Despite the robust clinical evidence base supporting their role for high-risk patients with type 2 diabetes (T2DM) and concomitant cardiovascular disease, prescription of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) remains suboptimal. Clinical encounters occurring in the period post angiography may present a key opportunity to improve implementation in high-risk patients with T2DM.

Reminders EMbedded IN PCI Reports to Optimize Discharge Diabetes Mellitus Care (REMIND-DM) is a pragmatic, prospective, cluster randomized quality improvement study in patients with type 2 diabetes undergoing angiography and was run as a quality improvement initiative. Following a 6 month "baseline period", REMIND-DM randomized 23 participating percutaneous coronary intervention (PCI) sites (caring for 7,045 patients over the study period) within the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) quality improvement collaborative to either usual care or a quality improvement intervention consisting of a templated PCI report "reminder" of medication eligibility linked to a decision support tool. Sites were followed for a 6 month "evaluation period." The primary outcome is the new prescription of SGLT2 inhibitor or GLP-1RA among eligible patients at discharge after PCI. To examine the effectiveness of the intervention, primary analyses will be conducted using a difference-in-difference design examining changes in new cardioprotective therapy prescription from baseline to the evaluation periods in both arms.

The REMIND-DM implementation trial has enrolled a large, high-risk population of patients with T2DM and will determine the effectiveness of a low touch QI intervention within BMC2 implemented in the post-PCI period to improve timely prescription of risk lowering therapies in high-risk patients with T2DM.

To identify pharmacological randomized controlled trials (RCTs) with "positive" outcomes driven by nonfatal myocardial infarction (MI) reductions and assess related guideline recommendations.

RCTs published between 2000 and 2024 focusing on mortality and nonfatal MI were identified through searches in PubMed and Web of Science. Citation tracking was used to find trials referenced in clinical guidelines. The levels of guideline recommendations based on the supporting trials were summarized. The impact of nonfatal MI on composite outcomes was assessed by using the leave-one-out method.

Of 21,005 records, 6 RCTs demonstrating positive outcomes due to nonfatal MI reduction were cited in current guidelines, including anti-thrombotic (3), intensive lipid-lowering (2), and anti-inflammatory (1) therapies. Intensive lipid-lowering trials (IMPROVE-IT, FOURIER; totaling 60 recommendations across 17 guidelines) were more frequently recommended in guidelines: 45% Class I, 33.3% Class IIa, and 21.7% Class IIb. Anti-thrombotic and anti-inflammatory trials had no Class I recommendations and higher Class IIb recommendations (66.7% and 100%). A meta-analysis including major intensive lipid-lowering RCTs on top of maximally tolerated statins (IMPROVE-IT, FOURIER, and ODYSSEY OUTCOMES) revealed no statistical difference in primary composite outcome after removing nonfatal MI events (relative risk 0.94, 95% confidence interval: 0.88 to 1.01).

In contemporary pharmacological RCTs with positive composite outcome driven by nonfatal MI reduction, intensive lipid-lowering trials are more frequently received strong guideline recommendations. This analysis underscores the need to evaluate whether these recommendations fully reflect the clinical significance of the observed benefits.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent one of the main cornerstones of heart failure treatment. Nevertheless, while the cardiovascular beneficial effects of these drugs have been clearly demonstrated by several clinical trials, in clinical practice, it remains challenging to identify the appropriate timing to start SGLT2 inhibitors. The potential risk of side effects, like genito-urinary infections and interaction with other drugs, may often lead to delay the prescription of these drugs in the acute setting. However, several studies have demonstrated the safety and the prognostic impact of SGLT2 inhibitors in the hospitalized patient, suggesting that treatment initiation during hospitalization or early post-discharge may represent an ideal therapeutic option. In this review, we discuss the main trials on early administration of SGLT2 inhibitors in acute heart failure supporting early introduction of SGLT2 inhibitors to optimize heart failure treatment. The efficacy and safety of these drugs in patients with acute myocardial infarction are also discussed. Based on the review of existing evidences, a practical flowchart on early administration of SGLT2 inhibitors in the acute setting is proposed.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are oral antidiabetic agents that have shown significant improvements in cardiovascular and renal outcomes among patients with heart failure (HF), regardless of diabetic status, establishing them as a cornerstone therapy. In addition to glycemic control and the osmotic diuretic effect, the inhibition of SGLT2 improves endothelial function and vasodilation, optimizing myocardial energy metabolism and preserving cardiac contractility. Moreover, SGLT2 inhibitors may exhibit anti-inflammatory properties and attenuate acute myocardial ischemia/reperfusion injury, thereby reducing cardiac infarct size, enhancing left ventricular function, and mitigating arrhythmias. These pleiotropic effects have demonstrated efficacy across various cardiovascular conditions, ranging from acute to chronic coronary syndromes and extending to arrhythmias, valvular heart disease, cardiomyopathies, cardio-oncology, and cerebrovascular disease. This review provides an overview of the current literature on the potential mechanisms underlying the effectiveness of SGLT2 inhibitors across a wide range of cardiovascular diseases beyond HF.

