Prevention of heart failure events with sodium-glucose co-transporter 2 inhibitors across a spectrum of cardio-renal-metabolic risk

Aims Trials have tested the safety and efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT2i) across various disease states. We performed a meta-analysis of randomized controlled trials (RCTs) to estimate the relative and absolute effects of SGLT2i in the prevention of heart failure (HF) events across different risk groups. Methods and results We conducted a systematic review and meta-analysis of large, placebo-controlled RCTs with >1000 participants evaluating HF hospitalization and the composite of cardiovascular (CV) death or HF hospitalization. Due to varying durations of therapeutic exposure and follow-up, absolute risk reductions and number needed to treat were calculated based on incidence rates (per 100 patient-years). Across 71 553 patients enrolled in 10 late-phase RCTs, SGLT2i reduced the risk of HF hospitalization by 31% [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.64-0.74; I-2 = 0%] and the composite outcome of CV death or HF hospitalization by 24% (HR 0.76, 95% CI 0.72-0.80; I-2 = 1.4%) compared with placebo. The number of patient-years of treatment exposure needed to prevent one CV death or HF hospitalization ranged from 19-26 (established HF) to 72-125 (chronic kidney disease) to 96-400 (high-risk type 2 diabetes). In mixed-effects meta-regression analyses, the benefits of SGLT2i on HF hospitalizations or the composite outcome (CV death or HF hospitalization) were not influenced by age, sex, or change in intermediate markers (glycated haemoglobin, systolic blood pressure, and body weight) (all P >= 0.10). Conclusion Despite wide variation in baseline risks and disease states evaluated, SGLT2i demonstrated comparable relative risk reductions in preventing HF events. Patients at highest baseline risk derived the greatest absolute benefits in preventing HF events. These composite estimates may help guide targeted implementation of SGLT2i for the prevention of HF events in type 2 diabetes and chronic kidney disease and in the treatment of HF

Trends in Veno-Arterial Extracorporeal Life Support With and Without an Impella or Intra-Aortic Balloon Pump for Cardiogenic Shock

Background: Mechanical circulatory support devices, such as the intra-aortic balloon pump (IABP) and Impella, are often used in patients on veno-arterial extracorporeal life support (VA-ECLS) with cardiogenic shock despite limited supporting clinical trial data. Methods and Results: Hospitalizations for cardiogenic shock from 2016 to 2018 were identified from the National Inpatient Sample. Trends in the use of VA-ECLS with and without an IABP or Impella were assessed semiannually. Multivariable logistic regression and general linear regression evaluated the association of Impella and IABP use with in-hospital outcomes. Overall, 12 035 hospitalizations with cardiogenic shock and VA-ECLS were identified, of which 3115 (26%) also received an IABP and 1880 (16%) an Impella. Use of an Impella with VA-ECLS substantially increased from 10% to 18% over this period (P\u3c0.001), whereas an IABP modestly increased from 25% to 26% (P\u3c0.001). In-hospital mortality decreased 54% to 48% for VA-ECLS only, 61% to 58% for VA-ECLS with an Impella, and 54% to 49% for VA-ECLS with an IABP (P\u3c0.001 each). Most (57%) IABPs or Impellas were placed on the same day as VA-ECLS. After adjustment, there were no differences in in-hospital mortality or length of stay with the addition of an IABP or Impella compared with VA-ECLS alone. Conclusions: From 2016 to 2018 in the United States, use of an Impella and IABP with VA-ECLS significantly increased. More than half of Impellas and IABPs were placed on the same day as VA-ECLS, and the use of a second mechanical circulatory support device did not impact in-hospital mortality. Further studies are needed to decipher the optimal timing and patient selection for this growing practice

Impact of Type 2 Myocardial Infarction (MI) on Hospital‐Level MI Outcomes: Implications for Quality and Public Reporting

Background: The International Classification of Diseases (ICD) coding system does not recognize type 2 myocardial infarction (MI) as a separate entity; therefore, patients with type 2 MI continue to be categorized under the general umbrella of non–ST‐segment–elevation myocardial infarction (NSTEMI). We aim to evaluate the impact of type 2 MI on hospital‐level NSTEMI metrics and discuss the implications for quality and public reporting. Methods and Results: We conducted a single‐center retrospective analysis of 1318 patients discharged with a diagnosis of NSTEMI between July 2013 and October 2014. The Third Universal Definition was used to define type 1 and type 2 MI. Weighted Kaplan–Meier curves were used to analyze risk of mortality and readmission. Overall, 1039 patients met NSTEMI criteria per the Third Universal Definition; of those, 264 (25.4%) had type 2 MI. Patients with type 2 MI were older, were more likely to have chronic kidney disease, and had lower peak troponin levels. Compared with type 1 MI patients, those with type 2 MI had higher inpatient mortality (17.4% versus 4.7%, P<0.0001) and were more likely to die from noncardiovascular causes (71.7% versus 25.0%, P<0.0001). Despite weighting for patient characteristics and discharge medications, patients with type 2 MI had higher mortality at both 30 days (risk ratio: 3.63; 95% confidence interval, 1.67–7.88) and 1 year (risk ratio: 1.98; 95% confidence interval, 1.44–2.73) after discharge. Type 2 MI was also associated with a lower 30‐day cardiovascular‐related readmission (risk ratio: 0.49; 95% confidence interval, 0.12–2.06). Conclusions: NSTEMI metrics are significantly affected by type 2 MI patients. Type 2 MI patients have distinct etiologies, are managed differently, and have higher mortality compared with patients with type 1 MI. Moving forward, it may be appropriate to exclude type 2 MI data from NSTEMI quality metrics

Differential association of plasma angiopoietin-like proteins 3 and 4 with lipid and metabolic traits.

OBJECTIVE: Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) are secreted proteins that inhibit lipoprotein lipase in vitro. Genetic variants at the ANGPTL3 and ANGPTL4 gene loci are significantly associated with plasma lipid traits. The aim of this study was to evaluate the association of plasma ANGPTL3 and ANGPTL4 concentrations with lipid and metabolic traits in a large community-based sample. APPROACH AND RESULTS: Plasma ANGPTL3 and ANGPTL4 levels were measured in 1770 subjects using a validated ELISA assay. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, sex, and race were performed. ANGPTL3 levels were significantly positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels (both P CONCLUSIONS: Despite having similar biochemical effects in vitro, plasma ANGPTL3 and ANGPTL4 concentrations have nearly opposite relationships with plasma lipids. ANGPTL4 is strongly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and positively with multiple features of the metabolic syndrome including triglycerides, whereas ANGPTL3 is positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and not with metabolic syndrome traits including triglycerides. Although ANGPTL3 and ANGPTL4 both inhibit lipoprotein lipase in vitro and influence lipoprotein metabolism in vivo, the physiology of these related proteins and their effects on lipoproteins is clearly divergent and complex