Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction
Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction.
Summary
Insights From the EMPACT-MI Trial
[Posted 21/May/2024]
AUDIENCE: Cardiology, Emergency Medicine
KEY FINDINGS: Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction.
BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown.
DETAILS: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of 45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes. Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P=0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P=0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P<0.05).
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Source: Hernandez, A. F., Udell, J. A., Jones, W. S., et al. (2024). Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial. XXXXX. 2024; 149: 1627-1638. Published: May, 2024. DOI: 10.1161/CIRCULATIONAHA.124.069217.
A Simple Blood Test Warns of Possible Cardiometabolic Complications for Children With Obesity
Scientists from the University of Copenhagen have detected lipid biomarkers in children and teenagers with obesity that indicate an increased risk of developing type 2 diabetes, liver and heart disease as adults. A one-year lifestyle intervention lowered the levels of these lipid biomarkers, which demonstrates the importance of early intervention for children with obesity.
KEY FINDINGS: Scientists from the University of Copenhagen have detected lipid biomarkers in children and teenagers with obesity that indicate an increased risk of developing type 2 diabetes, liver and heart disease as adults. A one-year lifestyle intervention lowered the levels of these lipid biomarkers, which demonstrates the importance of early intervention for children with obesity.
BACKGROUND: The number of children and teens with obesity is increasing worldwide, with over 250 million expected to be affected by 2030. It is a major public health crisis, as children with obesity risk developing insulin resistance, fatty liver, and high blood pressure, which may lead to diseases such as cardiovascular disease, type 2 diabetes and liver disease, later in life.
DETAILS: Scientists think these diseases can be triggered by changes in the body's lipids -- a wide range of fats and oils in the body including triglycerides and cholesterol that serve many purposes including energy storage and cellular signalling. But it is still not well understood how lipid species change in children with obesity, and how they are linked to early cardiometabolic complications.
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Now, scientists at the University of Copenhagen have discovered that lipid species linked to cardiometabolic disease in adults are strongly associated with cardiometabolic risk factors in children and teenagers with obesity. The findings could pave the way for tests that serve as an early warning system for cardiometabolic disease.
"Our study shows that the impact of cardiometabolic associated lipid species emerges early in life in children with obesity, particularly affecting liver function and glucose metabolism. These risk lipid species could potentially be explored further as biomarkers for diagnosing or predicting cardiometabolic risk in children at high risk, offering new insights for early detection and intervention," says Postdoc Yun Huang from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, and co-first author of the study in Nature Medicine.
Early intervention reverses cardiometabolic disease risk
The scientists made their discoveries by drawing on the HOLBAEK Study biobank of more than 4,000 children with and without obesity. at the Children's Obesity Clinic at Holbaek Hospital. Together with scientists at Steno Diabetes Center Copenhagen, they harnessed powerful mass spectrometry technology to map hundreds of individual lipid species, each with distinct structures and functions, providing a detailed picture of lipid metabolism. By analyzing the differences in the lipid profiles of 958 children with overweight or obesity and 373 who had normal weight, they gained deep insight into obesity altered lipid profiles and their link to cardiometabolic risk, and the ability to detect excessive fat in the liver.
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Source: University of Copenhagen - The Faculty of Health and Medical Sciences (2024). A Simple Blood Test Warns of Possible Cardiometabolic Complications for Children With Obesity. ScienceDaily. 2024; Published: September 20, 2024. DOI: 10.1038/s41591-024-03279-x.
Utilization and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Hypertrophic Cardiomyopathy
Despite a stable prevalence of SCD risk factors, ICD utilization for prevention of SCD among patients with HCM has increased over time, including among older patients with HCM in whom ICD use is generally considered controversial. Among older patients with HCM who received a primary prevention ICD, NSVT was the most common risk factor for SCD and, along with NYHA class, was strongly associated with future admission for ventricular arrhythmia or cardiac arrest.
