Effects and safety of SGLT2 inhibitors compared to placebo in patients with heart failure: A systematic review and meta-analysis

Chambergo‐Michilot, Diego; Tauma‐Arrué, Astrid; Loli-Guevara, Silvana

doi:10.1016/j.ijcha.2020.100690

Cited by 20 publications

(33 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hence, our results provided more robust and comprehensive evidence for evaluating the effect of empagliflozin on HF. We observed significant improvements in heart failure hospitalizations and cardiovascular deaths, which is in line with a previous study ( 32 ) focused on the effect of SGLT2i in heart failure patients. However, regarding the two outcomes of a composite of cardiovascular death or hospitalization for worsening heart failure and hospitalization for worsening heart failure, our study showed greater RR reduction than the previous meta-analysis ( 32 ), which may indicate that empagliflozin is superior in patients with reduced ejection fraction.…”

Section: Discussionsupporting

confidence: 92%

“…We observed significant improvements in heart failure hospitalizations and cardiovascular deaths, which is in line with a previous study ( 32 ) focused on the effect of SGLT2i in heart failure patients. However, regarding the two outcomes of a composite of cardiovascular death or hospitalization for worsening heart failure and hospitalization for worsening heart failure, our study showed greater RR reduction than the previous meta-analysis ( 32 ), which may indicate that empagliflozin is superior in patients with reduced ejection fraction. It is also worth noting that the results of our study and a previous trial with dapagliflozin intervention ( 33 ) demonstrated no significant difference in the change in NT-proBNP.…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Pan

Lin

Chen

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Purpose: The purpose of the study is to evaluate the effect of empagliflozin in patients with heart failure (HF).Method: We performed a systematic search of PubMed, EMBASE, and the Cochrane Library database through January 20, 2021. Randomized controlled trials (RCTs) were included that compared empagliflozin and placebo in patients with HF. Dichotomous variables were expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Continuous variables were calculated and expressed as mean differences (MD) and standard deviation (SD). Meta-analysis was conducted using a random-effects model on outcomes with high heterogeneity.Results: Seven studies were included in our meta-analysis (n = 5,150). Significant differences were observed in a composite of cardiovascular death or hospitalization for worsening heart failure [RR: 0.77 (95% CI 0.68–0.87); I2 = 18%; P < 0.0001), hospitalization for worsening heart failure [RR: 0.71 (95% CI 0.61–0.82); I2 = 0%; P < 0.00001], changes in Kansas City Cardiomyopathy Questionnaire (KCCQ) score [MD: 1.70 (95% CI 1.67–1.73); I2 = 0%; P < 0.00001], and changes in body weight [MD: −1.43 (95% CI −2.15 to −0.72); I2 = 84%; P < 0.0001) from baseline. However, empagliflozin did not show a better change in the 6-min walk test (6MWT) [MD: 34.06 (95% CI −29.75–97.88); I2 = 97%; P = 0.30] or NT-proBNP [MD: −98.36 (95% CI, −225.83–29.11); I2 = 68%; P = 0.13] from baseline.Conclusion: The findings suggest that empagliflozin was effective in reducing a composite of cardiovascular death or hospitalization for worsening heart failure. Further well-designed RCTs are needed to evaluate the long-term effect of empagliflozin in patients with HF.PROSPERO: CRD42021231712.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Pan

Lin

Chen

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…The most distinctive difference between our meta-analysis and other recent ones ( 63 , 64 ) is that this is the first meta-analysis investigating all current RCTs on SGLT2 inhibitors on HF with clinical endpoints, irrespective of the size of the trial. Furthermore, we included all available data of post-hoc analyses from large trials to elaborate the safety and efficacy of SGLT2 inhibitors in patients with established HF at baseline, irrespective of their diabetes status.…”

Section: Strengths Of This Meta-analysis and Differences As Compared To Other Meta-analysesmentioning

confidence: 92%

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

Gager

Gelbenegger

Jilma

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

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.

