Commentary: Cardiovascular Outcome in Patients Treated With SGLT2 Inhibitors for Heart Failure: A Meta-Analysis
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SUBMITTER: Qiu M
PROVIDER: S-EPMC8576193 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC8316592 | biostudies-literature
Project description:BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the composite of heart failure (HF) hospitalizations or cardiovascular mortality among patients with HF. However, the efficacy of SGLT2 inhibitors in secondary endpoints of randomized trials and in subgroups of HF patients is not well known.MethodsWe performed a systematic review and meta-analysis of placebo-controlled, randomized trials of SGLT2 inhibitors in patients with HF. PubMed, Embase, and Cochrane databases were searched for trials published up to January 21, 2021. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Hazard ratios (HRs) with 95% CI were pooled across trials. The primary endpoints of interest were all-cause and cardiovascular mortality.ResultsOut of 3969 database results, 15 randomized trials and 20,241 patients were included; 10,594 (52·3%) received SGLT2 inhibitors. All-cause mortality (HR 0·86; 95% CI 0·79-0·94; p = 0·0007; I2=0%) and cardiovascular mortality (HR 0·86; 95% CI 0·78-0·96; p = 0·006; I2=0%) were significantly lower in patients treated with SGLT2 inhibitors compared with placebo. The composite of cardiovascular mortality, HF hospitalizations, or urgent visits for HF was significantly reduced with SGLT2 inhibitors in all the following subgroups: male, female, age < 65, age ≥ 65, race - Black and White, estimated glomerular filtration rate (eGFR) <60, eGFR ≥60, New York Heart Association (NYHA) class II, NYHA ≥III, and HF with preserved ejection fraction.InterpretationIn patients with HF, SGLT2 inhibitors significantly reduce all-cause and cardiovascular mortality compared with placebo. In addition, the composite of cardiovascular mortality or HF hospitalizations/urgent visits is reduced with SGLT2 inhibitors across subgroups of sex, age, race, eGFR, HF functional class, and ejection fraction.
| S-EPMC8257984 | biostudies-literature
Project description:AimsNo studies have comprehensively compared the efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitors, renin-angiotensin system (RAS) inhibitors, and angiotensin receptor neprilysin (ARN) inhibitors based on different type of heart failure, including heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The aim of this network meta-analysis was to evaluate the relative efficacy of SGLT2 inhibitor (SGLT2i), RAS inhibitor (RASi) and ARN inhibitor (ARNI) in different types of heart failure.MethodsA systemic literature search was performed from inception to 19 November 2022 for randomized control trials assessing the risk of cardiovascular (CV) death or hospitalization for heart failure (HHF) of these drugs in HF. A network meta-analysis was performed. Risk ratio (RR) with 95% confidence intervals (CI) were synthesized.ResultsSeventeen studies were selected with a total of 61 489 patients. In patients with HFrEF, ARNI led to a reduced risk of a composite outcome of CV death or HHF when compared with placebo (RR = 0.83, 95% CI 0.77-0.89). Similar trends were observed when focusing on the outcome of CV death or HHF alone. In patients with HFpEF, SGLT2i showed the beneficial effects on the CV death or HHF events when compared with placebo and RASi (RR = 0.82, 95% CI 0.74-0.92; RR = 1.16, 95% CI 1.02-1.31). For CV death, all these three drugs could not show beneficial effects in HFpEF. For the incidence of HHF in HFpEF, both SGLT2i and ARNI demonstrated the beneficial effects but SGLT2i was superior to ARNI. There were no differences in the events of discontinuation under these drugs when compared with placebo or each other in either HFrEF or HFpEF patients. SGLT2i showed the least renal injury among these interventions in HFrEF and there were no differences in the incidence of renal injury of these interventions in HFpEF.ConclusionsAmong these drugs, ARNI showed the greatest ability to lower the incidence of CV death or HHF and SGLT2i exerted the least renal injury in patients with HFrEF. In patients with HFpEF, SGLT2i was associated with a reduction in the risk of CV death or HHF. There were no differences in the incidence of renal injury of these interventions in HFpEF. The intolerance of these drugs were comparable in both HFrEF and HFpEF.