Patients with type 2 diabetes, but also older patients with type 1 diabetes, are at major risk of cardiovascular morbidity and death. After an acute cardiac event, the prognosis of patients with diabetes is impaired, with clear increases in in-hospital and long-term morbidity and deaths. Both hyper- and hypoglycaemia are deleterious after an acute cardiac event, and the decision to start intravenous insulin is often challenging. Moreover, some antidiabetic treatments have cardioprotective effects, and the onset of an acute cardiac event provides an opportunity to shift to these treatments. The objective of this position statement is to offer practical tools to cardiologists seeking to improve the care of patients with diabetes hospitalized for an acute cardiac event, and to optimize collaboration between cardiologists and diabetologists. After a summary of the evidence for antidiabetic treatments in patients with acute cardiac events, we propose an algorithm to start and adapt intravenous insulin in the most severe patients, and conclude with standard insulin protocols or oral treatments at discharge. We also discuss appropriate antidiabetic treatment of these patients at discharge, based on the main cardiological diagnosis, kidney function and antidiabetic strategies. Finally, situations in which the diabetologist must be consulted are discussed.

This article reviews noteworthy additions to the literature for the management of critically ill cardiothoracic surgical patients published in 2024. We reviewed 8100 articles to identify 10 publications that provided new or updated information across a diverse range of topics including extracorporeal membrane oxygenation (ECMO), sepsis and shock, and acute hypoxemic respiratory failure (AHRF). Additional topics within these publications included prophylaxis guidelines and evidence for prevention of common complications in the intensive care unit, such as bleeding, thrombosis, and acute kidney injury (AKI).

Patients with type 2 diabetes, but also older patients with type 1 diabetes, are at major risk of cardiovascular morbidity and death. After an acute cardiac event, the prognosis of patients with diabetes is impaired, with clear increases in in-hospital and long-term morbidity and deaths. Both hyper- and hypoglycaemia are deleterious after an acute cardiac event, and the decision to start intravenous insulin is often challenging. Moreover, some antidiabetic treatments have cardioprotective effects, and the onset of an acute cardiac event provides an opportunity to shift to these treatments. The objective of this position statement is to offer practical tools to cardiologists seeking to improve the care of patients with diabetes hospitalized for an acute cardiac event, and to optimize collaboration between cardiologists and diabetologists. After a summary of the evidence for antidiabetic treatments in patients with acute cardiac events, we propose an algorithm to start and adapt intravenous insulin in the most severe patients, and conclude with standard insulin protocols or oral treatments at discharge. We also discuss appropriate antidiabetic treatment of these patients at discharge, based on the main cardiological diagnosis, kidney function and antidiabetic strategies. Finally, situations in which the diabetologist must be consulted are discussed.

Individuals with heart failure (HF), other forms of cardiovascular disease, or kidney disease are at increased risk for the development and adverse health effects of diabetes. As such, prevention or delay of diabetes is an important treatment priority in these groups. The aim of this meta-analysis was to determine the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on incident diabetes in HF across the spectrum of left ventricular ejection fraction (LVEF) and across the broader spectrum of cardiovascular or kidney disease.

First, the effects of dapagliflozin vs. placebo on new-onset diabetes were assessed in a pooled, participant-level analysis of the DAPA-HF and DELIVER trials. New-onset diabetes was defined as the new initiation of glucose-lowering therapy during follow-up, and time from randomization to new-onset diabetes was evaluated using Cox proportional hazards models. Second, PubMed and Embase were searched to identify large-scale randomized clinical outcomes trials (RCTs) comparing SGLT2i with placebo among adults with cardiovascular or kidney disease. A trial-level meta-analysis was then conducted to summarize the treatment effects of SGLT2i on the incidence of new-onset diabetes.

In the pooled analysis of DAPA-HF and DELIVER including 5623 participants with HF but without diabetes at baseline, dapagliflozin reduced the incidence of new-onset diabetes by 33% [hazard ratio (HR), 0.67; 95% confidence interval (CI), .49-.91; P = .012] when compared with placebo. There was no evidence of heterogeneity across the spectrum of continuous LVEF or key subgroups. Among seven complementary RCTs including 17 855 participants with cardiovascular or kidney disease, SGLT2i reduced the of new-onset diabetes by 26% (HR, 0.74; 95% CI .65-.85; P < .001), with consistent effects across trials.

SGLT2i reduced the incidence of new-onset diabetes among individuals with cardiovascular or kidney disease. These findings suggest that SGLT2i implementation may have an important ancillary benefit on prevention or delay of diabetes in these high-risk populations.

Ischemic heart disease (IHD) is the leading global cause of death, affecting millions and leading to significant morbidity and mortality. Ischemic cardiomyopathy (ICM), a manifestation of IHD, results in severe left ventricular dysfunction due to coronary artery disease and poses a significant challenge due to the complex pathophysiology, variable clinical presentation, and overall poor prognosis. Recent advances in medical therapy, device interventions, and revascularization techniques offer newfound hope in improving ICM patient outcomes. This article reviews the state-of-the-art management approaches for ICM, emphasizing the importance of personalized treatment plans that integrate the various contemporary therapies to address the multiple mechanisms of disease development and progression. A meticulously tailored treatment approach for each individual patient offers the hope of prolonged survival through the synergy of therapies designed to address the different and complex mechanisms that contribute to their disease process.

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Sodium-glucose co-transporter (SGLT)-2 inhibitors have shown consistent benefit in improving heart failure-related outcomes but not ischaemic cardiovascular events such as myocardial infarction or stroke. We assessed if the dual SGLT1/2 inhibitor sotagliflozin improves ischaemic outcomes.

