https://immattersacp.org/weekly/archives/2021/01/26/4.htm

ACC pathway supports neprilysin inhibitor, SGLT-2 inhibitors for heart failure with reduced ejection fraction

The American College of Cardiology (ACC) offered this update to their expert consensus decision pathway from 2017 as interim guidance to physicians while comprehensive updates to heart failure guidelines remain in development.


An updated decision pathway recommends the use of sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitors to streamline clinical care for optimal outcomes for patients with heart failure treatment for patients with reduced ejection fraction (HFrEF).

New therapies for HFrEF have emerged since the 2017 release of an expert consensus decision pathway from the American College of Cardiology, and the updated pathway expands treatment options and provides practical tips, tables, and figures to make clear the steps for treatment. It was published Jan. 11 by the Journal of the American College of Cardiology.

The first significant change is in support of the upfront use of the neprilysin inhibitor sacubitril/valsartan without angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) pre-treatment, based on data from the PARADIGM HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial showing a 4.7% reduction in the primary outcome of cardiovascular death or heart failure hospitalization compared to enalapril. The number of patients who would need to be treated to prevent one primary endpoint over 27 months was 21. In addition, the randomized EVALUATE-HF (Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction) trial showed an improvement in echocardiographic parameters of reverse cardiac remodeling as early as 12 weeks with treatment of sacubitril/valsartan compared to enalapril.

The second significantly updated recommendation is to use an SGLT-2 inhibitor for care of patients with HFrEF, with or without diabetes. This was based on evidence showing a reduced risk for major events (such as hospitalization or death) with the drugs regardless of the presence of diabetes, in trials such as the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), the DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction) trial, and EMPEROR-Reduced (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction). The pathway notes that SGLT-2 inhibitors lead to osmotic diuresis and natriuresis, decreases in arterial pressure and stiffness, and a shift to ketone-based myocardial metabolism. “Further benefits may be due to reduction of preload and afterload blunting of cardiac stress/injury with less hypertrophy and fibrosis, which would have favorable effects on myocardial remodeling,” the pathway stated.

In total, the pathway addresses 10 issues that the authors saw as pivotal to heart failure care, including initiating and optimizing guideline-directed therapies; addressing challenges of care coordination, adherence, and medication cost and access; providing for specific patient cohorts, including African Americans, older adults, and the frail; managing complexity and comorbidities; and integrating palliative care and the transition to hospice.

The updated pathway should serve as interim guidance to clinicians while awaiting the comprehensive and definitive heart failure guideline update under development by the ACC, according to its authors. “The treatment of HFrEF can feel overwhelming, and many opportunities to improve patient outcomes are being missed; hopefully, this [expert consensus decision pathway] will streamline care to realize the best possible patient outcomes in HF,” they wrote.