SGLT2 Inhibitors: New Hope for the Treatment of Acute Myocardial Infarction?

Wu, Yujie; Wang, Si-Bo; Wang, Liansheng

doi:10.1007/s40256-022-00545-6

Cited by 4 publications

(5 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The study included patients with eGFR > 15 mL/min/1.73 m 2 , and the results showed that empagliflozin could delay the decline of eGFR in the enrolled patients. Clinical studies and experimental studies on SGLT2 inhibitor treatment after AMI were limited [ 32 ]. In the current study, we observed that DAPA treatment was significantly associated with a reduced risk of all-cause death in patients with AMI after PCI.…”

Section: Discussionmentioning

confidence: 99%

Association of SGLT2 inhibitor dapagliflozin with risks of acute kidney injury and all-cause mortality in acute myocardial infarction patients

Cai,

Chen,

Mao

et al. 2024

Eur J Clin Pharmacol

View full text Add to dashboard Cite

Objective Sodium-glucose cotransporter 2 (SGLT2) inhibitors have well-documented effects in reducing hospitalization or cardiovascular mortality, while the association of SGLT2 inhibitor dapagliflozin (DAPA) and the risk of acute kidney injury (AKI) in acute myocardial infarction (AMI) patients has not been comprehensively investigated. Therefore, we aimed to assess the association between DAPA and AKI risk in AMI patients after percutaneous coronary intervention (PCI) therapy. Methods Using the Changzhou Acute Myocardial Infarction Registry database, we retrospectively included AMI patients from January 2017 to August 2021 and analyzed the risk of AKI and all-cause mortality after PCI therapy. The patients were divided into two groups according to the use of DAPA (DAPA group and Ctrl group). Patients in the DAPA group started to use DAPA after admission and continued its use during hospitalization and follow-up period. Baseline characteristics were balanced between the two groups with a propensity score matching (PSM) analysis. The outcome was AKI within 7 days after PCI and all-cause mortality during a follow-up of 2 years. Univariate and multivariate logistic regression analyses were used to assess the association between DAPA and AKI risk. Results A total of 1839 AMI patients undergoing PCI were enrolled. DAPA was used in 278 (15.1%) patients. Postoperative AKI occurred in 351 (19.1%) cases. A 1:1 PSM analysis was used to reduce confounding factors. The multivariate stepwise regression analysis showed that DAPA (odds ratio, OR 0.66; 95% confidence interval, CI 0.44–0.97; P = 0.036) was an independent protective factor in the entire cohort. After matching, the use of DAPA in AMI patients was independently associated with a decline of AKI risk (OR 0.32; 95% CI, 0.19–0.53; P < 0.001) after hospital admission. Meanwhile, there were significant differences in mortality between the DAPA group and Ctrl group (2.5% vs. 7.6%, P = 0.012). Conclusion SGLT2 inhibitor DAPA was associated with lower risks of incident AKI and all-cause mortality in AMI patients after PCI therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of SGLT2 inhibitor dapagliflozin with risks of acute kidney injury and all-cause mortality in acute myocardial infarction patients

Cai,

Chen,

Mao

et al. 2024

Eur J Clin Pharmacol

View full text Add to dashboard Cite

show abstract

“…SGLT2i have shown significant promise as a cardioprotective agent in basic and clinical studies. They have been shown to reduce the risk of cardiovascular death, stroke, and non-fatal myocardial infarction, irrespective of the presence of diabetes [3][4][5][23][24][25][26][27][28] . These positive trials prompted the recommendation of these agents in patients with heart failure even in the absence of diabetes [17] .…”

Section: Discussionmentioning

confidence: 99%

Comparative effects of canagliflozin and sitagliptin in chronically ischemic myocardium

Sabe,

Harris,

Broadwin

et al. 2024

Vessel Plus

View full text Add to dashboard Cite

Aim: Recent studies demonstrate that sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i), two classes of antidiabetic drugs, are cardioprotective. However, the mechanisms of these benefits and their comparative efficacy remain unclear. We aimed to compare the effects of these antidiabetic agents on cardiac function, perfusion, and microvascular density using a swine model of chronic myocardial ischemia. Methods: Chronic myocardial ischemia was induced in Yorkshire swine by ameroid constrictor placement to the left circumflex artery. Two weeks later, pigs were administered vehicle (“CON”, 8 pigs), 300 mg SGLT2i canagliflozin, (“CANA”, 8 pigs), or 100 mg DPP4i sitagliptin (“SIT”, 5 pigs) daily. Five weeks later, pigs were euthanized. Cardiac function, perfusion, collateralization, and protein expression were determined by pressure-volume catheter, microsphere analysis, immunofluorescence, and immunoblotting, respectively. Results: Compared with SIT, CANA was associated with improved stroke volume and cardiac output, with a trend towards reduced left ventricular stiffness. Both CANA and SIT trended towards improved perfusion compared to CON, but there were no differences between the two treatment groups. SIT was associated with improved capillary density with a trend towards improved arteriolar density compared to CANA. Both CANA and SIT were associated with increased expression of vascular endothelial cadherin compared to CON, without differences in treatment groups. SIT pigs had decreased 5′ adenosine monophosphate-activated protein kinase activation compared to CON and CANA. There was a trend towards increased endothelial nitric oxide synthase activation in the SIT group compared to CON. There were no differences in activation of extracellular signal-regulated kinase 1/2 across groups. Conclusions: In the setting of chronic myocardial ischemia, canagliflozin is associated with improved cardiac function compared to sitagliptin, with similar effects on perfusion despite differences in microvascular collateralization.