We did a prespecified secondary analysis of the SCORED trial, which was a double-blind, placebo-controlled, randomised clinical trial enrolling patients (aged ≥18 years) with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate [eGFR] 25-60 mL/min per 1·73 m2), and additional cardiovascular risk factors. Patients at 750 sites in 44 countries were randomly assigned (1:1) to oral sotagliflozin or placebo via an interactive response technology system (block size of four; stratified by heart failure-related criteria and geographical region), with participants, investigators, and study staff, including those who assessed outcomes, masked to group assignment. Sotagliflozin treatment was prescribed at 200 mg once a day, with the dose increased to 400 mg once a day within the first 6 months if tolerated. Matching placebo was prescribed at the same treatment frequency as the intervention regimen. A prespecified secondary outcome was total major adverse cardiovascular events (MACE), which was defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, assessed as first and subsequent events. Other outcomes included total myocardial infarction and total stroke (fatal and non-fatal events) as individual post-hoc endpoints. Outcomes were assessed by intention to treat with competing-risk proportional hazard models in the overall population, and, for total MACE, in prespecified subgroups stratified by baseline demographic and clinical features (sex, age, geographical region, heart failure-related criteria, eGFR, urine albumin-creatinine ratio, and cardiovascular disease history). The SCORED trial was registered at ClinicalTrials.gov, NCT03315143, and was ended early due to loss of funding.

10 584 patients were enrolled and randomly assigned to sotagliflozin (n=5292 [50·0%]) or placebo (n=5292 [50·0%]) between Dec 8, 2017 and Jan 20, 2020 (median age 69 years [IQR 63-74]; 4754 [44·9%] female patients and 5830 [55·1%] male patients). 5144 (48·6%) patients had a history of cardiovascular disease, of whom 2108 (19·9% of the total population) had a history of myocardial infarction, 946 (8·9%) had a history of stroke, and 2375 (22·4%) had a history of coronary revascularisation. Patients in the sotagliflozin group had a significantly lower rate of total MACE than those in the placebo group (4·8 events per 100 person-years vs 6·3 events per 100 person-years; hazard ratio [HR] 0·77 [95% CI 0·65-0·91]; p=0·0020). Interaction analyses suggested a consistent effect of sotagliflozin on total MACE among stratified subgroups without evidence of heterogeneity. Additionally, sotagliflozin significantly reduced the rate of myocardial infarction (1·8 events per 100 person-years vs 2·7 events per 100 person-years; HR 0·68 [0·52-0·89]; p=0·0041) and stroke (1·2 events per 100 person-years vs 1·8 events per 100 person-years; HR 0·66 [0·48-0·91]; p=0·012) compared with placebo.

Sotagliflozin reduced MACE, with independent reductions in myocardial infarction and stroke, among patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk. The ischaemic benefit on both myocardial infarction and stroke has not been previously observed with other SGLT inhibitors and warrants investigation of combined SGLT1 and SGLT2 inhibition as a possible underlying mechanism.

Lexicon Pharmaceuticals.

Ischemic heart disease, including previous myocardial infarction (MI), is one of the main causes for the development and progression of heart failure (HF). The presence of HF before MI or the development of HF in the setting of acute coronary catastrophe is an extremely unfavorable prognostic factor leading to a multiple increase in the risk of death and rehospitalization due to HF in the post-infarction period. In 2024, the results of two randomized clinical trials (RCTs) (DAPA-MI and EMPACT-MI) were published, which assessed the effect of sodium-glucose co-transporter type 2 inhibitors (SGLT2i) on clinical outcomes in patients with acute MI. In both studies, the predetermined primary composite endpoint was not achieved. At the same time, it was shown that SGLT2i significantly reduced the risk of hospitalization for HF (empagliflozin) and contributed to the improvement of metabolic outcomes (dapagliflozin). Also, the safety of early initiation of SGLT2i in the acute period of MI was demonstrated. Based on the available results of randomized and observational clinical studies, the working group has substantiated the need for implementing these RCT results into clinical practice and proposed an algorithm for administering SGLT2 to patients with acute MI. Thus, in the presence of compelling anamnestic criteria for the diagnosis or previously diagnosed type 2 diabetes mellitus, and/or chronic kidney disease, and/or HF, continuation or timely initiation of SGLT2i during the hospitalization for index MI is recommended to improve cardiovascular and renal outcomes. Based on the results of RCTs in patients with acute MI and taking into account individual risk factors for the development of HF, the initiation of SGLT2i before discharge may be considered in order to reduce the risk of hospitalization for HF.

SGLT-2 inhibitors, initially developed for type 2 diabetes, demonstrate profound cardiorenal and metabolic benefits. This review synthesizes evidence from clinical trials and mechanistic studies to elucidate their roles in cardiovascular diseases, chronic kidney disease, and non-alcoholic fatty liver disease. Key findings include a notable reduction in cardiovascular death/heart failure hospitalization, a marked decrease in heart failure hospitalization risk, and significant improvements in renal and hepatic outcomes. Emerging mechanisms, such as autophagy induction, ketone utilization, and anti-inflammatory effects, underpin these benefits. Ongoing trials explore their potential in non-diabetic populations, positioning SGLT-2 inhibitors as transformative agents in multisystem disease management.

Left ventricular (LV) dysfunction following acute myocardial infarction (AMI) is common even in the absence of signs and symptoms of heart failure (HF). Recent trials of patients with LV dysfunction post-AMI have demonstrated low event rates during follow-up. We aimed to assess the real-world prevalence and outcomes post-AMI, stratified by LV ejection fraction (LVEF) and the presence or absence of HF symptoms.

Cohort study of patients with AMI registered in the Norwegian Myocardial Infarction Registry 2013-2022. Outcomes were short- and long-term all-cause mortality. Mortality was assessed by Kaplan-Meier survival curves, Life Table and multivariable Cox regression models.

Among 70 809 AMI patients (mean age 68.1 ± 12.9 years, 31% female), preserved (≥50%), mildly reduced (41%-49%) and reduced (≤40%) LVEF were present in 63.5%, 23.2% and 13.3%, respectively. Symptomatic HF was present in 3.3%, 28.1% and 63.2% of patients with preserved, mildly reduced and reduced LVEF. For each LVEF category, 1-year cumulative mortality rate from discharge was 3.9%, 7.8% and 17.8% for asymptomatic, and 16.2%, 13.7% and 20.2% for symptomatic patients, respectively. Symptomatic patients discharged alive had higher risk of mortality than asymptomatic: adjusted hazard ratio 1.85 (1.70-2.02) for preserved LVEF, 1.33 (1.25-1.41) for mildly reduced LVEF and 1.15 (1.06-1.24) for reduced LVEF.

Reduced LVEF in the acute phase of AMI was associated with up to 20% 1-year mortality after discharge, substantially higher than in recent post-MI trials. Symptoms of HF during the index hospitalization were associated with worse outcomes in patients with preserved LVEF but contributed little additive risk for patients with reduced LVEF.

Patients with a reduced left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) are considered to be at risk of progressive adverse cardiac remodelling which can lead to the development of heart failure and death. The early addition of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to standard treatment may delay or prevent progressive adverse remodelling in these patients.

We performed a randomized, double-blind, placebo-controlled, multicentre trial using cardiovascular magnetic resonance imaging (MRI), in patients with left ventricular systolic dysfunction following MI. Eligible patients were those ≥12 h and ≤14 days following acute MI, with an LVEF <45% by MRI. Patients were randomized to empagliflozin 10 mg once a day or matching placebo. The primary outcome was the change in left ventricular end-systolic volume indexed to body surface area (LVESVI) from baseline to 24 weeks. Secondary outcomes included measures of left ventricular and atrial volumes, left ventricular mass, LVEF, and high-sensitivity troponin I (hs-TnI) and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) concentrations. From October 2022 to January 2024, 105 eligible patients were randomized. The mean age was 63 ± 11 years and 90 (87%) were male. The mean LVEF was 34.8 ± 6.0%. In the placebo group, LVESVI decreased by 7.8 ± 16.3 ml/m2, left ventricular end-diastolic volume index (LVEDVI) did not change (-0.3 ± 18.7 ml/m2) and LVEF increased by 8.5 ± 7.4% at 24 weeks from baseline. Empagliflozin did not affect the change in LVESVI from baseline to 24 weeks (between-group difference = 0.3 ml/m2, 95% confidence interval -5.2 to 5.8; p = 0.92). Compared with placebo, empagliflozin also had no effect on LVEDVI, LVEF, left atrial volume index, left ventricular mass index, NT-proBNP, or hs-TnI, but did increase haematocrit and reduced uric acid and weight.

In patients with left ventricular systolic dysfunction after an acute MI receiving contemporary standard of care, treatment with empagliflozin had no effect on cardiac volumes or LVEF compared with placebo. Progressive adverse cardiac remodelling did not occur in the majority of patients.

The temporal changes in clinical profiles and outcomes of high-risk myocardial infarction survivors enrolled in clinical trials are poorly described. This study compares mortality rates, baseline characteristics, and the prognostic impact of therapies among participants of the VALIANT and PARADISE-MI trials.

Exclusively VALIANT participants who matched the inclusion criteria of the PARADISE-MI trial were included in the analysis. Risk of death was compared between trials using Cox regression models. The impact of baseline characteristics and therapies on mortality was estimated by the magnitude reduction of β coefficients using Cox proportional hazards regression models. A total of 9617 VALIANT participants matched the inclusion criteria of the PARADISE-MI trial (n = 5661). All-cause mortality in PARADISE-MI was less than half that in VALIANT (4.2 vs 9.9 per 100 patient-years; hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.37-0.46). This difference was reduced after adjustment for clinical variables but remained substantial (adjusted HR 0.68, 95% CI 0.58-0.80). The most important mediator of this reduction related to covariate adjustment was the use of percutaneous coronary intervention (PCI), accounting for almost half of the attenuation observed. Similar results were found for cardiovascular (CV) death, while no between-trial significant differences were found in the non-CV mortality risk.

Cardiovascular mortality following high-risk myocardial infarction has significantly declined over time, while the risk for non-CV death has remained unchanged. This improvement is partially attributable to advancements in CV care, particularly the use of PCI. Continued efforts to implement guidelines and standardize the quality of care are needed to sustain this positive trend.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to improve cardiovascular outcomes in individuals with heart failure (HF), type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, their efficacy following myocardial infarction (MI) remains unclear.

