Dataset Information

Influence of angiotensin receptor-neprilysin inhibition on the efficacy of Empagliflozin on cardiac structure and function in patients with chronic heart failure and a reduced ejection fraction: The Empire HF trial.

ABSTRACT:

Study objective

The objective was to assess the effect of ongoing angiotensin receptor-neprilysin inhibitor(ARNI) on the effect of the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) size and function in patients with heart failure and reduced ejection fraction(HFrEF).

Design

Post hoc analysis of the Empire HF trial, an investigator-initiated, double-blind, randomized controlled trial.

Participants

190 patients with HFrEF with New York Heart association class I-III symptoms with an ejection fraction of 40 % or below. Patients were stratified according to ongoing ARNI treatment at baseline.

Intervention

Empagliflozin 10 mg daily or placebo for 12 weeks. Echocardiography at baseline and follow-up.

Main outcome measures

Left ventricular end-systolic volume index (LVESVI), end-diastolic volume index (LVEDVI), left atrial volume index (LAVI), left ventricular ejection fraction (LVEF).

Results

A total of 58 patients (31 %) received ARNI at baseline. Compared to with placebo, empagliflozin reduced the LVESVI ([-6.2 (-14.1 to 1.6); p = 0.12] and [-3.3 (-8.2 to 1.6); p = 0.19], interaction P = 0.49), LVEDVI ([-11.2 (-21.2 to -1.2); p = 0.03] and [-2.9 (-8.7 to 2.9); p = 0.32], interaction P = 0.13), and LAVI ([-3.9 (-9.1 to 1.2); p = 0.14] and. [-1.8 (-4.4 to 0.7); p = 0.16], respectively, interaction P = 0.9) in patients treated with and without ARNI at baseline, respectively. No treatment-by-ARNI subgroup interaction were found. Unaffected by baseline ARNI treatment, empagliflozin did not improve LVEF.

Conclusion

The effect of empagliflozin on cardiac structure and function compared to placebo was not affected by background treatment with ARNI.

SUBMITTER: Larsen JH

PROVIDER: S-EPMC10946004 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Influence of angiotensin receptor-neprilysin inhibition on the efficacy of Empagliflozin on cardiac structure and function in patients with chronic heart failure and a reduced ejection fraction: The Empire HF trial.

Larsen Julie Hempel JH Omar Massar M Jensen Jesper J Andersen Camilla Fuchs CF Kistrup Caroline Michaela CM Poulsen Mikael Kjær MK Videbæk Lars L Gustafsson Finn F Køber Lars L Schou Morten M Møller Jacob Eifer JE

American heart journal plus : cardiology research and practice 20230203

<h4>Study objective</h4>The objective was to assess the effect of ongoing angiotensin receptor-neprilysin inhibitor(ARNI) on the effect of the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) size and function in patients with heart failure and reduced ejection fraction(HFrEF).<h4>Design</h4>Post hoc analysis of the Empire HF trial, an investigator-initiated, double-blind, randomized controlled trial.<h4>Participants</h4>190 patients with HFrEF with New Yor ...[more]

PMID: 38510180

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Project description:AimsWhether medication adherence to angiotensin receptor-neprilysin inhibitor (ARNI) in real-world practice is associated with the reduced risk of all-cause mortality or hospitalization relative to that with traditional renin-angiotensin system (RAS) blockade remains unclear. This study investigated the influence of medication adherence of ARNI and traditional RAS blockade in heart failure with reduced ejection fraction (HFrEF).MethodWe conducted a nationwide longitudinal cohort study with patients with HFrEF using data from the Korean National Health Insurance Service data (2017-2021) covering the entire population. A total of 13 483 patients with HFrEF who received ARNI were matched 1:1 with 13 483 patients who received traditional RAS blockade using propensity score matching. The primary outcome was a composite of all-cause mortality or any hospitalization within one year. Medication adherence was assessed by calculating the proportion of days covered (PDC) relative to total medication prescribed. ARNI and traditional RAS blockade adherence rates were directly compared to analyse their respective associations with the primary outcome.ResultsPatients in the ARNI group had a lower rate of the primary outcome than those in the traditional RAS blockade group [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.75-0.81; P < 0.001]. Mean PDC values spanning 1 year were 92.6 ± 14.5% and 90.9 ± 17.7% in the ARNI and RAS blockade groups, respectively (P < 0.001). Among patients with PDC ≥ 80%, the risk of primary outcome was significantly lower in the ARNI group than in the RAS blockade group (HR 0.75; 95% CI 0.72-0.78; P < 0.001) while a risk reduction with ARNI was not observed among patients with PDC < 80% (HR 0.95; 95% CI 0.85-1.05; P = 0.313). The beneficial effect was more pronounced among patients with PDC ≥ 80% than that among patients with PDC < 80% (P for interaction <0.001).ConclusionsIn a real-world cohort with HFrEF, ARNI was superior to traditional RAS blockade in reducing the risk of all-cause mortality and hospitalization. The benefit of ARNI was pronounced among patients with high medication adherence but not among those with low medication adherence, highlighting the importance of adherence to ARNI treatment for HFrEF.Trial registrationPARADE-HF ClinicalTrials.gov number, NCT05329727.