show abstract

“…In the EMPA-REG OUTCOME trial, empagliflozin decreased cardiovascular mortality and HF hospitalization in patients with T2DM and a history of MI ( 3 ). At present, eight clinical investigations related to SGLT2i have been conducted in AMI patients with DM ( 9 , 39 , 40 ). Notably, three studies, specifically the EMMY study ( 41 ), SGLT2-I AMI PROTECT ( 39 , 40 ), and EMBODY ( 42 ) study, have effectively disseminated their findings.…”

Section: Discussionmentioning

confidence: 99%

“…The EMBODY study demonstrated that early SGLT2i administration might be effective in improving cardiac nerve activity without any adverse events ( 42 ). So far, the remaining five studies (EMPACT-MI, EMPRESS MI, DAPA-MI, NCT03658031, and NCT03591991) have not yet been published ( 9 , 43 ). These studies did not explore the cellular-level mechanisms throughout their investigations, while our research endeavors to study the impact of SGLT2i on the structural aspects of the cardiac domain within the Asian population.…”

Section: Discussionmentioning

confidence: 99%

“…The emergence of substantial cardiovascular outcome clinical trials investigating SGLT2i, such as empagliflozin (EMPA-REG OUTCOME) ( 3 ), dapagliflozin (DECLARE-TIMI 58) ( 4 ), canagliflozin (CANVAS Program) ( 5 ), ertugliflozin (VERTIS CV) ( 6 ), and sotagliflozin (SCORED) ( 7 ), has demonstrated the effects of SGLT2i on the reduction of the occurrence of cardiovascular events and hospitalization for heart failure (HF) in T2DM patients with high risks for CVD or chronic kidney disease (CKD). From the angle of underlying mechanisms, long-term exposure to hyperglycemia affected signaling pathways inducing electrical disturbances in cardiomyocytes and mitochondrial dysfunction, prompting elevated reactive oxygen species (ROS) production and even apoptosis ( 8 , 9 ). Preclinical data demonstrated ( 10 , 11 ) that SGLT2i inhibit Na + /hydrogen exchanger 1 (NHE-1), leading to a reduction of Na + in cardiac cytoplasm whose high expression was considered as a denominator of diabetes and HF and increasing Ca 2+ level in cardiac mitochondria to improve ATP generation and viability of cardiomyocytes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influence and mechanism of sodium-glucose cotransporter-2 inhibitors on the cardiac function: study protocol for a prospective cohort study

Cao

Shi

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundAcute myocardial infarction (AMI) poses a significant threat to cardiovascular diseases (CVDs), leading to a high risk of heart failure (HF) and cardiovascular death. Growing evidence has unveiled the potential of sodium-glucose cotransporter-2 (SGLT2) inhibitors to improve cardiovascular outcomes in patients with CVD regardless of diabetes, but there is limited evidence in AMI patients. Furthermore, it is controversial whether the effects can be ascribed to the amelioration of left ventricular (LV) function, which further complicates the understanding of their underlying mechanism.MethodsThis study is a prospective, phase IV, open-label, parallel group, single-center trial conducted in a large tertiary teaching hospital in China. A total of 120 patients with AMI and type 2 diabetes mellitus (T2DM) will be included. Those who received SGLT2 inhibitors are considered as the experimental group, and those taking other antidiabetic agents are considered as the control group. The primary outcome is change in LV end-systolic volume index (LVESVi) measured by cardiac magnetic resonance (CMR) imaging from baseline during 1-year follow-up period. Secondary outcomes include other LV parameters such as LV mass, LV volume, and LV ejection fraction (EF); quality of life and functional capacity such as Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS) and EuroQol-5 dimension (EQ-5D); biomarkers associated with diagnostic parameters of AMI and possible mechanisms on cardiovascular protection, such as creatine kinase, troponin T (TnT) level, troponin I (TnI) level, soluble suppression of tumorigenicity-2 (sST2), galectin-3 (Gal-3), fibroblast growth factor 21 (FGF21), and microRNA (miRNA) level.DiscussionThis study aims to investigate whether SGLT2 inhibitors could improve LV function by measuring CMR, quality of life, and functional capacity in patients with AMI in real-world settings, providing evidence on the underlying mechanism of SGLT2 inhibitors on cardioprotection.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=173672, identifier ChiCTR2200065792.

show abstract

SGLT2 Inhibitors: New Hope for the Treatment of Acute Myocardial Infarction?

Cited by 4 publications

References 103 publications

Association of SGLT2 inhibitor dapagliflozin with risks of acute kidney injury and all-cause mortality in acute myocardial infarction patients

Association of SGLT2 inhibitor dapagliflozin with risks of acute kidney injury and all-cause mortality in acute myocardial infarction patients

Comparative effects of canagliflozin and sitagliptin in chronically ischemic myocardium

Influence and mechanism of sodium-glucose cotransporter-2 inhibitors on the cardiac function: study protocol for a prospective cohort study

Contact Info

Product

Resources

About