Sodium–glucose cotransporter-2 Inhibitors in Heart Failure: An Updated Systematic Review and Meta-analysis of 13 Randomized Clinical Trials Including 14,618 Patients With Heart Failure

Shrestha, Dhan Bahadur; Budhathoki, Pravash; Sedhai, Yub Raj; Karki, Parag; Gurung, Suja; Raut, Sumit; Damonte, Juan Ignacio; Del, Marco Giuseppe; Mojadidi, Mohammad K.; Elgendy, Islam Y.; Patel, Toralben; Patel, Nimesh

doi:10.1097/fjc.0000000000001099

Cited by 13 publications

(6 citation statements)

References 34 publications

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“…In previous meta-analysis, adverse events were similar between SGLT2 inhibitors and placebo, except for a mild increase in genital infection in the SGLT2 subgroup. This is concordant with the reassuring safety information regarding SGLT2 inhibitors' use during the hospitalization [75][76][77]. Taking all this data into account, we could hypothesize that the relative benefit of SGLT2 inhibitors on HF outcomes remains constant regardless of target population.…”

Section: Practical Management: When To Start Sglt2 Inhibitors During ...supporting

confidence: 78%

Sodium-glucose Co-transporter 2 Inhibitors in Acute Heart Failure: A Review of the Available Evidence and Practical Guidance on Clinical Use

Morillas¹,

Galcerá²,

Alania³

et al. 2022

Rev. Cardiovasc. Med.

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Sodium-glucose co-transporter 2 (SGLT2) inhibitors were initially conceived as glucose-lowering agents. However, striking renal and cardiovascular benefits were observed in type 2 diabetes trials. This led to evaluate it in dedicated studies in chronic heart failure (HF) and chronic kidney disease, which also showed remarkable clinical results. Given this findings, and taking into account the multiple mechanisms of action, the use of SGLT2 inhibitors in acute heart failure seemed promising. Sotagliflozin was the first SGLT2 inhibitor to reduce heart failure hospitalizations within the acute setting in the SOLOIST-WHF trial. Only type 2 diabetes patients were included, with a preserved and reduced ejection fraction. In slightly less than half of the cohort, this medication was started when the diuretic therapy was transitioned from intravenous to oral, during the hospital admission. In the rest of the patients, sotagliflozin was started early after discharge. Empagliflozin proved to be safe, well-tolerated, increased diuresis, and reduced a combined clinical endpoint (worsening HF, rehospitalization for HF, or death at 60 days) when administered within the first 24 hours of an acute heart failure hospitalization in the EMPA-RESPONSE-AHF trial. More recently, empagliflozin showed a reduction in a composite primary endpoint of death, heart failure events, and quality of life compared to placebo in the EMPULSE trial. Empagliflozin was started after the initial stabilization phase, but while patients were still admitted and receiving intravenous loop diuretics. Less than half of the patients were diabetic and two-thirds had a left ventricular ejection fraction below 40%. Dapagliflozin is currently being tested in the DAPA ACT HF-TIMI 68 trial, which plans to enroll 2400 patients admitted with acute heart failure and reduced ejection fraction. We envision SGLT2 inhibitors as a useful tool in acute heart failure syndrome given the additive diuretic effect, and minimal impact on blood pressure, kidney function, and electrolytes. Its dosage schedule is simple and can help initiation and tolerance of other medical therapy. However, there is an increased risk of genital infections and euglycaemic ketoacidosis. Notwithstanding, once critically ill and fasting patients are excluded, early administration of SGLT2 inhibitors is safe. This review summarizes the development of SGLT2 inhibitors and the available evidence supporting their use during an acute heart failure admission. We also propose a practical guideline for in-hospital initiation and monitoring.

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Section: Practical Management: When To Start Sglt2 Inhibitors During ...supporting

confidence: 78%

Sodium-glucose Co-transporter 2 Inhibitors in Acute Heart Failure: A Review of the Available Evidence and Practical Guidance on Clinical Use

Morillas¹,

Galcerá²,

Alania³

et al. 2022

Rev. Cardiovasc. Med.

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“…Marfella et al, The accumulated evidence from these studies highlights the therapeutic potential of SGLT2 inhibitors, particularly Empagliflozin, in the management of AHF. It is worth noting that the beneficial effects of these drugs appear to extend beyond their initial purpose as glucose-lowering agents in T2DM [20][21][22]. These studies suggest an additional cardioprotective effect, translating into improved patient outcomes, a notion supported by the current literature [23][24][25][26].…”

Section: Discussionmentioning

confidence: 70%

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors for Acute Heart Failure: A Systematic Review

