Conference Coverage

SGLT2 inhibitors prevent HF hospitalization regardless of baseline LVEF



Patients who have type 2 diabetes and are taking a sodium-glucose cotransporter 2 (SGLT2) inhibitor have lower risks of heart failure hospitalization and all-cause mortality than patients on other glucose-lowering drugs regardless of whether their baseline left ventricular ejection fraction (LVEF) is preserved or reduced, based on data from a large real-world patient registry.

Dr. Mikhail Kosiborod

Dr. Mikhail Kosiborod

“The observed beneficial effects of SGLT2 inhibitors on heart failure may extend across the range of baseline ejection fractions,” Mikhail Kosiborod, MD, observed at the annual meeting of the American College of Cardiology.

This is an important new insight. The major randomized cardiovascular outcome trials that showed lower risks of heart failure hospitalization and all-cause mortality in type 2 diabetic patients on an SGLT2 inhibitor, such as EMPA-REG OUTCOME for empagliflozin (Jardiance) and CANVAS for canagliflozin (Invokana), didn’t include information on baseline LVEF. So until now it has been unclear whether the beneficial effects of the SGLT2 inhibitors preventing heart failure hospitalization vary depending upon LVEF, explained Dr. Kosiborod, a cardiologist at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

He presented an analysis drawn from the patient database kept by Maccabi Healthcare Services in Israel. The study included 5,307 patients with type 2 diabetes and an LVEF measurement recorded in their chart at the time they started on either empagliflozin or dapagliflozin (Farxiga) and an equal number of propensity-matched type 2 diabetic controls who started on other glucose-lowering drugs, most commonly an oral dipeptidyl peptidase-4 inhibitor.

During roughly 16,000 person-years of follow-up, 239 deaths occurred. Compared with patients on another glucose-lowering drug, the risk of death from all causes was reduced by 47% among patients who were on an SGLT2 inhibitor and had a baseline LVEF of 50% or greater and by 62% among the 9% of subjects who had a baseline LVEF less than 50%.

Incidence of key events in type 2 diabetes patients

Similarly, the risk of heart failure hospitalization was reduced by 29% in SGLT2 inhibitor users with a preserved LVEF and by 27% if they had a reduced LVEF.

For the composite endpoint of heart failure hospitalization or all-cause mortality, the risk reductions associated with SGLT2 inhibitor therapy were 45% with preserved and 39% with reduced LVEF.

Session comoderator Prakash C. Deedwania, MD, noted that there are ongoing major randomized trials of various SGLT2 inhibitors in patients with known heart failure, with cardiovascular death and heart failure hospitalization as primary endpoints. He asked Dr. Kosiborod whether, given that the results of these studies aren’t in yet, he thinks clinicians should be prescribing SGLT2 inhibitors to diabetic or prediabetic patients who don’t have clinical symptoms of heart failure but may have a marker of increased risk, such as an elevated B-type natriuretic peptide.

“At least in my mind, we have more than enough evidence at this point to say that SGLT2 inhibitors are effective in preventing heart failure,” Dr. Kosiborod replied.

“Obviously, if your risk for developing a condition is higher at baseline, then the absolute benefit that you’re going to get from using an agent that’s effective in preventing that event is going to be higher and the number needed to treat is going to be lower. So if you have a patient at high risk for heart failure by whatever risk predictor you’re using and the patient doesn’t yet have heart failure but does have diabetes, which is already a risk factor for heart failure, I think we have pretty solid data now that SGLT2 inhibitors will likely be effective in preventing heart failure in that kind of patient population. But I don’t think we have definitive data at this point to say that the drugs are effective in treating heart failure in people who already have a manifest clinical syndrome of heart failure, which is why we’re doing all these clinical trials now,” he continued.

Dr. Deedwania urged audience members to make the effort to become comfortable in prescribing SGLT2 inhibitors for their patients with type 2 diabetes.

“Many different surveys show that these drugs are not being utilized effectively by cardiologists,” noted Dr. Deedwania, professor of medicine at the University of California, San Francisco, and director of the heart failure program at the university’s Fresno campus.

“As cardiologists, we may not want to own diabetes, but we at least have to feel that we have the ownership of treating the diabetic patient with cardiovascular disease with appropriate drugs. We don’t need to depend on endocrinologists because if we do these patients may become lost,” he said.

Dr. Kosiborod concurred, citing evidence that diabetic patients with cardiovascular disease are much more likely to see a cardiologist than an endocrinologist in the course of usual care.

“There’s definitely a golden opportunity here to intervene to reduce risk,” he said.

Dr. Kosiborod reported serving as a consultant to roughly a dozen pharmaceutical companies.

SOURCE: Kosiborod M. ACC 19, Abstract #1024-07.

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