Cardiovascular outcomes with sodium-glucose cotransporter-2 inhibitors vs other glucose-lowering drugs in 13 countries across three continents : analysis of CVD-REAL data

Background Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. Methods De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects. Results Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58-0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45-0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53-0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78-0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72-0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region. Conclusions This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614Peer reviewe

Report from the CVOT Summit 2020:new cardiovascular and renal outcomes

The 6th Cardiovascular Outcome Trial (CVOT) Summit "Cardiovascular and Renal Outcomes 2020" was the first to be held virtually on October 29-30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA- CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed. The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18-19, 2021 (http://www.cvot.org)

Temporal trends in the management of severe hyperglycemia among patients hospitalized with acute myocardial infarction [abstract]

Poster sesssionBackground: Elevated blood glucose (BG) is associated with an adverse prognosis in acute myocardial infarction (AMI) patients. While guidelines recommend insulin therapy to lower markedly elevated BG in AMI patients, it is unknown whether these recommendations have impacted BG management over time. Methods: We studied 39,775 AMI patients hospitalized from 2000 to 2008 in 55 US medical centers contributing to Health Facts, a national database with extensive data on in-hospital BG and insulin use. Using all available BG measures during the hospital stay, we restricted our analysis to patients with a mean BG ≥200mg/dl and examined temporal trends in insulin use with hierarchical logistic regression models. Results: Overall, 4330 patients (11% of the entire cohort) had mean hospitalization BG ≥ 200 mg/dL and this proportion decreased from 2000 to 2008 (12% to 8%, p for trend<0.001); 75% of these patients had diabetes. In total, 61% of AMI patients with mean BG ≥ 200 received any insulin and only 16% received intravenous (IV) insulin during hospitalization. Hierarchical multivariable models showed an increased likelihood of insulin use over time (Figure). However, about one in three patients continued to receive no treatment for markedly elevated BG. Conclusions: Despite some improvement over time, insulin treatment rates among hospitalized AMI patients with severe, sustained hyperglycemia remain low. These findings likely reflect continuing uncertainty regarding optimal BG management during AMI

Trends in the Prevalence of Acute Kidney Injury in Patients with Acute Myocardial Infarction

Comparative Medicine - OneHealth and Comparative Medicine Poster SessionIntroduction: Acute kidney injury (AKI) is common in patients (pts) with acute myocardial infarction (AMI), and associated with permanent renal impairment and death. While guidelines increasingly emphasize the importance of AKI prevention, whether the rates of AKI changed over time is unknown. Methods: We studied 35,425 pts hospitalized with AMI in 66 U.S. centers from 2000-08 using Health Facts, a national database with detailed information on in-hospital renal function. AKI was defined as absolute creatinine increase of ≥ 0.3 mg/dL or relative increase of ≥50%. Temporal trends in AKI during the 9-year study period were evaluated using hierarchical logistic regression, adjusting for secular changes in baseline creatinine and other known AKI predictors. Results: From 2000-08, mean age increased (66.9 vs 68.8 yrs), as did baseline creatinine (1.4 vs 1.5 mg/dL), rate of cardiogenic shock (5.1 vs 6.3%), diabetes (30.4 vs 35.8%), coronary angiography (57 vs 68%), and PCI (30.2 vs 45.2%, P<0.001 for all comparisons). Despite increase in AKI risk factors, the rates of AKI declined steadily (Figure). The trend of decreasing AKI rates persisted after multivariable adjustment (P=0.01). Conclusions: While AKI still affects nearly 1 in 4 AMI pts, the rates of AKI declined significantly from 2000-08, despite the aging population and rising prevalence of AKI risk factors. These findings may reflect the impact of increased clinician awareness, better risk stratification, and AKI prevention efforts during this time period

Renal outcomes and all-cause death associated with sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL 3 Korea)

Aims To investigate the effectiveness of sodium-glucose co-transporter-2 (SGLT2) inhibitors on the risk of progression to end-stage renal disease (ESRD) and all-cause mortality in a broad range of patients with type 2 diabetes (T2D) using a Korean nationwide cohort. Materials and Methods Using data from the Korean National Health Insurance Service database from January 2014 to December 2017, a total of 701 674 patients were identified with T2D. We divided these patients into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs (oGLDs). Using propensity scores, patients in the two groups were matched 1:1. We assessed the risk of ESRD and all-cause death. Results There were 45 016 patients in each group, and baseline characteristics were well balanced between the groups. The patients' mean age was 58.1 +/- 10.6 years and mean estimated glomerular filtration rate (eGFR) was 89.2 +/- 27.4 mL/min/1.73m(2), and 8% of patients had proteinuria. We identified 167 incident ESRD cases and 1070 all-cause deaths during follow-up. Use of SGLT2 inhibitors versus oGLDs was associated with a lower risk of ESRD (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.34 to 0.65) and all-cause death (HR 0.82, 95% CI 0.73 to 0.93). In a subgroup analysis by eGFR, initiation of SGLT2 inhibitor treatment, compared with oGLD treatment, was associated with lower risk of progression to ESRD among patients with eGFR 60 to 90 mL/min/1.73m(2) and those with eGFR = 90 and 60 to 90 mL/min/1.73m(2). Conclusion In this large nationwide study of Korean patients with T2D, initiation of SGLT2 inhibitors versus oGLDs was associated with lower risk of ESRD and all-cause death