A systematic search was conducted using PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov. Primary outcomes included hospitalization for heart failure (HHF), cardiovascular (CV) death, a composite of HHF or CV death, all-cause death, major cardiovascular events (MACE), recurrent MI, severe arrhythmia, renal injury and stroke. Secondary outcomes targeted improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV).

Thirteen studies comprising 22 370 patients were included. Meta-analysis revealed that SGLT2 inhibitors reduced HHF (RR 0.69, 95% CI 0.61 to 0.78, p < 0.001), combined HHF or CV death (RR 0.87, 95% CI 0.77 to 0.99, p = 0.028), all-cause mortality (RR 0.82, 95% CI 0.73 to 0.93, p = 0.002), MACE (RR 0.68, 95% CI 0.53 to 0.88, p = 0.004), recurrent MI (RR 0.81, 95% CI 0.69 to 0.94, p = 0.007), severe arrhythmia (RR 0.54, 95% CI 0.34 to 0.85, p = 0.009) and renal injury (RR 0.68, 95% CI 0.53 to 0.87, p = 0.002). Improvement in LVEF (MD 3.96%, 95% CI 2.52 to 5.40; p < 0.001) and LVEDV (MD -5.52 mL, 95% CI -10.21 to -0.83; p = 0.021) was notably greater in the SGLT2 inhibitors group.

In post-MI patients, we first found that SGLT2 inhibitors significantly lowered the risk of HHF, combined CV death or HHF, all-cause death, MACE, recurrent MI, severe arrhythmias and renal injury. Additionally, SGLT2 inhibitors improved LVEF and LVEDV.

In the EMPACT-MI trial, empagliflozin reduced heart failure (HF) hospitalizations but not mortality in acute myocardial infarction (MI). Contemporary reports of clinical event rates with and without type 2 diabetes mellitus (T2DM) in acute MI trials are sparse. The treatment effect of empagliflozin in those with and without T2DM in acute MI is unknown.

A total of 6522 patients with acute MI with newly reduced left ventricular ejection fraction (LVEF) to <45%, congestion, or both, were randomized to empagliflozin 10 mg or placebo. The primary endpoint was time to first HF hospitalization or all-cause death. Rates of endpoints with and without T2DM and the efficacy and safety of empagliflozin according to T2DM status were assessed. Overall, 32% had T2DM; 14% had pre-diabetes; 16% were normoglycaemic; 38% had unknown glycaemic status. Patients with T2DM, compared to those without T2DM, were at higher risk of time to first HF hospitalization or all-cause death (hazard ratio [HR] 1.44; 95% confidence interval [CI] 1.06-1.95) and all-cause death (HR 1.70; 95% CI 1.13-2.56). T2DM did not confer a higher risk of first HF hospitalization (HR 1.22, 95% CI 0.82-1.83). Empagliflozin reduced first and total HF hospitalizations, but not all-cause mortality, regardless of presence or absence of T2DM. The safety profile of empagliflozin was the same with and without T2DM.

Patients with acute MI, LVEF <45% and/or congestion who had T2DM were at a higher risk of mortality than those without T2DM. Empagliflozin reduced first and total HF hospitalizations regardless of the presence or absence of T2DM.

Since there is no specific recommendation of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in acute myocardial infarction (MI), this systematic review and meta-analysis was performed to address this lack of evidence. Scopus, Embase, PubMed, Web of Sciences, and Cochrane Library were searched from inception until May 30, 2024. We used both random and fixed-effects models for data analyses. Odds ratio (OR) and standard means difference (SMD) were performed for binary and continuous variables, respectively. Nine studies including five randomized clinical trials (RCTs) and four observational studies including 15,595 individuals with acute MI were entered. Overall, SGLT-2 inhibitors are significantly associated with a reduction of hospitalization for heart failure (OR, 0.78; 95% CI, 0.63 to 0.97; P =  .02; I2 = 0%) and all-cause mortality (OR, 0.55; 95% CI, 0.38 to 0.81; P =  .002; I2 = 0%) based on the RCTs and observational studies, respectively. SGLT-2 inhibitors also significantly improved the left ventricular ejection fraction (SMD, 0.36; 95% CI, 0.02 to 0.70; P =  .04; I2 = 62%) among RCTs. Further evaluation of these drugs also revealed an acceptable safety profile without any major adverse events. In conclusion, although SGLT-2 inhibitors may have some clinical benefits among acute MI individuals, further RCTs are still needed to provide robust evidence regarding the use of SGLT-2 inhibitors in this setting.

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

The inclusion of immunomodulatory strategies as supportive therapies in ischemic heart disease (IHD) has garnered significant support over recent years. Several such approaches appear to be unified through their ultimate target, the NLRP3 inflammasome. This review presents a brief update on immunomodulatory strategies in the continuum of conditions constituting ischemic heart disease and emphasising on the seemingly unifying mechanism of NLRP3 activation as well as modulation across these conditions.

