CHICAGO – Black patients with heart failure with reduced ejection fraction (HFrEF) may receive more benefit from treatment with a sodium-glucose cotransporter-2 (SGLT2) inhibitor than do White patients, according to a new report.
A secondary analysis of data collected from the pivotal trials that assessed the SGLT2 inhibitor empagliflozin in patients with HFrEF, EMPEROR-Reduced, and in patients with heart failure with preserved ejection fraction (HFpEF), EMPEROR-Preserved, was presented by Subodh Verma, MD, PhD, at the American Heart Association scientific sessions.
Mitchel L. Zoler/MDedge News
Dr. Subodh Verma
The “hypothesis-generating” analysis of data from EMPEROR-Reduced showed “a suggestion of a greater benefit of empagliflozin” in Black, compared with White patients, for the study’s primary endpoint (cardiovascular death or hospitalization for heart failure) as well as for first and total hospitalizations for heart failure, he reported.
However, a similar but separate analysis that compared Black and White patients with heart failure who received treatment with a second agent, dapagliflozin, from the same SGLT2-inhibitor class did not show any suggestion of heterogeneity in the drug’s effect based on race.
Race-linked heterogeneity in empagliflozin’s effect
In EMPEROR-Reduced, which randomized 3,730 patients with heart failure and a left ventricular ejection fraction of 40% or less, treatment of White patients with empagliflozin (Jardiance) produced a nonsignificant 16% relative reduction in the rate of the primary endpoint, compared with placebo, during a median 16-month follow-up.
By contrast, among Black patients, treatment with empagliflozin produced a significant 56% reduction in the primary endpoint, compared with placebo-treated patients, a significant heterogeneity (P = .02) in effect between the two race subgroups, said Dr. Verma, a cardiac surgeon and professor at the University of Toronto.
The analysis he reported used combined data from EMPEROR-Reduced and the companion trial EMPEROR-Preserved, which randomized 5,988 patients with heart failure and a left ventricular ejection fraction greater than 40% to treatment with either empagliflozin or placebo and followed them for a median of 26 months.
To assess the effects of the randomized treatments in the two racial subgroups, Dr. Verma and associates used pooled data from both trials, but only from the 3,502 patients enrolled in the Americas, which included 3,024 White patients and 478 Black patients. Analysis of the patients in this subgroup who were randomized to placebo showed a significantly excess rate of the primary outcome among Blacks, who tallied 49% more of the primary outcome events during follow-up than did White patients, Dr. Verma reported. The absolute rate of the primary outcome without empagliflozin treatment was 13.15 events/100 patient-years of follow-up in White patients and 20.83 events/100 patient-years in Black patients.
The impact of empagliflozin was not statistically heterogeneous in the total pool of patients that included both those with HFrEF and those with HFpEF. The drug reduced the primary outcome incidence by a significant 20% in White patients, and by a significant 44% among Black patients.
But this point-estimate difference in efficacy, when coupled with the underlying difference in risk for an event between the two racial groups, meant that the number-needed-to-treat to prevent one primary outcome event was 42 among White patients and 12 among Black patients.