitor empagliflozin (Jardiance) showed a 21% reduction in risk for a composite primary endpoint that was driven by the HF-hospitalization component.
“This wasn’t a fluke finding,” Dr. Gardner said, as the following year saw publication of the DELIVER trial, which resembled EMPEROR-Preserved in design and outcomes using the SGLT2 inhibitor dapagliflozin (Farxiga).
The two trials, backed up by meta-analyses that also included DAPA-HF and other studies, suggested as well that the two SGLT2 inhibitors “work across the spectrum of ejection fraction,” Dr. Gardner said.
The 2023 focused update indicates an SGLT2 inhibitor, either empagliflozin or dapagliflozin, for patients with either HFmrEF or HFpEF to reduce the risk of HF hospitalization or cardiovascular death. Both recommendations are of Class I, level of evidence A.
The new indications make SGLT2 inhibitors and diuretics (as needed for fluid retention) the only drugs for HFmrEF or HFpEF with a Class I recommendation. Previously established “rather weaker” Class IIb recommendation for RAS inhibitors, MRAs, and beta blockers that had been “based on subgroup analyses of neutral trials” remained unchanged in the focused update, Dr. McDonagh noted.