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Key opinion leaders in the cardiometabolic space describe the importance of the introduction of SGLT2 inhibitors for heart failure treatment based on 2022 guidelines.
The significance of World Heart Day serves not only as a reminder of the global impact of cardiovascular disease (CVD), but as a marker of what the last 365 days represented for the field of cardiometabolic health.
Earlier this year, the American College of Cardiology (ACC), American Heart Association (AHA), and Heart Failure Society of America (HFSA) released joint guidelines on updates to heart failure prevention. By the guidelines' own phrasing, the evidence-based approach was designed to both improve quality of care and align with patients’ interests.
A primary interest in the update among clinicians was the introduction of the sodium-glucose cotransporter-2 (SGLT2) inhibitor drug class to guideline-directed medical therapy (GDMT) after clinical trial data demonstrated their ability to reduce composite cardiovascular events and mortality patients with heart failure with reduced ejection fraction (HFrEF).
“Those are big innovators and to see our cardiology colleagues using diabetes drugs, now everyone is a preventive cardiologist,” said Bob Busch, MD, Director of Clinical Research, Albany Medical College Endocrinology. “Not only the cardiologist, but primary care and endocrinologists are preventive cardiologists.”
This shift towards diabetic medicine, including the SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), were crucial advancements according to these prominent key opinion leaders in the cardiometabolic arena.
“Sometimes people don't fully appreciate how long that was chased, and how unsuccessfully it was chased,” said Jorge Plutzky, MD, Director of Preventive Cardiology, Harvard Medical School. “To have these drugs come along, that are significantly reducing cardiovascular events in the form of SGLT2 inhibitors and GLP-1 RAs, I think it is really a sea change in turning the page of opportunities.”
Landmark trials, including DAPA-HF and EMPEROR-Preserved, showed the benefit of agents like dapagliflozin and empagliflozin in reducing events in patients with HFrEF and heart failure with preserved ejection fraction (HFpEF), respectively. More recently, DELIVER has strengthened the notion these apparent benefits are true class effects.
“I would say SGLT2 inhibitors have changed my practice more than anything else in the last five years,” said Alison Bailey, MD, Physician Director, Cardiovascular Disease at HCA Healthcare. “Because we had to have cardiovascular outcomes data for diabetic trials, we saw an almost 40% reduction in developing heart failure, a reduction in chronic kidney disease or need for dialysis.”
The ability to provide these efficacious drugs to patients with heart failure with and without diabetes and is proven to reduce outcomes and HFpEF led to Bailey calling it the “biggest success story discussed in the last 5 years.”
In addition, the ACC/AHA/HFSA guidelines promoting the use of SGLT2 inhibitors also emphasized the 4 stages of heart failure progression, measured categorically from A to D. The “Stage A” patients included those at-risk for heart failure, but without symptoms, including those with high blood pressure, diabetes, and obesity.
Erin Michos, MD, Johns Hopkins School of Medicine, expressed excitement on trials regarding the GLP-1 RAs and their efficacy in battling obesity, including tirzepatide.
The agent was recently approved to improve blood sugar control in adults with diabetes, as the first in-class treatment that activates both the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).
“Obesity is a huge issue and it is difficult for patients to lose weight, but patients can get really significant weight loss, 30 to 50 pounds, with these agents,” said Erin Michos, MD, Associate Professor of Medicine, Division of Cardiology, Johns Hopkins School of Medicine. “We’re hopeful that these agents will reduce cardiovascular outcomes and patients without diabetes that have overweight and obesity, although those outcome trials are ongoing in that population.”
Plutzky shared a similar sentiment in weight loss, adding he is looking forward to the results of the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial on semaglutide 2.4 mg.
“We're looking forward to the results of the SELECT trial, which will look at GLP-1 RAs in people at high risk, who are overweight and obese, but who don't have diabetes,” he said. “I think that could be really important, as we have long tried to medicalize obesity.”
The introduction of these diabetic agents that were not only cardiovascular safe, but showed strong benefits for patients truly marked a new era for cardiometabolic care.
“We start out with a medicine that has an intended benefit to at least not harm our dibaetic patients from a cardiovascular standpoint, but we see that not only does it not harm our patients, but it prevents heart failure,” Bailey added.