| S-EPMC10053170 | biostudies-literature
Project description:BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors have shown promise in improving cardiovascular outcome in patients with heart failure (HF) and diabetes mellitus (DM). Although these benefits have been confirmed by several meta-analyses, small studies have not been included into these pooled analyses.AimPublication of recent RCTs prompted us to perform this updated meta-analysis to examine the consistency of favorable cardiovascular outcomes of SGLT2 inhibitors in HF patients by inclusion of clinical trials with small sample size.MethodsWe conducted a systematic review of the literature in PubMed/Medline and ClinicalTrials.gov to identify all RCTs investigating the benefits of SGLT2 inhibitors in patients with HF. The primary endpoint of this meta-analysis was to compare the cardiovascular death (CVD) and hospitalization for HF (HHF) between patients who received an SGLT2 inhibitor and those who received a placebo or a non-SGLT2 inhibitor. We used a risk difference (RD) and log hazard ratio (HR) to pool the reported difference across the included RCTs.ResultsA total of 12 RCTs encompassing 59,825 patients at different stages of HF and DM were included, 32,448 patients in the SGLT2 inhibitor group and 27,377 patients in the control group. A pooled analysis of RCTs, regardless of HF severity or DM status, showed a significantly reduced RD for CVD (RD =-0.01, 95% CI [-0.01, 0.00], P=0.01) and HHF (RD =-0.02, 95% CI [-0.03, -0.01], P=0.0005) in patients who received a SGLT2 inhibitor compared to those who did not. A sub-group analysis showed a significantly reduced RD for CVD (RD =-0.01, 95% CI [-0.02, 0.00], P=0.03) and HHF (RD =-0.02, 95% CI [-0.03, 0.00], P=0.01) in patients with DM who received SGLT2 inhibitors regardless of the severity of HF. Also, regardless of DM status, RD for HHF favored the use of SGLT2 inhibitor than the control medication (RD =-0.05, 95% CI [-0.06, -0.03], P<0.00001).ConclusionSGLT2 inhibitors have shown a promise in reducing CVD and HHF in patients with HF, regardless of ejection fraction or diabetes status.
| S-EPMC8303041 | biostudies-literature
Project description:Acute heart failure (AHF) is a major public health concern, affecting 26 million worldwide. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering drugs, comprising canagliflozin, dapagliflozin, and empagliflozin that are being explored for AHF. We aim to meta-analyze the effectiveness of SGLT2 inhibitors compared to placebo for primary outcomes including all-cause and cardiovascular mortality, heart failure events, symptomatic improvement, and readmissions. Our secondary outcome is the risk of serious adverse events. This meta-analysis has been designed in accordance with the PRISMA Statement 2020. A systematic search across PubMed, Scopus, and Cochrane Library was conducted through August 13, 2022. The following keywords were utilized: sglt2, sodium-glucose transporter 2 inhibitors, sglt2 inhibitors, decompensated heart failure, de-novo heart failure, and/or acute heart failure. Only randomized controlled trials (RCTs) with adult patients (>18 years), hospitalized with de-novo AHF, acutely decompensated chronic heart failure with reduced, borderline, or preserved ejection, and receiving SGLT2 inhibitors were included. A quantitative analytical methodology was applied where the standardized mean difference (SMD) applying 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) with 95% CI was yielded. All tests were carried out on Review Manager 5.4 (Cochrane). In total, three RCTs were included pooling in a total of 1831 patients where 49.9% received SGLT2 inhibitors. The mean age was 72.9 years in the interventional group compared to 70.6 years in the placebo. Only 33.7% of the sample was female. The follow-up spanned 2−9 months. Heart failure events were reduced by 62% in the interventional group (RR = 0.66, p < 0.0001). readmissions had a reduced risk of 24% with SGLT2 inhibitors (RR = 0.76, p = 0.03). We assessed the efficacy and safety of SGLT2 inhibitors in preventing complications post-AHF. The odds of all-cause mortality, cardiovascular mortality, heart failure events, and re-admissions rates were substantially reduced within the first 1−9 months of hospitalization.
| S-EPMC9778112 | biostudies-literature
Project description:AimsWe sought to conduct a meta-analysis regarding the safety and efficacy of sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with heart failure (HF).Methods and resultsMEDLINE, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched from their inception to November 2020 for placebo-controlled randomized controlled trials of SGLT2 inhibitors. Randomized controlled trials were selected if they reported at least one of the prespecified outcomes in patients with HF. Hazard ratios (HRs) or risk ratios and their corresponding 95% confidence intervals were pooled using a random-effects model. A total of seven trials including 16 820 HF patients (N = 8884 in the SGLT2 inhibitor arms; N = 7936 in the placebo arms) were included. In the overall HF cohort, SGLT2 inhibitors compared with placebo significantly reduced the risk of the composite endpoint of first HF hospitalization or cardiovascular death [HR: 0.77 (0.72-0.83); P < 0.001; I2 = 0%], time to first HF hospitalization [HR: 0.71 (0.64-0.78); P < 0.001; I2 = 0], cardiovascular mortality [HR: 0.87 (0.79-0.96); P = 0.005; I2 = 0%], and all-cause mortality [HR: 0.89 (0.82-0.96); P = 0.004; I2 = 0%]. Results remained consistent across HF-specific trials and according to diabetes mellitus status. A trend towards benefit was observed in patients with HF with preserved ejection fraction for the composite of HF hospitalization and cardiovascular death [HR: 0.80 (0.63-1.00); P = 0.05; I2 = 29%]. No increased risk of hypovolaemia, hyperkalaemia, and hypotension was seen with SGLT2 inhibitors compared with placebo.ConclusionsSGLT2 inhibitors significantly improve cardiovascular outcomes including cardiovascular and all-cause mortality in patients with HF without an increased risk of serious adverse events. A trend towards benefit was observed in patients with HF with preserved ejection fraction.
| S-EPMC7755023 | biostudies-literature
Project description:AimsRecent randomised controlled trials (RCTs) have shown a significant prognostic benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the cardiovascular (CV) profile of patients with diabetes. This systematic review and meta-analysis aim to provide a concise evaluation of all the available evidence for the use of these agents in patients with heart failure (HF) regardless of their baseline diabetes status.Methods and resultsPubMed, Web of Science, and Cochrane library databases were systematically searched from inception until November 20th 2020. Eight studies consisting of 13,275 patients were included in the meta-analysis. For the total population, SGLT2 inhibitors reduced the risk of all-cause mortality (HR: 0.83; 95% CI: 0.75-0.91; I 2 0%), hospitalisation for HF (HR: 0.68; 95% CI: 0.61-0.75; I 2: 0%), CV death (HR: 0.82; 95% CI: 0.74-0.92; I 2: 0%), and hospitalisation for HF or CV death (HR: 0.72; 95% CI: 0.66-0.78; I 2: 0%). Subgroup analyses of the total population according to the diabetes status showed that SGLT2 inhibitors significantly reduced the risk of hospitalisation for HF (HR: 0.68; 95% CI: 0.61, 0.75; I 2: 0%), as well as the risk of hospitalisation for HF or CV death (HR: 0.72; 95% CI: 0.66, 078; I 2: 0%) and CV death (HR: 0.82; 95% CI: 0.74, 0.91; I 2: 0%).ConclusionsThe results of this meta-analysis confirm the growing evidence in the literature of the favourable profile of SGLT2 inhibitors in cardiovascular outcomes and mortality in patients with heart failure regardless of the baseline diabetes status. This systematic review has been registered with PROSPERO (CRD42021224777).
