Effectiveness and safety of angiotensin receptor-neprilysin inhibitor and sodium–glucose cotransporter-2 inhibitors for patients with heart failure with reduced ejection fraction: a meta-analysis

Yun Huang; Chongbo Fang; YuYu Zhang; Lili Ma; Hua Zhou; Honghua Ye

doi:10.2459/jcm.0000000000001426

December 30, 2022Journal of Cardiovascular Medicine

Effectiveness and safety of angiotensin receptor-neprilysin inhibitor and sodium–glucose cotransporter-2 inhibitors for patients with heart failure with reduced ejection fraction: a meta-analysis

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Why the study?

The study aimed to assess the effectiveness and safety of ARNI combined with SGLT2 inhibitors versus ARNI or SGLT2 inhibitor monotherapy in patients with HFrEF.

Does ARNI combined with SGLT2 inhibitors reduce cardiovascular events and mortality compared to ARNI or SGLT2 inhibitors monotherapy in patients with HFrEF?

Structured PICO

Does ARNI combined with SGLT2 inhibitors reduce cardiovascular events and mortality compared to ARNI or SGLT2 inhibitors monotherapy in patients with HFrEF?

P

Population

Patients with heart failure with reduced ejection fraction (HFrEF)

I

Intervention

Angiotensin receptor-neprilysin inhibitor (ARNI) combined with sodium-glucose cotransporter-2 (SGLT2) inhibitors

C

Comparator

ARNI or SGLT2 inhibitors monotherapy

O

Outcome

Composite of the first hospitalization for heart failure or cardiovascular deathcomposite

The combination of ARNI and SGLT2 inhibitors significantly reduces cardiovascular events and mortality in HFrEF compared to monotherapy with either agent, though it increases the risk of volume depletion.

Implication

Supports combined ARNI-SGLT2 inhibitor use in HFrEF; extends monotherapy trial data with additive benefit.

Abstract

The current review aimed to study the effectiveness and safety of angiotensin receptor-neprilysin inhibitor (ARNI) combined with sodium-glucose cotransporter-2 (SGLT2) inhibitors versus ARNI or SGLT2 inhibitors monotherapy in patients with heart failure with reduced ejection fraction (HFrEF). Studies containing patients with HFrEF who used ARNI combined with SGLT2 inhibitors versus ARNI or SGLT2 inhibitors alone were retrieved from the Medline, Embase, and Cochrane Library databases. From the selected studies, the pooled risk ratios with 95% confidence intervals of dichotomous outcomes were assessed by a random or fixed effects model in our meta-analysis. Compared with ARNI monotherapy, the reduction in ARNI combined with SGLT2 inhibitors in a composite of the first hospitalization for heart failure or cardiovascular death was 32%, hospitalization for heart failure was 35% and cardiovascular death was 35%; also all-cause death was 30%, worsening renal function was 35%, respectively, for patients with HFrEF. In addition, compared with SGLT2 inhibitors monotherapy, the reduction in ARNI combined with SGLT2 inhibitors in cardiovascular death was 36% and all-cause death was 28%, respectively, for patients with HFrEF. Although the estimated treatment effect is a 55% increase in volume depletion, overall, ARNI combined with SGLT2 inhibitors might be effective and safe for patients with HFrEF, and volume depletion should be given more attention.