In April, the American College of Cardiology (ACC), American Heart Association (AHA) and the Heart Failure Society of America (HFSA) issued new joint guidelines for managing patients with heart failure. The most striking update to the guidelines is the addition of sodium-glucose co-transporter 2 inhibitors or SGLT2 inhibitors to guideline-directed medical therapy.
This class of medications, which includes dapagliflozin, empagliflozin and canagliflozin, inhibits the SGLT2 receptor in the proximal segment of the loop of Henle and results in increased natriuresis and glucosuria. By increasing glucose and sodium excretion, SGLT2 inhibitors can lower blood pressure, improve arterial stiffness, decrease weight, and improve A1C. Studies have shown that SGLT2 inhibitors reduce heart failure hospitalizations and cardiovascular death in patients with established heart failure and reduced ejection fraction.
“This is one of the most exciting drug classes to hit the market in a decade. Not often do we see groundbreaking therapies emerge in a relatively short period of time,” says Timothy Gong, MD, FACC, Assistant Medical Director, Advanced Heart Failure Outreach, Baylor University Medical Center at Dallas (Baylor Dallas), part of Baylor Scott & White Health. “Guideline-directed medical therapy for heart failure with reduced ejection fraction now recommends four medication classes that now include SGLT2 inhibitors. Notably, SGLT2 inhibitors have a Class 1 recommendation similar to beta blockers, ARNIs, ACE inhibitors and MRAs for heart failure with reduced ejection fraction.”
In the new ACC/AHA/HFSA guidelines, SGLT2 inhibitors have a Class 2a recommendation for heart failure with preserved ejection fraction, compared with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor-neprilysin inhibitor (ARNIs), angiotensin receptor blockers (ARBs), mineralcorticoid receptor antagonists (MRAs) and beta blockers, which carry a weaker Class 2b recommendation. Similarly, in heart failure with mildly reduced ejection fraction SGLT2 inhibitors also have a Class 2a recommendation. Previously, the options for these patients were poor.
The results of two particular clinical trials contributed to SGLT2 inhibitors being included in the new ACC/AHA/HFSA guidelines. The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial looked at the efficacy and safety of dapagliflozin in more than 4,700 patients with heart failure and reduced ejection fraction, whether or not the patients had diabetes. Among these patients, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes.
Another major trial – EMPEROR-Reduced – evaluated the safety and efficacy of empagliflozin versus placebo on top of guideline-directed medical therapy in more than 3,700 patients with a diagnosis of heart failure and reduced ejection fraction. The primary endpoint was the time to first event of cardiovascular death or hospitalization for worsening heart failure. The results were similar to tDAPA-HF. Among patients who were receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of the composite of cardiovascular death and heart failure hospitalization than those in the placebo group, whether they had diabetes or not.
“These trials really put SGLT2 inhibitors on the map,” Dr. Gong says. “Currently, 6.5 million adults in the United States live with heart failure, and that number is projected to rise to more than 8 million by 2030. These new drugs are a very valuable addition to our treatment armamentarium.”