Sodium-glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials

AimsWe sought to conduct a meta-analysis to evaluate the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF).MethodsWe searched the Cochrane Library, MEDLINE (via PubMed), Embase, and ClinicalTrials.gov till March 2023 to retrieve all randomized controlled trials of SGLT2i in patients with HFpEF or HFmrEF. Risk ratios (RRs) and standardized mean differences (SMDs) with their 95% conﬁdence intervals (95% CIs) were pooled using a random-effects model.ResultsWe included data from 14 RCTs. SGLT2i reduced the risk of the primary composite endpoint of first HF hospitalization or cardiovascular death (RR 0.81, 95% CI: 0.76, 0.87; I2 = 0%); these results were consistent across the cohorts of HFmrEF and HFpEF patients. There was no significant decrease in the risk of cardiovascular death (RR 0.96, 95% CI: 0.82, 1.13; I2 = 36%) and all-cause mortality (RR 0.97, 95% CI: 0.89, 1.05; I2 = 0%). There was a significant improvement in the quality of life in the SGLT2i group (SMD 0.13, 95% CI: 0.06, 0.20; I2 = 51%).ConclusionThe use of SGLT2i is associated with a lower risk of the primary composite outcome and a higher quality of life among HFpEF/HFmrEF patients. However, further research involving more extended follow-up periods is required to draw a comprehensive conclusion.Systematic Review RegistrationPROSPERO (CRD42022364223).

Section: Ef Diagnostic Thresholdsupporting

confidence: 81%

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors for heart failure with mildly reduced or preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials

Cheema,

Shafiee,

Athar

et al. 2023

“…Eight records were eliminated at this stage. Finally, 15 records (44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58) were included in this umbrella review. Figure 1 showed the literature screening procedure.…”

Section: Search Resultsmentioning

confidence: 99%

“…All included SRs/MAs were published in English, and the researchers were mainly from Asia and North America. Seven SRs/MAs were performed in China (45, 46, 42-54, 57, 58), 4 in The United States (44,48,50,51), and one each in India (47), Canada (49), Japan (55), and United Kingdom (57). Regarding intervention modality, the control group was given CT or placebo, whereas the intervention group was given various types of SGLT-2is, including "Canagliflozin," "Dapagliflozin," "Empagliflozin," "Ertugliflozin," "Ipragliflozin," "Luseogliflozin," and "Sotagliflozin".…”

Section: Characteristics Of Included Srs/masmentioning

confidence: 99%

Scientific evidence of sodium-glucose cotransporter-2 inhibitors for heart failure with preserved ejection fraction: an umbrella review of systematic reviews and meta-analyses

Dai

Guan

et al. 2023

BackgroundIt remains controversial whether sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are effective in treating heart failure with preserved ejection fraction (HFpEF).PurposeThe objective of this umbrella review is to provide a summary of the available evidence regarding the efficacy and safety of SGLT-2is for the treatment of HFpEF.MethodsWe extracted pertinent systematic reviews and meta-analyses (SRs/MAs) from PubMed, EMBASE, and the Cochrane Library that were published between the inception of the database and December 31, 2022. Two independent investigators assessed the methodological quality, risk of bias, report quality, and evidence quality of the included SRs/MAs in randomized controlled trials (RCTs). We further evaluated the overlap of the included RCTs by calculating the corrected covered area (CCA) and assessed the reliability of the effect size by performing excess significance tests. Additionally, the effect sizes of the outcomes were repooled to obtain objective and updated conclusions. Egger's test and sensitivity analysis were used to clarify the stability and reliability of the updated conclusion.ResultsThis umbrella review included 15 SRs/MAs, and their methodological quality, risk of bias, report quality, and evidence quality were unsatisfactory. The total CCA for 15 SRs/MAs was 23.53%, indicating a very high level of overlap. The excess significance tests did not reveal any significant results. Our updated MA demonstrated that the incidence of the composite of hospitalization for heart failure (HHF) or cardiovascular death (CVD), first HHF, total HHF, and adverse events as well as the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and 6 min-walk distance (6MWD) were all substantially improved in the SGLT-2i intervention group compared to the control group. However, there was limited evidence that SGLT-2is could improve CVD, all-cause death, plasma B-type natriuretic peptide (BNP) level, or plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level. Egger's test and sensitivity analysis proved that the conclusion was stable and reliable.ConclusionsSGLT-2 is a potential treatment for HFpEF with favourable safety. Given the dubious methodological quality, reporting quality, evidence quality, and high risk of bias for certain included SRs/MAs, this conclusion must be drawn with caution.Systematic Review Registrationhttps://inplasy.com/, doi: 10.37766/inplasy2022.12.0083, identifier INPLASY2022120083.