KEY FINDINGS: Primary prevention ICD utilization in patients with hypertrophic cardiomyopathy increased over time, including among those >=65 years old. Among older patients, the strongest risk factors for hospitalization for ventricular arrhythmia/cardiac arrest following ICD implantation were history of nonsustained ventricular tachycardia and New York Heart Association class.
BACKGROUND: There is uncertainty about the appropriate use of primary prevention implantable cardioverter-defibrillators (ICDs) among older patients with hypertrophic cardiomyopathy.
DETAILS: Patients with hypertrophic cardiomyopathy who received a primary prevention ICD between 2010 and 2016 were identified using the National Cardiovascular Data Registry ICD Registry. Trends in ICD utilization and patient characteristics were assessed over time. Using linked Centers for Medicare and Medicaid Service claims data, Cox proportional hazard models assessed factors associated with mortality and postdischarge hospitalization for cardiac arrest/ventricular arrhythmia. Of 5571 patients with hypertrophic cardiomyopathy, 1511 (27.1%) were >=65 years old. ICD utilization increased over time in all age groups. There were no changes in the prevalence of risk factors for sudden cardiac death over time. The variables most strongly associated with postdischarge mortality were older age (adjusted hazard ratio (aHR) 1.80 [95% CI, 1.47-2.21]), New York Heart Association class (III/IV versus I/II aHR 2.17 [95% CI, 1.57-2.98]), and left ventricular ejection fraction (left ventricular ejection fraction <=35% versus >50% aHR 2.34 [95% CI, 1.58-3.48]; left ventricular ejection fraction 36%-50% versus >50% aHR 2.98 [95% CI, 2.02-4.40]), while history of nonsustained ventricular tachycardia (aHR 2.38 [95% CI, 1.62-3.51]) and New York Heart Association class (III/IV versus I/II aHR 1.84 [95% CI, 1.22-2.78]) were strongly associated with hospitalization for ventricular arrhythmia/cardiac arrest.
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Source: Goldstein, S. A., Kennedy, K. F., Friedman, D. J., et al. (2024). Utilization and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Hypertrophic Cardiomyopathy. J Am Heart Ass. 2024; 12(16): e029293. Published: August 15, 2024. DOI: 10.1161/JAHA.122.02929.
Effect of SGLT2 Inhibitors on Heart Failure Outcomes and Cardiovascular Death Across the Cardiometabolic Disease Spectrum
SGLT2 inhibitors reduced heart failure events and cardiovascular death in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease. These effects were consistent across a wide range of subgroups within these populations. This supports the eligibility of a large population with cardiorenal-metabolic diseases for treatment with SGLT2 inhibitors.
Summary
A Systematic Review and Meta-Analysis
[Posted 14/Jul/2024]
AUDIENCE: Endocrinology, Cardiology
KEY FINDINGS: SGLT2 inhibitors reduced heart failure events and cardiovascular death in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease. These effects were consistent across a wide range of subgroups within these populations. This supports the eligibility of a large population with cardiorenal-metabolic diseases for treatment with SGLT2 inhibitors.
BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been studied in patients with heart failure, type 2 diabetes, chronic kidney disease, atherosclerotic cardiovascular disease, and acute myocardial infarction. Individual trials were powered to study composite outcomes in one disease state. We aimed to evaluate the treatment effect of SGLT2 inhibitors on specific clinical endpoints across multiple demographic and disease subgroups.