show abstract

“… Among the binary secondary end points the statistically significant ones were KCCQ OS increase ≥ 5 points at 6 weeks, KCCQ CS increase ≥ 5 points at 12 weeks, NT pro-BNP decrease ≥20% at 12 weeks, BNP decrease ≥20% at 12 weeks. Among the continuous secondary end points the mean adjusted BNP at 12 weeks, mean adjusted KCCQ OS at 12 weeks, mean adjusted KCCQ CS at 12 weeks, mean adjusted HbA1c at 6 weeks were statistically significant IDDIA (2020) 26 60 Randomized, double-blind, placebo-controlled trial Follow up 24 weeks Patients with T2DM and HbA1c of 7.0% to 10.0% accompanied by LV diastolic dysfunction at least grade 1 (relaxation abnormality) on resting echocardiography Primary end point: Change is LV diastolic reserve at 24 weeks from baseline as assessed by diastolic stress echocardiography Secondary end points: Changes at 24 weeks in LV diastolic parameters at rest and during exercise, LV mass index, and left atrial volume index The patients in dapagliflozin group had significantly improved DR25W (0.88±1.24 cm/s versus −0.52±1.53 cm/s; P = 0.001) and DR50W (0.59±1.47 cm/s versus −0.58±1.63 cm/s; P = 0.035) compared with those in the placebo group at 24 weeks. Abbreviations: DAPA-HF, Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure; DECLARE-TIMI 58, Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes; DEFINE-HF, Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure With Reduced Ejection Fraction; IDDIA, Randomized, Controlled Trial to Evaluate the Effect of Dapagliflozin on Left Ventricular Diastolic Function in Patients With Type 2 Diabetes Mellitus; HFrEF, Heart failure with reduced ejection fraction; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro b-type natriuretic peptide; eGFR, estimated glomerular filtration rate; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; GDMT, guideline-directed medical therapy; MACE, major adverse cardiovascular events; T2DM, Type 2 Diabetes Mellitus; HF, heart failure; KCCQ, Kansas City Cardiomyopathy Questionnaire; KCCQ-OS, Kansas City Cardiomyopathy Questionnaire Overall Summary Score; HbA1c, Glycated hemoglobin; KCCQ CS, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score; BNP, B-type natriuretic peptide; LV, left ventricular; DR25W, Diastolic reserve at 25 Watts; DR50W, Diastolic reserve at 50 Watts.…”

Section: Existing Literature On Role Of Dapagliflozin In Cardiorenal Diseasementioning

confidence: 97%

The Role of Dapagliflozin in the Management of Heart Failure: An Update on the Emerging Evidence

Gupta¹,

Rao²,

Manek³

et al. 2021

TCRM

View full text Add to dashboard Cite

The burden and cost of heart failure management, primarily in the form of hospitalization in the setting of decompensated heart failure, continue to be some of the biggest clinical challenges in cardiovascular medicine. In recently published randomized controlled trials, including DAPA-HF, sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin was shown to reduce hospitalization from heart failure or mortality associated with cardiovascular causes, when added to existing guideline-directed medical therapy. The American College of Cardiology (ACC) released a Clinical Pathway guideline that recommends the use of dapagliflozin in clinical management of heart failure, with or without diabetes. Furthermore, the results of the DAPA-CKD trial broaden the utility of dapagliflozin as a therapeutic option in patients with advanced kidney disease. In this article, the authors explore the existing evidence on dapagliflozin in heart failure with reduced ejection fraction and highlight the need for further research on uses of dapagliflozin in the world of heart failure.

show abstract

Effects and safety of SGLT2 inhibitors compared to placebo in patients with heart failure: A systematic review and meta-analysis

Cited by 20 publications

References 72 publications

Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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

The Role of Dapagliflozin in the Management of Heart Failure: An Update on the Emerging Evidence

Contact Info

Product

Resources

About