Cardiovascular Outcome in Patients Treated With SGLT2 Inhibitors for Heart Failure: A Meta-Analysis

Abstract

Background: Sodium–glucose co-transporter 2 (SGLT2) inhibitors are an emerging class of glucose-lowering drugs that have become increasingly relevant for the treatment and prevention of heart failure (HF). Therefore, we aimed to investigate various SGLT2 inhibitors in patients with established HF at baseline and focused on the different types of HF.Methods: An extensive search of PubMed and Web of Science until January 2021 was done. Two reviewers, independently and in duplicate, applied the selection criteria. This meta-analysis was conducted according to the PRISMA guidelines. Data were pooled using a random-effects model. Randomized controlled trials (RCTs) of SGLT2 inhibitors vs. a comparator in patients with HF reporting clinical outcomes were included. The primary efficacy outcome was the composite of hospitalization for HF (HHF) or cardiovascular (CV) mortality. All-cause mortality, CV mortality, and HHF were considered as secondary endpoints. Subgroup analyses involving the status of diabetes, type of HF, administered type of SGLT2 inhibitor, sex, age, body mass index (BMI), estimated glomerular filtration rate (eGFR), cause of HF, and concomitant medication were performed.Results: Seventeen RCTs, comprising a total of 20,749 participants, were included (n = 10,848 treated with SGLT2 inhibitors and n = 9,901 treated with a comparator). Treatment with SGLT2 inhibitors in a HF population was associated with a 27% relative risk reduction (RRR) of HHF or CV mortality [risk ratio (RR) = 0.73, 95% CI = 0.68–0.78], 32% RRR of HHF (RR = 0.68, 95% CI = 0.62–074), 18% RRR of CV mortality (RR = 0.82, 95% CI = 0.73–0.91), and 17% RRR of all-cause mortality (RR = 0.83, 95% CI = 0.75–0.91). The effect of SGLT2 inhibitors on the primary endpoint was consistent among the different gliflozines. The effect of SGLT2 inhibitors on the primary endpoint was independent of underlying diabetes mellitus, age, sex, BMI, renal function, and HF type.Conclusions: SGLT2 inhibitors are associated with improved CV outcomes in patients with HF.

Commentary: Cardiovascular Outcome in Patients Treated With SGLT2 Inhibitors for Heart Failure: A Meta-Analysis

“…In summary, based on the findings from the meta-analysis of Gager et al (1) and ours, SGLT2 inhibitors should be recommended in a broad population of patients with HF patients, those with diabetes or not, those with reduced eGFR or not, and those with preserved/reduced LVEF. Moreover, SGLT2 inhibitors should be more recommended in Asian and Black patients with HF and patients with HF and with NYHA class II because of the greater benefits of this drug class in these HF subpopulations.…”

“…The meta-analysis of Gager et al ( 1 ) confirmed the consistent efficacy of SGLT2 inhibitors on the composite HF outcome (i.e., a composite of HHF/CVM) in various HF subgroups defined by several important factors, such as baseline diabetes status, type of SGLT2 inhibitors, and baseline level of eGFR. However, Gager et al ( 1 ) failed to perform subgroup analyses according to three other important factors: region, race, and baseline NYHA class. Thus, their findings ( 1 ) could not guide whether SGLT2 inhibitors should be used in patients with HF patients living in a specific region, those with a specific race, or those with a specific NYHA class.…”

“…However, Gager et al ( 1 ) failed to perform subgroup analyses according to three other important factors: region, race, and baseline NYHA class. Thus, their findings ( 1 ) could not guide whether SGLT2 inhibitors should be used in patients with HF patients living in a specific region, those with a specific race, or those with a specific NYHA class. Furthermore, Gager et al ( 1 ) also failed to include the latest CVOT of gliflozins, namely, EMPEROR-Preserved ( 2 ).…”

“…In the meta-analysis of Gager et al ( 1 ) recently published in the journal Frontiers in Cardiovascular Medicine , the authors identified that sodium-glucose co-transporter-2 (SGLT2) inhibitors could reduce heart failure (HF) events and all-cause mortality in patients with HF and that the benefit of this drug class on the primary endpoint (i.e., a composite of hospitalization for HF HHF) or cardiovascular mortality (CVM) was consistent across relevant HF subgroups defined by the following clinically important factors: the status of type 2 diabetes at baseline, type of HF (according to left ventricular ejection fraction, LVEF), cause of HF, specific SGLT2 inhibitors, gender, age, estimated glomerular filtration rate (eGFR), body mass index, and concomitant medications. However, Gager et al ( 1 ) failed to evaluate the effect of SGLT2 inhibitors in several subgroups defined by three other clinically important factors: race, region, and baseline New York Heart Association (NYHA) class. Hence, we aimed to conduct another meta-analysis to examine whether these factors affect the efficacy of gliflozins in patients with HF or not.…”

“…Moreover, Gager et al in their meta-analysis ( 1 ), failed to include the latest EMPEROR-Preserved trial ( 2 ) assessing empagliflozin in patients with HF with an LVEF of > 40%. Since that trial ( 2 ) provided the new data in the subgroup of HF with mildly reduced LVEF (HFmrEF) and the subgroup of HF with preserved LVEF (HFpEF), we repeated the subgroup analysis according to LVEF by adding these new data, although this subgroup analysis had been performed in the meta-analysis of Gager et al ( 1 ).…”