DETAILS: In this systematic review and meta-analysis, authors queried online databases (PubMed, Cochrane CENTRAL, and SCOPUS) up to Feb 10, 2024, for primary and secondary analyses of large trials (n>1000) of SGLT2 inhibitors in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease (including acute myocardial infarction). Outcomes studied included composite of first hospitalisation for heart failure or cardiovascular death, first hospitalisation for heart failure, cardiovascular death, total (first and recurrent) hospitalisation for heart failure, and all-cause mortality. Effect sizes were pooled using random-effects models. Authors included 15 trials (N=100,952). Compared with placebo, SGLT2 inhibitors reduced the risk of first hospitalisation for heart failure by 29% in patients with heart failure (hazard ratio [HR] 0.71 [95% CI 0.67-0.77]), 28% in patients with type 2 diabetes (0.72 [0.67-0.77]), 32% in patients with chronic kidney disease (0.68 [0.61-0.77]), and 28% in patients with atherosclerotic cardiovascular disease (0.72 [0.66-0.79]). SGLT2 inhibitors reduced cardiovascular death by 14% in patients with heart failure (HR 0.86 [95% CI 0.79-0.93]), 15% in patients with type 2 diabetes (0.85 [0.79-0.91]), 11% in patients with chronic kidney disease (0.89 [0.82-0.96]), and 13% in patients with atherosclerotic cardiovascular disease (0.87 [0.78-0.97]). The benefit of SGLT2 inhibitors on both first hospitalisation for heart failure and cardiovascular death was consistent across the majority of the 51 subgroups studied. Notable exceptions included acute myocardial infarction (22% reduction in first hospitalisation for heart failure; no effect on cardiovascular death) and heart failure with preserved ejection fraction (26% reduction in first hospitalisation for heart failure; no effect on cardiovascular death).
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Source: Usman, M. S., Bhatt, D. L., Hameed, I., et al. (2024). Effect of SGLT2 Inhibitors on Heart Failure Outcomes and Cardiovascular Death Across the Cardiometabolic Disease Spectrum: A Systematic Review and Meta-Analysis. The Lancet. 2024; Published: July, 2024. DOI: 10.1016/S2213-8587(24)00102-5.
MASLD and MASH At the Crossroads of Hepatology Trials and Cardiorenal Metabolic Trials
The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.
KEY FINDINGS: The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.
BACKGROUND: Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease.
DETAILS: Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies.
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Copyright © John Wiley & Sons, Inc. All rights reserved
Source: Zannad, F., Sanyal, A. J., Butler, J., et al. (2024). MASLD and MASH At the Crossroads of Hepatology Trials and Cardiorenal Metabolic Trials. Journal of Internal Medicine. 2024; 296(1): 24-38. Published: July, 2024. DOI: 10.1111/joim.13793.
Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium More Than 1,000
Among asymptomatic patients with a CAC of more than 1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering.
KEY FINDINGS: Among asymptomatic patients with a CAC of >=1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering.
BACKGROUND: Although a coronary artery calcium (CAC) of >=1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high atherosclerotic cardiovascular disease (ASCVD) risk in this patient population is not well-defined. Among persons with a CAC of >=1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates.
DETAILS: The authors studied 2,246 asymptomatic patients with a CAC of >=1,000 from the CAC Consortium without a prior ASCVD event. Cox proportional hazards regression modelling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by >=2 major ASCVD events or 1 major event and >=2 high-risk conditions (1.4 per 100 person-years). The mean age was 66.6 years, 14% were female, and 10% were non-White. The median CAC score was 1,592 and 6% had severe left main (LM) CAC (vessel-specific CAC >=300). Diabetes (HR: 2.04 [95% CI: 1.47-2.83]) and severe LM CAC (HR: 2.32 [95% CI: 1.51-3.55]) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), although higher rates were observed for diabetes (1.4 [95% CI: 0.8-1.9]), severe LM CAC (1.3 [95% CI: 0.6-2.0]), and both diabetes and severe LM CAC (7.1 [95% CI: 3.4-10.8]).
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Copyright © American College of Cardiology Foundation. All rights reserved.
Source: Razavi, A. C., Shaw, L. J., Berman, D. S., et al. (2024). Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium > 1,000. JACC: Cardiovascular Imaging. 2024; 17(7): 766-776. Published: July 1, 2024. DOI: 10.1016/j.jcmg.2023.12.006.
Specialty: