Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects.
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SUBMITTER: Palmiero G
PROVIDER: S-EPMC8199383 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:Angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose co-transporter-2 inhibitor (SGLT2i) have shown benefits in diabetic patients with heart failure with reduced ejection fraction (HFrEF). However, their combined effect has not been revealed. We retrospectively identified diabetic patients with HFrEF who were prescribed an ARNI and/or SGLT2i. The patients were divided into groups treated with both ARNI and SGLT2i (group 1), ARNI but not SGLT2i (group 2), SGLT2i but not ARNI (group 3), and neither ARNI nor SGLT2i (group 4). After propensity score-matching, the occurrence of hospitalization for heart failure (HHF), cardiovascular mortality, and changes in echocardiographic parameters were analyzed. Of the 206 matched patients, 92 (44.7%) had to undergo HHF and 43 (20.9%) died of cardiovascular causes during a median 27.6 months of follow-up. Patients in group 1 exhibited a lower risk of HHF and cardiovascular mortality compared to those in the other groups. Improvements in the left ventricular ejection fraction and E/e' were more pronounced in group 1 than in groups 2, 3 and 4. These echocardiographic improvements were more prominent after the initiation of ARNI, compare to the initiation of SGLT2i. In diabetic patients with HFrEF, combination of ARNI and SGT2i showed significant improvement in cardiac function and prognosis. ARNI-SGLT2i combination therapy may improve the clinical course of HFrEF in diabetic patients.
| S-EPMC8595580 | biostudies-literature
Project description:AimsHeart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality. HF with preserved ejection fraction (HFpEF), or diastolic failure, accounts for half of all HF cases and differs from HF with reduced ejection fraction (HFrEF). Patients with HFpEF are typically older, female, and commonly seen with chronic kidney disease (CKD), one of the leading independent risk factors for mortality in these patients. Unfortunately, drugs that had shown significant improvements in mortality in HFrEF have not shown similar benefits in HFpEF. Recently, sodium glucose transporter 2 inhibitors (SGLT2i) have been shown to reduce cardiovascular morbidity and mortality in HFrEF patients and slow down CKD progression. This study aimed to elucidate the impact of this drug class on mortality and risk of end stage renal disease in patients with HFpEF, which is currently unclear.Methods and resultsWe retrospectively analysed the Research Data Warehouse containing electronic health records from de-identified patients (n = 1 266 290) from the University of Mississippi Medical Center from 2013 to 2022. HFpEF patients had an average follow-up of 4 ± 2 years. Factors associated with increased all-cause mortality during HFpEF included age, male sex, and CKD. Interestingly, the only treatments associated with significant improvements in survival were angiotensin converting enzyme inhibitors/angiotensin receptor blockers and SGLT2i, regardless of CKD or diabetes status. Additionally, SGLT2i use was also associated with significant decrease in the risk of end stage renal disease.ConclusionsOur results support the use of SGLT2i in an HFpEF population with relatively high rates of hypertension, CKD, and black race and suggests that improvements in mortality may be through preserving kidney function.
| S-EPMC10192275 | biostudies-literature
Project description: Not available
| S-EPMC7868098 | 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:BACKGROUND:The effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on cardiac function are not fully understood. We investigated the changes in cardiac function in diabetic patients according to the presence and types of heart failure (HF). METHODS:We retrospectively identified 202 diabetic patients who underwent echocardiography before, and 6 to 24 months after the initiation of SGLT2i. After propensity score matching with diabetic patients without SGLT2i, the study population (n?=?304) were categorized into group 1 (without HF nor SGLT2i; n?=?76), group 2 (without HF and received SGLT2i; n?=?78), group 3 (with HF but without SGLT2i; n?=?76), and group 4 (with HF and received SGLT2i; n?=?74). Changes in echocardiographic parameters were compared between these 4 groups, and between HF patients with reduced versus preserved ejection fraction (EF). RESULTS:After a median 13 months of follow-up, HF patients with SGLT2i showed a significant decrease in left ventricular end-diastolic dimension (LV-EDD; from 57.4 mm [50.0-64.9] to 53.0 mm [48.0-60.0]; p?<?0.001) and improvement in LV-EF (from 36.1% [25.6-47.5] to 45.0% [34.8-56.3]; p?<?0.001). LV mass index and diastolic parameters also showed improvements in HF patients with SGLT2i. The SGLT2i-induced improvements in cardiac function were more prominent in HF patients than those without HF, and in HFrEF patients than HFpEF patients. CONCLUSIONS:Use of SGLT2i improved cardiac function in diabetic patients, regardless of the presence of HF. The improvements were more prominent in HF patients, especially in those with HFrEF. These improvements in cardiac function would contribute to the clinical benefit of SGLT2i.
| S-EPMC7254690 | 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: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: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: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