“…Some earlier meta-analyses that studied the outcome of SGLT2 inhibitors in heart failure patients did not focus solely on HFmrEF or HFpEF patients ( 12 , 51 ). Moreover, the meta-analyses that did set forth to focus on HFmrEF or HFpEF population did not extensively analyze the same outcome or specific subgroups as our meta-analysis had done ( 10 , 52 ). Our study also included an increase of at least 5 points in KCCQ score, which reflects new clinical impact on the aspect of patient QoL.…”

Section: Discussionmentioning

confidence: 99%

Is it time for class I recommendation for sodium-glucose cotransporter-2 inhibitors in heart failure with mildly reduced or preserved ejection fraction?: An updated systematic review and meta-analysis

Treewaree

Kulthamrongsri

Owattanapanich

et al. 2023

BackgroundIn heart failure with reduced ejection fraction (HFrEF), sodium-glucose cotransporter-2 (SGLT2) inhibitors were demonstrated to lower cardiovascular mortality (CV death) and hospitalization for heart failure (HHF); however, the advantages of SGLT2 inhibitors in heart failure with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) are less clear. SGLT2 inhibitors were reported to enhance quality of life (QoL) in HFmrEF or HFpEF patients; however, the findings among studies are inconsistent.ObjectiveTo conduct an updated systematic review and meta-analysis of recent data to assess the effect of SGLT2 inhibitors on cardiovascular outcomes and QoL in patients with HFmrEF or HFpEF.MethodThree databases were searched for studies that evaluated SGLT2 inhibitors and their effect on cardiovascular outcomes, including CV death, HHF, all-cause death, and the composite outcome of CV death, HHF, and urgent visit for heart failure (HF), and patient QoL (Kansas City Cardiomyopathy Questionnaire [KCCQ] score compared to baseline, and increase in KCCQ score ≥ 5 points) that were published during January 2000–August 2022. The meta-analysis was performed using the inverse variance method and random-effects model. INPLASY registration: INPLASY202290023.ResultsSixteen studies (9 recent RCTs) were included, and a total of 16,710 HFmrEF or HFpEF patients were enrolled. SGLT2 inhibitors significantly reduced composite cardiovascular outcome (CV death/HHF/urgent visit for HF; pooled hazard ratio [HR]: 0.80, 95% confidence interval [95%CI]: 0.74–0.86) and HHF alone (HR: 0.74, 95%CI: 0.67–0.82), but there was no significant reduction in CV death alone (HR: 0.93, 95%CI: 0.82–1.05). Benefit of SGLT2 inhibitors for decreasing CV death/HHF was observed across all subgroups, including left ventricular ejection fraction (LVEF) range, diabetes status, New York Heart Association functional class, and baseline renal function. For total HHF, SGLT2 inhibitors conferred benefit in both LVEF 50–60% (HR: 0.64, 95%CI: 0.54–0.76), and LVEF >60% (HR: 0.84, 95%CI: 0.71–0.98). Significant change was observed in the KCCQ-clinical summary score compared to baseline (mean difference: 1.33, 95%CI: 1.31–1.35), and meaningful improvement in QoL was shown across all 3 types of increase in KCCQ score ≥ 5 points.ConclusionThis study demonstrates the benefits of SGLT2 inhibitors for improving cardiovascular outcomes and QoL in HFmrEF or HFpEF patients.