New ACC, AHA, HFSA Guidelines Recommend SGLT-2 Inhibitors for Symptomatic Heart Failure

The American College of Cardiology (ACC), American Heart Association (AHA) and Heart Failure Society of America (HSFA) have released a joint guideline addressing updates to heart failure prevention and treatment of symptomatic disease with the emerging SGLT-2 inhibitor drug class.

The new guideline—published and presented during the ACC 2022 Scientific Sessions in Washington DC—implement findings from trials including DAPA-HF and EMPEROR-HF, which previously shown the benefit of SGLT-2 inhibitors dapagliflozin and empagliflozin, respectively, in reducing composite cardiovascular events and mortality in patients with heart failure with reduced ejection fraction (HFrEF)—among other cardiovascular and cardiometabolic outcomes.

Additionally, the guideline puts further emphasis on primary heart failure prevention through measures including blood pressure control and changes to high-risk patients’ diet and exercise. More than 120 million Americans currently have high blood pressure; another 100 million are obese and 28 million have diabetes, meaning a significant rate of the US population can be categorized as at-risk for heart failure—or “Stage A,” per the new guideline risk stages.

Previous clinical recommendations from the ACC and AHA defined 4 stages of heart failure development and progression, defined categorically from A to D. In this newest guideline, the author committee set precedent for treating stage A patients prior to the development of structural changes or signs of worsened heart function that would indicate pre-disease stage B.

The 4 stages are as follows:

• Stage A: At risk for heart failure but without symptoms. Structural heart disease or blood tests indicate patient has heart muscle injury. Patients include those with high blood pressure, diabetes, metabolic syndrome, obesity, those exposed to medications or treatments that may damage the heart, and those at hereditary risk of heart failure.
• Stage B: Pre-heart failure stage. Patients do not have symptoms nor signs of disease, but are observed with structural heart disease—such as reduced ejection fraction, heart muscle enlargement, heart muscle contraction abnormalities, or valve disease. Ultrasounds may show increased filling pressures. Additionally, stage A risk factors may have progressed, B-type natriuretic peptide may be increased, or cardiac troponin may be consistently elevated.
• Stage C: Symptomatic heart failure. Patients have structural heart disease with current or previous symptoms including shortness of breath, persistent cough, swelling, fatigue and nausea.
• Stage D: Advanced heart failure, with symptoms impacting daily life routines, and difficult-to-control symptoms that result in recurrent hospitalization despite guideline-directed medical treatment.

Once patients reach stage C, clinicians use the New York Heart Association (NYHA) Classes I – IV to define functional capacity and specify treatment strategy.

The new guideline recommends normal resting blood pressure score below 120/80 mmHg for patients in stage A, while those with type 2 diabetes and either high cardiovascular disease risk or present disease are recommended to consider initiating SGLT-2 inhibitor therapy. Additionally, authors recommended improved physical activity, healthful dietary patterns, smoking avoidance, and healthy weight maintenance as part of risk prevention.

In stage B, the guideline now recommends patients with pre-heart failure receive additional medication to prevent progression to symptomatic disease in stage C. Those with left ventricle ejection fraction (LVEF) ≤40% are advised to be prescribed angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)—the latter if patients are intolerant or contraindicated to ACE inhibitors.

New symptomatic heart failure definitions at stage C from the guideline include:

• HFrEF: patients with LVEF ≤40%
• Heart failure with improved ejection fraction (HFimpEF): patients with previous ≤LVEF and a follow-up measurement of >40%
• Heart failure with mildly reduced ejection fraction (HFmrEF): patients with LVEF 41-49% and evidence of increased LV filling pressures
• Heart failure with preserved ejection fraction (HFpEF): patients with LVEF ≥50% and evidenced of increased LV filling pressures

For patients with HFrEF, the guideline recommends pharmacological intervention with 4 classes of medication, including diuretics: angiotensin receptor-neprilysin (ARN) inhibitors, ACE inhibitors or ARBs, mineralocorticoid recept antagonists (MRA) or beta blockers, and now SGLT-2 inhibitors—the latter being for patients with symptomatic chronic HFrEF regardless of type 2 diabetes status.

For patients with HFmrEF, the guideline recommends initial SGLT-2 inhibitor treatment along with as-needed diuretics. The authors deemed ARN and ACE inhibitors, ARBs, MRA and beta blockers as “weaker recommendations” for this population due to less-robust data than SGLT-2 inhibitors.

For patients with HFpEF, prevalent hypertension should be treated in accordance with previous clinical guidelines, while SGLT-2 inhibitors are now deemed potetnailly beneficial in decreasing composite cardiovascular mortality and hospitalization risk. Authors additionally recommend the management of atrial fibrillation to improve HFpEF symptoms. Patients with lower LVEF may be considered for MRA, ARBs and ARN inhibitors.

It was “careful evaluation of new evidence” from empiric heart failure-associated clinical trials that led to the introduction of SGLT-2 inhibitors in this new guideline, writing committee vice chair Biykem Bozkurt, MD, PhD, said in a statement accompanying the release.

“Irrespective of diabetes status, the DAPA-HF and EMPEROR-HF trials have shown the benefit of treating patients with HFrEF with SGLT-2 inhibitors, showing a 30% reduction in heart failure rehospitalization,” Bozkurt noted. “This is a major step forward in reducing mortality rates in this vulnerable population.”

Additionally provided throughout the new guideline are recommendations on managing heart failure in patients with comorbidities including iron deficiency, anemia, sleep disorders, cancer, and coronary artery disease. The authors also set precedent with new immunization recommendations, stating that patients with stage C symptomatic heart failure should be fully vaccinated against respiratory viruses including COVID-19.

Overall, the guideline provides recommendations with acknowledgement to the recent increases in game-changing clinical and pharmacotherapy data, as well as the increasingly diverse heart failure patient populations being encountered in the cardiovascular, cardiometabolic and cardiorenal fields.

“In recent years, there has been an increase in rigorous science assessing how best to treat symptomatic heart failure,” writing committee chair Paul A. Heidenreich, MD, MS, said. “With this new guideline, the writing committee hopes to inform better treatment options for a broader number of our patients with heart failure.”

The guideline, “2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary,” was presented at ACC 2022.