Project description:BackgroundFrail older adults may be less likely to receive guideline-directed medical therapy (GDMT)-renin-angiotensin blockers, beta-blockers, and mineralocorticoid receptor antagonists-for heart failure with reduced ejection fraction (HFrEF). We aimed to examine the uptake of angiotensin receptor neprilysin inhibitor (ARNI) and GDMT in frail older adults with HFrEF.MethodsUsing 2015-2019 Medicare data, we estimated the proportion of beneficiaries with HFrEF receiving ARNI and GDMT each year by frailty status, defined by a claims-based frailty index. Logistic regression was used to identify clinical characteristics associated with ARNI initiation. Cox proportional hazards regression was used to examine the association of GDMT use in 2015 and death or heart failure hospitalization in 2016-2019.ResultsAmong 147,506-180,386 beneficiaries with HFrEF (mean age: 77 years; 27% women; 42.6-49.1% frail) in 2015-2019, the proportion of patients receiving ARNI increased in both non-frail (0.4%-16.4%) and frail (0.3%-13.7%) patients (p for yearly-trend-by-frailty = 0.970). Among those not receiving a renin-angiotensin system blocker, patients with age ≥ 85 years (odds ratio [95% CI], 0.89 [0.80-0.99]), dementia (0.88 [0.81-0.96]), and frailty (0.87 [0.81-0.94]) were less likely to initiate ARNI. The proportion of patients receiving all 3 GDMT classes increased in non-frail patients (22.0%-27.0%) but changed minimally in frail patients (19.6%-21.8%). Regardless of frailty status, treatment with at least 1 class of GDMT was associated with lower death or heart failure hospitalization than no GDMT medications (hazard ratio [95% CI], 0.94 [0.91-0.97], 0.92 [0.89-0.94], 0.94 [0.91-0.97] for 1, 2, and 3 classes, respectively).ConclusionsOur results suggest an evidence-practice gap in the use of ARNI and GDMT in Medicare beneficiaries with HFrEF, particularly those with frailty. Efforts to narrow this gap are needed to reduce the burden of HFrEF in older adults.

Project description:Background There are limited data on the use of angiotensin receptor neprilysin inhibitors (ARNIs) in minority populations with heart failure (HF) with reduced ejection fraction. We used data from the CHAMP-HF (Change the Management of Patients With Heart Failure) registry to evaluate ARNI initiation and associated changes in health status and clinical outcomes across different races and ethnicities. Methods and Results CHAMP-HF was a prospective, observational registry of US outpatients with chronic HF with reduced ejection fraction. We compared patients starting ARNI with patients not starting ARNI using a propensity-matched analysis. Patients were grouped as Hispanic, non-Hispanic Black, non-Hispanic White, or non-Hispanic other individuals, where "non-Hispanic other" consists of all patients who did not identify as Hispanic, Black, or White. Health status was assessed using the 12-item Kansas City Cardiomyopathy Questionnaire. Outcomes were analyzed with multivariable models that included race and ethnicity, ARNI initiation, and an interaction term between race and ethnicity and ARNI initiation. Cox proportional hazards models were used for death/HF hospitalization, and multiple regression was used for change in Kansas City Cardiomyopathy Questionnaire score. The analysis included 1516 patients, with 758 patients in each group (ARNI and no ARNI). Changes in Kansas City Cardiomyopathy Questionnaire score after ARNI initiation were similar among all race and ethnicity groups (mean [SD], non-Hispanic White individuals, 3.5 [19.0]; non-Hispanic Black individuals, 2.0 [17.0]; non-Hispanic other individuals, 5.5 [20.3]; and Hispanic individuals, 3.2 [20.1]), with no statistically significant interaction between race and ethnicity and ARNI initiation (P=0.21). There was similarly no statistically significant interaction between race and ethnicity and ARNI initiation for HF hospitalization (P=0.82) or all-cause mortality (P=0.92). Conclusions In a large registry of outpatients with HF with reduced ejection fraction, the association between ARNI initiation and outcomes did not differ by race and ethnicity. These data support the use of ARNI therapy for chronic HF with reduced ejection fraction irrespective of race and ethnicity.

