The Effect of Empagliflozin on Risk for Heart Failure Events After Hospitalization

Regardless of recency of hospitalization for heart failure (HF), treatment with empagliflozin reduces risk for HF events. These findings were published in the Journal of the American College: Heart Failure.

An international team of investigators aimed to explore outcomes among patients with prior HF hospitalization subsequently treated with empagliflozin. The primary composite outcome was time to first HF hospitalization or cardiovascular death.

The researchers conducted a post hoc analysis of the EMPEROR-Pooled trial, which contained data from the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic HFrEF; ClinicalTrials.gov Identifier: NCT03057977) and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic HFpEF; ClinicalTrials.gov Identifier: NCT03057951) trials.

Combined, these studies included 9718 patients with HF grouped according to how recently they were hospitalized for HF (never [n=6270], <3 months [n=1050], 3-6 months [n=734], 6-12 months [n=736], and >12 months [928]). Patients with a more recent HF hospitalization tended to have lower blood pressure, higher heart rate, higher pro-B-type natriuretic peptide levels, and were more likely to be younger men. Median follow-up time was 21 months.

The primary endpoint event rates per 100 person-years in the placebo group were the following:

• 26.7 in patients in the less than 3 months group
• 18.1 in patients in the 3 to 6 months group
• 13.7 in patients in the 6 to 12 months group
• 2.8 in patients in the over 12 months group

Less than 3% of patients had hospitalization within 1 month of inclusion. A higher risk for primary endpoint events was noted in patients without prior HF hospitalization (10.6) vs patients hospitalized more than 12 months prior to enrollment (2.8).

When patients were treated with empagliflozin, the relative risk reduction for the primary outcome events was similar across all HF hospitalization timing categories (P_interaction =.67).

Among patients with a recent HF hospitalization, the primary endpoint absolute risk reduction (without statistical heterogeneity of treatment effect) in events prevented per 100 person-years were the following:

• -6.9 in patients in the less than 3 months group
• -5.5 in patients in the 3 to 6 months group
• -0.8 in patients in the 6 to 12 months group
• -0.6 in patients in the more than 12 months group
• -2.4 in patients without prior HF hospitalization

Regardless of HF hospitalization timing category, there was an overall neutral effect of empagliflozin on cardiovascular mortality (<3 months [hazard ratio {HR}, 0.71; 95% CI, 0.51-1.00]; 3-6 months [HR, 0.87; 95% CI, 0.55-1.37]; 6-12 months [HR, 1.19; 95% CI, 0.74-1.93]; >12 months [HR, 0.80; 95% CI, 0.43-1.49]).

Limitations of the study include its limited power to assess within-group treatment effects in timing subgroups for prior HF hospitalization, and lack of generalizability to patients hospitalized in the month prior to inclusion.

“Patients with a recent HF hospitalization, particularly if occurring within the previous 3 months, have a high risk of HF rehospitalization and mortality and experience large absolute benefit from empagliflozin treatment,” the study authors wrote. “These findings underscore the importance of initiating empagliflozin as early as possible within or early after an HF hospitalization, if not possible to initiate treatment to prevent a first HF hospitalization.”

Disclosure: This research (The EMPEROR-Reduced and Preserved trials) was supported by Boehringer Ingelheim and Eli Lilly. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.