Empagliflozin CV Benefit Unaffected by HF Burden: EMPA-REG Analysis

Larry Hand

September 02, 2016

ROME, ITALY — Patients with type 2 diabetes and cardiovascular disease (CVD) can benefit from taking empagliflozin (Jardiance, Boehringer Ingelheim) whether they have heart failure, develop heart failure, or don't have heart failure, according to new research presented at the European Society of Cardiology (ESC) 2016 Congress[1].

"A person with diabetes who also has established cardiovascular disease will have a 12-year shorter life expectancy than a person without diabetes and CVD," Dr David Fitchett (St Mary's Hospital, University of Toronto, Canada), said during a clinical-trial update of the EMPA-REG OUTCOME trial. "The benefits [of empagliflozin] appeared extremely early during the treatment period and were sustained throughout the trial."

In the clinical update, he described further research that delved into "heart-failure burden" and the effects of empagliflozin vs placebo. Heart-failure burden is defined as the composite of heart failure at baseline, adjudicated hospitalization for heart failure during the trial, and investigator-reported heart failure during the trial.

The EMPA-REG trial randomized 7020 patients to receive either empagliflozin (10 mg or 25 mg) or placebo daily from September 2010 through April 2013. The primary outcome of the study was the combination of cardiovascular death, nonfatal MI, or nonfatal stroke.

The primary outcome occurred in 490 of 4687 (10.5%) of patients in the empagliflozin group, compared with 282 of 2333 (12.1%) of patients in the placebo group (hazard ratio [HR] 0.86; P<0.001 for noninferiority and P=0.04 for superiority).

Empagliflozin led to significantly lower risk of cardiovascular death (HR 0.62, P<0.001), death from any cause (HR 0.68, P<0.001), and hospitalization for heart failure (HR 0.65, P<0.002).

"The reduction in the primary end point was driven entirely by a 38% reduction in cardiovascular death," Fitchett said at the ESC congress.

In the new research since the trial, Fitchett and colleagues have assessed the impact of empagliflozin on heart-failure burden and its effects on heart-failure outcomes by analyzing cardiovascular death in subgroups of patients with prevalent and incident heart failure.

Patients with heart-failure burden in the empagliflozin experienced a 33% reduction in cardiovascular death, compared with patients in the placebo group (10.4% vs 15.3%, HR 0.67). Patients in the empagliflozin group without heart-failure burden experienced a 37% reduction in cardiovascular death, compared with patients in the placebo group (2.7% vs 4.2%, HR 0.63).

The research shows that the overall population has experienced an absolute mortality reduction of 2.2%. The heart-failure–burden population experienced an absolute mortality reduction of 4.9%, and the population without heart-failure burden experienced a 1.4% absolute mortality reduction.

"Empagliflozin is beneficial in persons who present with all types of heart failure," Fitchett said.

Earlier this year, a US Food and Drug Administration advisory committee narrowly recommended approval of new labeling for empagliflozin to include cardiovascular death reduction as a benefit. Researchers also discussed the drug's effect regarding heart failure at the American Heart Association 2015 Scientific Sessions.

The Boehringer Ingelheim & Eli Lilly Diabetes Alliance funded the EMPA-REG OUTCOME trial. Fitchett reported serving on advisory panels for Sanofi, AstraZeneca, and Merck and a data and safety monitoring board for Novo Nordisk and receiving speaker fees from Boehringer Ingelheim, Sanofi, AstraZeneca, and Merck. Disclosures for the coauthors are listed in the article.

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