Project description:ImportanceSodium-glucose cotransporter-2 inhibitors (SGLT2i) improve outcomes in patients with heart failure and a reduced ejection fraction (HFrEF). The association with cardiac remodeling has not been investigated.ObjectiveTo investigate the outcome of the SGLT2i empagliflozin, compared with placebo, on cardiac remodeling in patients with HFrEF.Design, setting, and participantsThis exploratory post hoc analysis included participants with stable HFrEF and ejection fractions of 40% or less, who were randomly enrolled in an investigator-initiated, multicenter, double-blind, placebo-controlled randomized clinical trial in Denmark. Enrollment commenced on June 29, 2017, and continued through September 10, 2019, with the last participant follow-up on December 20, 2019.InterventionsRandomization (1:1) to empagliflozin (10 mg once daily) or matching placebo in addition to recommended heart failure therapy for 12 weeks.Main outcomes and measuresEfficacy measures were changes from baseline to week 12 in left ventricular end-systolic and end-diastolic volume indexes, left atrial volume index, and left ventricular ejection fraction adjusted for age, sex, type 2 diabetes, and atrial fibrillation. Secondary efficacy measures included changes in left ventricular mass index, global longitudinal strain, and relative wall thickness.ResultsA total of 190 patients were randomized (95 each receiving empagliflozin and placebo), with a mean (SD) age of 64 (11) years; 162 were men (85.3%), 97 (51.1%) had ischemic HFrEF, 24 (12.6%) had type 2 diabetes, and the mean (SD) latest recorded left ventricular ejection fraction was 29% (8%). Of the 190, 186 completed the study. Empagliflozin significantly reduced left ventricular end-systolic volume index (-4.3 [95% CI, -8.5 to -0.1] mL/m2; P = .04), left ventricular end-diastolic volume index (-5.5 [95% CI, -10.6 to -0.4] mL/m2; P = .03), and left atrial volume index (-2.5 [95% CI, -4.8 to -0.1] mL/m2; P = .04) compared with placebo at 12 weeks' follow-up, with no change in left ventricular ejection fraction (1.2% [95% CI, -1.2% to 3.6%]; P = .32). These findings were consistent across subgroups. Of secondary efficacy measures, left ventricular mass index was significantly reduced by empagliflozin (-9.0 [95% CI, -17.2 to -0.8] g/m2; P = .03).Conclusions and relevanceIn this small, randomized, short-term study, empagliflozin was associated with modest reductions in left ventricular and left atrial volumes with no association with ejection fraction. Effects beyond 12 weeks of SGLT2i use require further study.Trial registrationClinicalTrials.gov Identifier: NCT03198585.

Dataset Information

Influence of angiotensin receptor-neprilysin inhibition on the efficacy of Empagliflozin on cardiac structure and function in patients with chronic heart failure and a reduced ejection fraction: The Empire HF trial.

Study objective

Design

Participants

Intervention

Main outcome measures

Results

Conclusion

Publications

Influence of angiotensin receptor-neprilysin inhibition on the efficacy of Empagliflozin on cardiac structure and function in patients with chronic heart failure and a reduced ejection fraction: The Empire HF trial.

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