The NLRP3 inflammasome is a multiprotein complex assembled upon inflammatory stimulation, causing the release of pro-inflammatory cytokines and initiating pyroptosis. The NLRP3 pathway is relevant in inflammatory signalling of cardiac immune cells as well as non-immune cells in the myocardium, including cardiomyocytes, fibroblasts and endothelial cells. In addition to a focus on clinical outcome and efficacy trials of targeting NLRP3-related pathways, the potential connection between immunomodulation in cardiology and the NLRP3 pathway is currently being explored in preclinical trials. Colchicine, cytokine-based approaches and SGLT2 inhibitors have emerged as promising agents. However, the conditions comprising IHD including atherosclerosis, coronary artery disease (CAD), myocardial infarction (MI) and ischemic cardiomyopathy/heart failure (iCMP/HF) are not equally amenable to immunomodulation with the respective drugs. Atherosclerosis, coronary artery disease and ischemic cardiomyopathy are affected by chronic inflammation, but the immunomodulatory approach to acute inflammation in the post-MI setting remains a pharmacological challenge, as detrimental and regenerative effects of myocardial inflammation are initiated in unison. The NLRP3 inflammasome lies at the center of cell mediated inflammation in IHD. Recent trial evidence has highlighted anti-inflammatory effects of colchicine, interleukin-based therapy as well as SGLT2i in IHD and that the respective drugs modulate the NLRP3 inflammasome.

Sodium‒glucose cotransporter 2 (SGLT2) inhibitors have been included in heart failure (HF) guidelines because of their benefits in reducing mortality and hospitalization rates. However, the timing and benefits of initiating SGLT2 inhibitors in patients after myocardial infarction (MI) remain controversial. Therefore, we aimed to perform a systematic review and meta-analysis comparing SGLT2 inhibitors with placebo in patients with MI.

We performed a systematic review and meta-analysis to determine the impact of SGLT2 inhibitors in patients with recent or previous MI. We systematically searched PubMed, Cochrane, and Embase for RCTs comparing SGLT2 inhibitors versus placebo in patients with MI. The primary outcome was (1) HF hospitalization. In this analysis, we also included the following secondary outcomes: (2) major adverse cardiovascular events (MACE) defined as a composite of cardiovascular (CV) death, MI or stroke; and (3) all-cause mortality. A subgroup analysis was conducted for the primary outcome, comparing patients who had experienced an MI more than 8 weeks prior to study enrolment (previous MI) versus those who had experienced an MI within the preceding 8 weeks (acute MI). Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled with a random effects model.

Our meta-analysis included 10 RCTs comprising 22,266 patients, of whom 11,339 (51.2%) had type 2 diabetes. The mean age was 62 years, and the median follow-up was 21 months. According to the pooled analysis, HF hospitalization rates were lower in patients on SGLT2 inhibitors compared with placebo (RR 0.77; 95% CI 0.69, 0.85; p < 0.001)). Differences in MACE were also observed in favor of SGLT2 inhibitors versus placebo (RR 0.88; 95% CI 0.79, 0.97; p = 0.012). There was no statistically significant difference in all-cause mortality between the groups (RR 0.88; 95% CI 0.78, 1.00; p = 0.058). Benefits of SGLT2 inhibitors for the primary outcome were consistent regardless of the timing of last MI, with no treatment by subgroup interaction (p for interaction = 0.56).

In this meta-analysis of patients who experienced MI, the administration of SGLT2 inhibitors was associated with lower rates of hospitalization for HF. In addition, the treatment effect of SGLT2 inhibitors was consistent regardless of whether they were started in the recent versus previous MI setting.

In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article.

Unexpected cardiovascular events are likely to occur within a short period following an acute myocardial infarction (AMI). The sodium-glucose co-transporter 2 inhibitor (SGLT2-I) is a recently recommended drug for the treatment of AMI. However, its role in the risk of the outcomes following an AMI, including all-cause death and heart failure readmission, remains controversial. Therefore, in this study, we explored the effect of SGLT2-Is on cardiovascular outcomes after an AMI.

PubMed, Web of Science, and Embase were searched without language restrictions to retrieve case-control studies published before April 2024. Citations were independently screened by two authors, and the studies meeting the predefined inclusion criteria were retained. Data on author names, year of publication, location of the study group, gender and age of participants, outcome assessment, adjusted odds ratios (ORs) and 95% confidence intervals (CIs), and the follow-up period were extracted.

Eight studies were eligible for inclusion, and these studies showed that the use of SGLT2-Is after an AMI was significantly associated with a lower risk of hospitalization for heart failure (OR: 0.66, 95% CI 0.57-0.76, p < 0.01) and a lower incidence of major cardiovascular adverse events (OR: 0.79, 95% CI 0.70-0.89, p < 0.01), but was unrelated to a lower incidence of all-cause mortality (OR: 0.84, 95% CI 0.69-1.02, p = 0.07).

Compared with placebo, SGLT2-I therapy following an AMI can reduce the risk of heart failure hospitalization and the incidence of major cardiovascular adverse events, but has no effect on all-cause mortality.

CRD42024542335, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024542335.