Study design of real world evidence for treatment of hyperkalemia in the emergency department (REVEAL-ED): A multicenter, prospective, observational study

OBJECTIVE: Hyperkalemia affects up to 10% of hospitalized patients and, if left untreated, can lead to serious cardiac arrhythmias or death. Although hyperkalemia is frequently encountered in the emergency department (ED), and is potentially life-threatening, standard of care for the treatment is poorly defined, with little supporting evidence. The main objectives of this observational study are to define the overall burden of hyperkalemia in the ED setting, describe its causes, the variability in treatment patterns and characterize the effectiveness and safety of ED standard of care therapies used in the United States. METHODS: This is an observational study evaluating the management of hyperkalemia in the ED. Two hundred and three patients who presented to the ED with a potassium value ≥5.5 mmol/L were enrolled in the study at 14 sites across the United States. Patients were treated per standard of care practices at the discretion of the patient\u27s physician. In patients who received a treatment for hyperkalemia, blood samples were drawn at pre-specified time points and serum potassium values were recorded. The change in potassium over 4 hours and the adverse events after standard of care treatment were analyzed. RESULTS AND CONCLUSION: This article describes the background, rationale, study design, and methodology of the REVEAL-ED (Real World Evidence for Treatment of Hyperkalemia in the Emergency Department) trial, a multicenter, prospective, observational study evaluating contemporary management of patients admitted to the ED with hyperkalemia

Cardiovascular and mortality benefits of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus : CVD-Real Catalonia

Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain. CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke). After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47-0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31-0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47-0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52-0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54-0.80; p < 0.001). In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD. The online version contains supplementary material available at 10.1186/s12933-021-01323-5

Novel Trial Design: CHIEF-HF

BACKGROUND: The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms. METHODS: One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (\u3e40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire. RESULTS: The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial

The Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial: baseline characteristics

The aims of this study were to: (i) report the baseline characteristics of patients enrolled in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial, (ii) compare DAPA-HF patients to participants in contemporary heart failure (HF) registries and in other recent HF trials, and (iii) compare individuals with diabetes, pre-diabetes and a normal glycated haemoglobin (HbA1c) in DAPA-HF. Adults with HF in New York Heart Association functional class ≥ II, a left ventricular ejection fraction ≤ 40%, an elevated N-terminal pro-B-type natriuretic peptide concentration and receiving standard treatment were eligible for DAPA-HF, which is comparing dapagliflozin 10 mg once daily to matching placebo. In patients without a history of diabetes, previously undiagnosed diabetes was defined as a confirmed HbA1c ≥ 6.5%. Among patients without known or undiagnosed diabetes, pre-diabetes was defined as a HbA1c ≥ 5.7% The remainder of patients, with a HbA1c &lt; 5.7%, were defined as normoglycaemic. Of the 4774 patients (mean age 66 years; 23% women) randomized, 42% had known diabetes and 3% undiagnosed diabetes. Of the remainder, 67% had pre-diabetes and 33% normal HbA1c. Overall, DAPA-HF patients were generally similar to those in recent registries and in relevant trials and had high levels of background therapy: 94% angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, 96% beta-blocker, and 71% mineralocorticoid receptor antagonist; 26% had a defibrillator. Patients with diabetes had worse HF status, more co-morbidity, and greater renal impairment but received similar HF therapy. Patients with diabetes received non-insulin hypoglycaemic therapy alone in 49%, insulin alone in 11%, both in 14%, and none in 26%. Patients randomized in DAPA-HF were similar to those in other contemporary HF with reduced ejection fraction (HFrEF) registries and trials. These patients were receiving recommended HFrEF therapy and those with diabetes were also treated with conventional glucose-lowering therapy. Consequently, DAPA-HF will test the incremental efficacy and safety of dapagliflozin in HFrEF patients with and without diabetes