Imtiaz,

Eshete,

Arshad

et al. 2024

JAMMR

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Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have recently drawn attention as a viable therapy for acute heart failure (AHF). Despite this, a comprehensive synthesis of current research has not been undertaken. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this systematic review evaluated eight studies involving 3,352 participants. The scope encompassed research from the last twenty years, focusing on the effectiveness of SGLT2 inhibitors in AHF management. Detailed considerations regarding the temporal context and heterogeneity were incorporated into the methodology. Results: The utilization of SGLT2 inhibitors yielded compelling results in improving cardiovascular outcomes, showcasing a substantial 58.2% reduction in major adverse cardiovascular events (MACE) and a noteworthy 15% decrease in NT-proBNP levels. Empagliflozin therapy, specifically, exhibited enhanced clinical efficacy, as indicated by a 48% improvement in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score. Furthermore, a detailed analysis revealed that markers of acute kidney injury witnessed a significant reduction after the administration of empagliflozin. This reduction reached statistical significance after 3 days of treatment (P=0.02) and persisted through the 7-day assessment (P=0.003). This comprehensive exploration of the results provides a more nuanced understanding of the multifaceted benefits associated with SGLT2 inhibitors, particularly empagliflozin, in the management of acute heart failure. Conclusion: The current body of research strongly supports the application of SGLT2 inhibitors in managing AHF, emphasizing considerable improvements in clinical outcomes. Despite these positive findings, the abstract acknowledges the need for further research to determine the optimal timing, dosage, long-term safety of these inhibitors, and their effectiveness across diverse patient populations.

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“…Subgroup analysis showed no significant associations between SGLT2i and SBP in terms of baseline characteristics, baseline anti-HF drugs administered, or type of study. A meta-analysis indicated that SGLT2i improved cardiovascular outcomes and that the clinical benefit was comparable between diabetic and nondiabetic individuals, men and women, and younger and older patients with underlying HF [ 55 ]. Further research is needed to identify the most suitable populations for SGLT2i.…”

Section: Discussionmentioning

confidence: 99%

Effect of sodium-glucose cotransporter-2 inhibitors on blood pressure in patients with heart failure: a systematic review and meta-analysis

Fan

et al. 2022

Cardiovasc Diabetol

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Background Recent studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) can achieve significant improvement in blood pressure in people with diabetes. Furthermore, randomized controlled trials (RCTs) have established that SGLT2i have a cardioprotective effect in adults with heart failure (HF). Therefore, we performed this systematic review an meta-analysis to determine the effect of SGLT2i on blood pressure in patients with HF. Methods We used the Medline, Cochrane Library, Embase, and PubMed databases to identify RCTs (published through to April 29, 2022) that evaluated the effect of SGLT2i on HF. The primary endpoint was defined as change in blood pressure. Secondary composite outcomes were heart rate, hematocrit, body weight, and glycated hemoglobin. The N-terminal pro-brain natriuretic peptide level, Kansas City Cardiomyopathy Questionnaire scores, and estimated glomerular filtration rate were also evaluated. Results After a literature search and detailed evaluation, 16 RCTs were included in the quantitative analysis. Pooled analyses showed that SGLT2i were associated with a statistically significant reduction in systolic blood pressure of 1.68 mmHg (95% confidence interval [CI] − 2.7, − 0.66; P = 0.001; I2 = 45%) but not diastolic blood pressure (mean difference [MD] −1.06 mmHg; 95% CI −3.20, 1.08; P = 0.33; I2 = 43%) in comparison with controls. Furthermore, SGLT2i decreased body weight (MD − 1.36 kg, 95% CI − 1.68, − 1.03; P < 0.001; I2 = 61%) and the glycated hemoglobin level (MD − 0.16%, 95% CI − 0.28, −0.04, P = 0.007; I2 = 91%) but increased hematocrit (MD 1.63%, 95% CI 0.63, 2.62, P = 0.001; I2 = 100%). There was no significant between-group difference in heart rate (MD − 0.35; 95% CI − 2.05, 1.35, P = 0.69; I2 = 0). Conclusions SGLT2i decreased systolic blood pressure in patients with HF but had no effect on diastolic blood pressure. These inhibitors may have numerous potentially beneficial clinical effects in patients with HF.

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Sodium–glucose cotransporter-2 Inhibitors in Heart Failure: An Updated Systematic Review and Meta-analysis of 13 Randomized Clinical Trials Including 14,618 Patients With Heart Failure

Cited by 13 publications

References 34 publications

Sodium-glucose Co-transporter 2 Inhibitors in Acute Heart Failure: A Review of the Available Evidence and Practical Guidance on Clinical Use

Sodium-glucose Co-transporter 2 Inhibitors in Acute Heart Failure: A Review of the Available Evidence and Practical Guidance on Clinical Use

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors for Acute Heart Failure: A Systematic Review

Effect of sodium-glucose cotransporter-2 inhibitors on blood pressure in patients with heart failure: a systematic review and meta-analysis

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