Type 2 diabetes mellitus (T2DM) represents a major healthcare condition of the 21st century. It is characterised by persistently elevated blood glucose occurring as a result of peripheral insulin resistance and reduced insulin production which may lead to multiple long-term health conditions such as retinopathy, neuropathy, and nephropathy. The estimated number of individuals suffering from diabetes mellitus (DM) is expected to rise to 591 million by the year 2035 with 4.4 million in the United Kingdom (UK) alone, 90% of which is attributed to T2DM. Moreover, a significant proportion of individuals may have undetected diabetes mellitus, especially among those presenting with symptoms of ischaemic heart disease (IHD). This is particularly important in those individuals presenting with acute coronary syndromes (ACS) who are at the highest risk of complications and sudden cardiac death. Identifying abnormal levels of common biochemical markers of diabetes, such as capillary blood glucose or glycated haemoglobin (HbA1c) in these patients is important for early diagnosis, which will then allow for timely intervention to improve outcomes. However, a significant proportion of individuals who meet the criteria for the diagnosis of diabetes remain undiagnosed, representing missed opportunities for early intervention. This may result in a prolonged period of untreated hyperglycaemia, which can result resulting in significant further microvascular and macrovascular complications. There is an increased risk of IHD, heart failure, cerebrovascular accidents (CVA), and peripheral artery disease (PVD). These account accounting for 50% of deaths in patients with T2DM. Cardiovascular diseases in the context of diabetes particular represent a significant cause of morbidity and mortality with a two to three times higher risk of cardiovascular disease in individuals with T2DM than in those without the condition normo-glycaemia. In the United Kingdom UK alone, around 120 amputations, 770 CVA, 590 heart attacks, and more than 2300 presentations with heart failure per week are attributed to diabetes DM. with One 1 in six 6 hospital beds and around 10% of the healthcare budget may be being spent on managing diabetes DM or its complications. Therefore, it represents a significant burden on our healthcare system.

The impact of sodium-glucose cotransporter-2 (SGLT2) inhibitors on mortality following myocardial infarction (MI) remains uncertain. Additionally, the role of type 2 diabetes mellitus (T2DM) and heart failure (HF) in modulating the effectiveness of these drugs post-MI are not fully understood. This meta-analysis aimed to assess the association of SGLT2 inhibitors with all-cause mortality in post-MI patients and to explore key moderators influencing this benefit.

PubMed, Embase, and Scopus were searched for randomized controlled trials (RTCs) and propensity score-matched (PSM) observational studies assessing SGLT2 inhibitors' impact on post-MI mortality. The primary outcome was all-cause mortality. We pooled hazard ratios (HRs) to estimate the intervention's effect on the overall population and stratified studies into early (SGLT2 inhibitors administered within eight weeks post-MI) and delayed treatment trials. Meta-regression assessed the moderating effects of T2DM and HF.

 A total of five RCTs and four PSM observational studies involving 26,753 patients (mean [SD] age, 62.9 [10.5] years; 6,406 female [24.0%]; 16,369 T2DM [61.2%]; 13,933 HF [52.1%]) were included. Early and delayed treatment trials comprised 16,165 (60.4%) and 10,588 (39.6%) patients, respectively. SGLT2 inhibitors reduced all-cause mortality following MI (HR 0.79, 95% CI [0.68, 0.91]; p = 0.001; I2 = 59%). Stratified analysis demonstrated consistent effects in both early (HR 0.76, 95% CI [0.59, 0.98]; p = 0.03; I2 = 65%) and delayed (HR 0.81, 95% CI [0.67, 0.98]; p = 0.03; I2 = 60%) treatment. Meta-regression identified T2DM as a significant moderator of the mortality benefit (β = - 0.0049; p = 0.0006).

In this meta-analysis, early and delayed treatment with SGLT2 inhibitors following MI was associated with a significant reduction in all-cause mortality. Furthermore, the presence of T2DM was associated with a greater mortality reduction, while HF was not significantly associated with the outcome.

Data on the early use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in patients with acute heart failure (HF) are conflicting, and mostly evaluating soft endpoints (i.e., indices of congestion, renal function, ejection fraction, and diuresis). The aim was to perform a meta-analysis of randomized controlled trials (RCTs) to assess their impact after an HF decompensation event.

Two electronic databases were screened for eligible studies. Efficacy endpoints were all-cause death, cardiovascular death, HF hospitalization, length of hospital stay, and N-terminal pro-B-type natriuretic peptide (nt-proBNP). Safety endpoints included acute kidney injury (AKI), volume depletion, ketoacidosis, hypotension, hypoglycemia, non-cardiovascular death, urinary tract infection, genital infections, serious adverse events (AE), and AE leading to treatment discontinuation. Two pre-specified subgroup analyses were planned according to the specific SGLT2i and clinical setting [i.e., acute myocardial infarction (MI) versus non-acute MI]. 16 RCTs enrolling 15,073 patients were considered. Early initiation of SGLT2i significantly reduced the risk of HF hospitalizations [Risk ratio (RR) 0.79, 95 % Confidence interval (CI) 0.72-0.87], AKI (RR 0.76, 95 % CI 0.59-0.99), and nt-proBNP levels (MD -354 pg/mL). No significant difference was detected for any of the other endpoints. In the pre-specified subgroup analysis, a significant interaction was found between the SGLT2i type and the risk of AKI, in favor of empagliflozin.

In patients recently hospitalized for acute HF, early administration of SGLT2i was associated with fewer readmissions for HF and AKI, as well as decongestant effects, without raising any safety concern.

