Conference Coverage

Black HFrEF patients get more empagliflozin benefit in EMPEROR analyses


AT AHA 2022

Race-linked treatment responses only in HFrEF

This suggestion of an imbalance in treatment efficacy was especially apparent among patients with HFrEF. In addition to the heterogeneity for the primary outcome, the Black and White subgroups also showed significantly divergent results for the outcomes of first hospitalization for heart failure, with a nonsignificant 21% relative reduction with empagliflozin treatment in Whites but a significant 65% relative cut in this endpoint with empagliflozin in Blacks, and for total hospitalizations for heart failure, which showed a similar level of significant heterogeneity between the two race subgroups.

In contrast, the patients with HFpEF showed no signal at all for heterogeneous outcome rates between Black and White subgroups.

One other study outcome, change in symptom burden measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), also showed suggestion of a race-based imbalance. The adjusted mean difference from baseline in the KCCQ clinical summary score was 1.50 points higher with empagliflozin treatment, compared with placebo among all White patients (those with HFrEF and those with HFpEF), and compared with a 5.25-point increase with empagliflozin over placebo among all Black patients with heart failure in the pooled American EMPEROR dataset, a difference between White and Black patients that just missed significance (P = .06). Again, this difference was especially notable and significant among the patients with HFrEF, where the adjusted mean difference in KCCQ was a 0.77-point increase in White patients and a 6.71-point increase among Black patients (P = .043),

These results also appeared in a report published simultaneously with Dr. Verma’s talk.

But two other analyses that assessed a possible race-based difference in empagliflozin’s effect on renal protection and on functional status showed no suggestion of heterogeneity.

Dr. Verma stressed caution about the limitations of these analyses because they involved a relatively small number of Black patients, and were possibly subject to unadjusted confounding from differences in baseline characteristics between the Black and White patients.

Black patients also had a number-needed-to-treat advantage with dapagliflozin

The finding that Black patients with heart failure potentially get more bang for the buck from treatment with an SGLT2 inhibitor by having a lower number needed to treat also showed up in a separate report at the meeting that assessed the treatment effect from dapagliflozin (Farxiga) in Black and White patients in a pooled analysis of the DAPA-HF pivotal trial of patients with HFrEF and the DELIVER pivotal trial of patients with HFpEF. The pooled cohort included a total of 11,007, but for the analysis by race the investigators also limited their focus to patients from the Americas with 2,626 White patients and 381 Black patients.

Dr. Jawad H. Butt, Rigshospitalet, Copenhagen Mitchel L. Zoler/MDedge News

Dr. Jawad H. Butt

Assessment of the effect of dapagliflozin on the primary outcome of cardiovascular death or hospitalization for heart failure among all patients, both those with HFrEF and those with HFpEF, again showed that event rates among patients treated with placebo were significantly higher in Black, compared with White patients, and this led to a difference in the number needed to treat to prevent one primary outcome event of 12 in Blacks and 17 in Whites, Jawad H. Butt, MD said in a talk at the meeting.

Although treatment with dapagliflozin reduced the rate of the primary outcome in this subgroup of patients from the DAPA-HF trial and the DELIVER trial by similar rates in Black and White patients, event rates were higher in the Black patients resulting in “greater benefit in absolute terms” for Black patients, explained Dr. Butt, a cardiologist at Rigshospitalet in Copenhagen.

But in contrast to the empagliflozin findings reported by Dr. Verma, the combined data from the dapagliflozin trials showed no suggestion of heterogeneity in the beneficial effect of dapagliflozin based on left ventricular ejection fraction. In the Black patients, for example, the relative benefit from dapagliflozin on the primary outcome was consistent across the full spectrum of patients with HFrEF and HFpEF.

EMPEROR-Reduced and EMPEROR-Preserved were sponsored by Boehringer Ingelheim and Lilly, the companies that jointly market empagliflozin (Jardiance). The DAPA-HF and DELIVER trials were sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Verma has received honoraria, research support, or both from AstraZeneca, Boehringer Ingelheim, and Lilly, and from numerous other companies. Dr. Butt has been a consultant to and received travel grants from AstraZeneca, honoraria from Novartis, and has been an adviser to Bayer.


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