Effects of SGLT2 inhibitor not modified by the coexistence of AF in patients with HFpEF
In a secondary analysis of the EMPEROR-Preserved trial, the beneficial effects of empagliflozin on cardiovascular and renal outcomes were consistent in patients with HFpEF regardless of AF.
Empagliflozin in heart failure with preserved ejection fraction with and without atrial fibrillationLiterature - Filippatos G, Farmakis D, Butler J, et al. - Eur J Heart Fail. 2023 Jul;25(7):970-977. doi: 10.1002/ejhf.2861
Background
AF is common in patients with HFpEF [1], and the presence of AF is associated with worse outcomes in these patients [1-2]. In patients with HFrEF, the coexistence of AF is associated with impaired benefit of beta-blockers [3-4]. It remains unknown whether the beneficial effects of the SGLT2i empagliflozin are modified by the presence or absence of AF in patients with HFpEF.
Aim of the study
The aim of the study was to determine whether the coexistence of AF at baseline modifies the effects of empagliflozin in patients with HFpEF.
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Methods
This is a prespecified secondary analysis of EMPEROR-Preserved trial. The EMPEROR-Preserved trial was a double-blind, placebo-controlled trial in which 5988 patients with HF with EF >40% were randomized (1:1 ratio) to empagliflozin 10 mg daily or placebo. AF at baseline was defined as AF reported in a ECG before study treatment intake or medical history of AF. 3135 patients (52.4%) had AF at baseline, of whom 3131 patients (99.9%) had a history of AF and 2080 patients (66.3%) had AF according to baseline ECG. The median follow-up period was 26 months.
Outcomes
The primary outcome was time to first hospitalization for HF or CV death.
Main results
- The beneficial effects of empagliflozin on the risk of CV death or HF hospitalization were not modified by AF (HR: 0.78; 95%CI: 0.66-0.93; and HR: 0.78; 95%CI: 0.64-0.95; for patients with and without AF, respectively) (P for interaction=0.96).
- There was a consistent beneficial effect of empagliflozin treatment vs. placebo on the risk of first and recurrent HF hospitalization in patients with and without AF (HR: 0.73; 95%CI: 0.57-0.94; and HR: 0.72; 95%CI: 0.54-0.95; for patients with and without AF, respectively).
- Empagliflozin slowed the yearly decline in eGFR compared with placebo in patients with and without AF (slope difference, 1.37 ml/min/1.73 m² per year in both groups).
- The effects of empagliflozin on CV death, all-cause death, or renal outcomes were not modified by the coexistence of AF.
Conclusion
This pre-defined secondary analysis of EMPEROR-Preserved trial showed that empagliflozin reduces the risk of CV death or HF hospitalization in patients with HFpEF regardless of baseline AF compared with placebo. Moreover, empagliflozin slowed the yearly decline in renal function compared with placebo in patients with HFpEF with and without AF.
References
1. Sartipy U, Dahlström U, Fu M, Lund LH. Atrial fibrillation in heart failure with preserved, mid-range, and reduced ejection fraction. JACC Heart Fail. 2017;5(8):565-574.
2. Zafrir B, Lund LH, Laroche C, et al. Prognostic implications of atrial fibrillation in heart failure with reduced, mid-range, and preserved ejection fraction: a report from 14 964 patients in the European Society of Cardiology Heart Failure Long-Term Registry. Eur Heart J. 2018;39(48): 4277-4284.
3. Kotecha D, Flather MD, Altman DG, et al. Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure. J Am Coll Cardiol. 2017;69(24):2885-2896.
4. Filippatos G, Farmakis D. How to use beta-blockers in heart failure with reduced ejection fraction and atrial fibrillation. J Am Coll Cardiol. 2017;69(24):2897-2900.