Randomized controlled trials (RCTs) are the cornerstone of modern evidence-based medicine. They are considered essential to establish definitive evidence of efficacy and safety for new drugs, and whenever possible they should also be the preferred method for investigating new high-risk medical devices. Well-designed studies robustly inform clinical practice guidelines and decision-making, but administrative obstacles have made it increasingly difficult to conduct informative RCTs. The obstacles are compounded for RCTs of high-risk medical devices by extra costs related to the interventional procedure that is needed to implant the device, challenges with willingness to randomize patients throughout a trial, and difficulties in ensuring proper blinding even with sham procedures. One strategy that may help is to promote the wider use of simpler and more streamlined RCTs using data that are collected routinely during healthcare delivery. Recent large simple RCTs have successfully compared the performance of drugs and of high-risk medical devices, against alternative treatments; they enrolled many patients in a short time, limited costs, and improved efficiency, while also achieving major impact. From a task conducted within the CORE-MD project, we report from our combined experience of designing and conducting large pharmaceutical trials during the COVID-19 pandemic, and of planning and coordinating large registry-based RCTs of cardiovascular devices. We summarize the essential principles and utility of large simple RCTs, likely applicable to all interventions but especially in order to promote their wider adoption to evaluate new medical devices.

Cardiovascular disease is on the rise globally, with ischemic heart disease being the leading cause of mortality and morbidity. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve cardiovascular outcomes in patients with heart failure, evidence is limited in guiding initiation in post-acute myocardial infarction (post-AMI) patients. Hence, this study aimed to appraise the current literature on the effect of SGLT2i on the clinical outcomes of post-AMI patients.

A comprehensive search of PubMed, EMBASE, SCOPUS, and ClinicalTrials.gov was conducted up to 1 May 2024. Only randomized controlled trials studying the use of SGLT2i in post-AMI patients were included. We included adult patients aged 18 years old and older diagnosed with AMI and initiated on SGLT2i in the acute post-AMI setting. SGLT2i studies solely in heart failure settings were excluded.

Eight clinical trials were included in the systematic review, comprising 11,436 patients. Compared with placebo, SGLT2i initiation in post-AMI patients significantly reduced total number of heart failure hospitalizations (risk ratio [RR] 0.74, 95% confidence interval [CI] 0.62-0.90) and was associated with a lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (- 26.67 pg/ml, 95% CI - 41.74 to - 11.59). There was no difference in all-cause mortality (RR 1.02, 95% CI 0.81-1.28), cardiovascular mortality (RR 1.03, 95% CI 0.83-1.28), change in left ventricular ejection fraction, and glycated hemoglobin (HbA1c), as compared with placebo.

SGLT2i use in patients with AMI was associated with a reduction in heart failure hospitalizations and a decrease in NT-proBNP. There were no significant differences in mortality outcomes.

PROSPERO identifier number CRD42024540843.

We aimed to assess the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus placebo, initiated within the hospitalization period, in addition to habitual treatment, for treating adult patients with confirmed acute myocardial infarction (AMI). We also conducted subgroup analysis by diabetes mellitus (DM) status and type of AMI. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcome was hospitalization for heart failure (HF). The secondary outcomes were all-cause death, cardiovascular death, and serious adverse events (AEs). We pooled risk ratios (RR) with a 95% confidence interval (CI) for binary outcomes. The between-study variance was assessed using tau2 statistics. We included five RCTs, encompassing 11,211 patients. SGLT2i significantly reduced the risk of hospitalization for HF compared to placebo (RR 0.73; 95% CI [0.61, 0.88]). However, the risk of all-cause death (RR 1.05; 95% CI [0.78, 1.41]) and cardiovascular death (RR 1.04; 95% CI [0.84, 1.29]) was similar between the groups, as well as the risk of serious AEs (RR 1.01; 95% CI [0.90, 1.14]). In the subgroup analysis by DM status and type of AMI, there were no significant subgroup differences for the outcomes of hospitalization for HF and all-cause death. In patients with AMI, treatment with SGLT2i is safe and significantly reduces the risk of hospitalization for HF, but it has no impact on all-cause death and cardiovascular death compared to placebo.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors provide cardiovascular and kidney benefits to patients with heart failure (HF) and/or chronic kidney disease (CKD), regardless of diabetes status and left ventricular ejection fraction (LVEF). Despite robust data demonstrating the efficacy of SGLT-2 inhibitors in both ambulatory and hospital settings, real-world evidence suggests slow and varied adoption of SGLT2 inhibitors among patients hospitalized for HF. Barriers to implementation of SGLT2i may include clinicians' concerns regarding potential adverse events such as diabetic ketoacidosis (DKA), volume depletion, and symptomatic hypoglycemia; or concerns regarding physiologically expected reductions in eGFR. Guidelines lack specific, practical safety data and definitive recommendations regarding in-hospital initiation and continuation of SGLT2i in patients hospitalized with HF. In this review, we discuss the safety of in-hospital SGLT2 inhibitor initiation based on recent trials and highlight the clinical implications of their early use in patients hospitalized for HF.

Empagliflozin treatment before acute myocardial infarction mainly targets the endothelial cell transcriptome. Empagliflozin treatment before and after myocardial infarction decreased no reflow and microvascular injury, leading to reduced infiltration of inflammatory cells, reduced infarct size, and improved cardiac function in mice. In diabetic patients receiving empagliflozin after myocardial infarction, perfused boundary region, flow-mediated dilation, and global longitudinal strain were improved.