| S-EPMC8397556 | biostudies-literature
Project description:BackgroundNo study has compared the cardiovascular outcomes for sodium-glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)-which also have cardiovascular benefits-in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction.MethodsMedicare fee-for-service data (2013-2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting.ResultsAmong HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio [HR (95% confidence interval)], 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 [0.75, 0.99]), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 [0.79, 0.93]), but not MI or stroke (HR: 1.02 [0.85, 1.22]). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 [0.61, 0.69]) but not MI or stroke (HR: 0.90 [0.79, 1.02]), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 [0.83, 0.96]), but not MI or stroke (HR: 0.97 [0.83, 1.14]). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses.ConclusionsBias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.
| S-EPMC9999503 | biostudies-literature
Project description:BackgroundHeart failure (HF) prognosis without therapy is poor, however introduction of a range of drugs has improved it. We aimed to perform a systematic review on the effects and safety of sodium-glucose transporter 2 inhibitors (SGLT2i) in HF patients.MethodsWe carried out a systematic review of randomized controlled trials (RCTs) on SGLT2i compared to placebo for HF patients. We searched in PubMed, Scopus, Web of Science and EMBASE, with no language restriction, from inception to 31 August 2020. We included nine RCTs comprising three arms (empagliflozin, dapagliflozin and placebo). Effects sizes for continuous variables were expressed as mean differences (MDs) and 95% confidence intervals (CIs). Effects sizes for dichotomous variables were expresses as risk ratio (RR) and 95% CIs. We used random-effect models with the inverse variance method. We performed subgroup meta-analyses by intervention drug and follow-up period.ResultsSGLT2i significantly reduced all-cause mortality (RR: 0.88, 95%CI 0.79-0.98, I2 = 0%), cardiovascular mortality (RR: 0.87, 95%CI 0.77-0.99, I2 = 0%), HF hospitalization (RR: 0.73, 95%CI 0.66-0.81, I2 = 0%) and emergency room visits due to HF (RR: 0.40, 95%CI 0.21-0.76, I2 = 0%), as well as composite outcomes including the previous ones. Besides, it significantly improved the score of the Kansas City Cardiomyopathy Questionnaire (KCCQ, MD: 1.70, 95%CI 1.67-1.73, I2 = 54%). SGLT2i reduced any serious adverse events, blood pressure and weight. However, it increased hematocrit and creatinine. The meta-analysis of RCTs of > 12 weeks of follow-up showed that SGTL2i significantly reduced NT-proBNP.ConclusionsSGLT2i showed to improve critical outcomes in HF patients, and it is apparently safe.
| S-EPMC7734238 | biostudies-literature
Project description:PurposeThe use of sodium-glucose-cotransporter-type-2 inhibitors (SGLT2i) was associated in previous studies with an improved vascular function in non-human experimental models. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with chronic heart failure (CHF) and type-2 diabetes mellitus (T2DM), switching from other oral hypoglycemic agents to SGLT2i in an observational study.MethodsTwenty-two consecutive outpatients with CHF and T2DM were enrolled after switching to SGLT2i therapy, and compared with 23 consecutive controls from the same registry comparable for principal clinical characteristics. In all patients, endothelial function was assessed by FMD at baseline and after 3 months of follow-up.ResultsThree months of therapy with SGLT2i were associated with a statistically significant improvement in endothelial function (19.0 ± 5.7% vs 8.5 ± 4.1%, p < 0.0001); baseline levels of FMD were comparable between groups (p n.s.). Therapy with SGLT2i was significantly associated to improved FMD levels even at multivariable stepwise regression analysis (p < 0.001).ConclusionsSwitch to SGLT2i in patients with CHF and T2DM was associated in an observational non-randomized study with an improved endothelial function.
| S-EPMC9652233 | biostudies-literature