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EMPA-REG Outcome: Empagliflozin reduces risk for HF endpoints
ORLANDO, Fla. — Empagliflozin, an SGLT2 inhibitor, is associated with decreased risk for HF hospitalization or CV death and other HF-related endpoints, according to new data from the EMPA-REG Outcome study.
The benefit was consistent regardless of whether patients had HF at baseline, researchers found.
Results of the primary outcome, indicating that empagliflozin (Jardiance, Boehringer Ingelheim) reduced risk for CV death/nonfatal MI/nonfatal stroke, were presented in September. The drug was also associated with a reduction in all-cause mortality. Silvio E. Inzucchi, MD, professor of endocrinology and director of the Yale Diabetes Center at Yale School of Medicine, presented results of other endpoints at the American Heart Association Scientific Sessions.
Silvio E. Inzucchi
The FDA requires that all diabetes drugs undergo testing for CV outcomes. Empagliflozin was the first to demonstrate a CV benefit.
HF outcomes are important in patients with diabetes because those with both conditions have a median survival of only 4 years, and glucose-lowering agents have shown no benefit, and possibly harm in some cases, for HF, Inzucchi said at a press conference, noting that his group previously presented findings showing that empagliflozin was associated with a reduction in HF hospitalization.
Inzucchi and colleagues randomly assigned 7,020 patients with diabetes and CVD to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo, all in addition to standard care. Mean follow-up was 3.1 years.
The benefit in the primary outcome was driven by a reduction in CV death (HR = 0.62; 95% CI, 0-49-0.77), Inzucchi said. “This was the most striking outcome,” he said.
The secondary endpoint of HF hospitalization or CV death also favored empagliflozin over placebo (HR = 0.66; 95% CI, 0.55-0.79), he said. This was true regardless of dose (HR for 10 mg = 0.66; 95% CI, 0.53-0.83; HR for 25 mg = 0.65; 95% CI, 0.52-0.81).
The endpoint of HF hospitalization or death from HF also favored empagliflozin (HR = 0.61; 95% CI, 0.47-0.79), according to the researchers, who also found that the drug was associated with fewer investigator-reported cases of HF and investigator-reported cases of serious HF.
Hospitalization for HF was reduced both in patients with and without HF at baseline, Inzucchi said. For those without HF at baseline, the difference was statistically significant (HR = 0.59; 95% CI, 0.43-0.82), while for those with HF at baseline, the difference was not statistically significant because of a small sample size, approximately 10% of the overall cohort (empagliflozin groups, 10.4%; placebo group, 12.3%; HR = 0.75; 95% CI, 0.48-1.19), he said.
A similar breakdown was observed in the endpoint of HF hospitalization or CV death (without HF: HR = 0.63; 95% CI, 0.51-0.78; with HF: HR = 0.72; 95% CI, 0.5-1.04), he said.
“There was no heterogeneity of effectiveness — i.e., not statistical interaction,” Inzucchi told Cardiology Today. “This indicates that there is no difference in the risk reduction seen in those with vs. without HF at baseline.
“In patients with type 2 diabetes and high CV risk, empagliflozin, given in addition to standard of care, reduced [HF] hospitalization or CV death, with a consistent benefit observed in both those with and without [HF] at baseline,” he said at the press conference. – by Erik SwainReference:
Inzucchi SE, et al. LBCT II: Decreasing the Global Burden of Disease: Breakthroughs in Prevention. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.
Disclosures: The study was funded by Boehringer Ingelheim. Inzucchi reports consulting for or receiving nonfinancial support from Boehringer Ingelheim, Eli Lilly, Intarcia, Janssen Pharmaceuticals, Lexicon, Merck, Novo Nordisk, Poxel, Sanofi/Regeneron and Takeda, and receiving research grants via his institution from Abbott, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk and Sanofi.
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What we heard today was more specific information about prevention of HF. HF is a major problem for patients with diabetes. There have been signals of increased risk for HF with some other diabetes medications. This has been an area of real concern and careful focus when considering and evaluating new drugs for diabetes. A drug that looks like it reduces risk for HF is very promising.
There are several reasons why people with diabetes might have HF. In some cases, it appears to be related to diastolic dysfunction and fibrosis. It’s possible that this medication might reduce the development of that form of HF. But we would need studies that look at myocardial fibrosis to understand that. Other patients with diabetes get HF through a more typical atherosclerotic ischemic cardiomyopathy mechanism. This medication certainly seems to reduce the risk for MI in patients with diabetes, so that’s another possible mechanism where it could affect HF.
This very well might change the decision-making process for prescribing diabetes drugs. Among the drugs that we have for diabetes, there are relatively few that have shown potential for reduction of conditions such as heart disease, HF and stroke. In my view, these findings would raise this drug to a much higher place on the list for selection. We need to see what careful review by a guideline committee would suggest after looking at the totality of the evidence. This is one study. Guidelines typically change slowly in response to more robust evidence. But this study is very promising, and it’s likely to change enthusiasm for the use of this medication relative to other medications.