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Clinical and Biomarker Predictors of Expanded Heart Failure Outcomes in Patients With Type 2 Diabetes Mellitus After a Recent Acute Coronary Syndrome: Insights From the EXAMINE Trial.

ABSTRACT: Background Improved heart failure (HF) risk stratification after a recent acute coronary syndrome may identify those who can benefit from therapies that reduce HF risk. We aimed to identify clinical and biomarker predictors for expanded HF outcomes in patients with type 2 diabetes mellitus after recent acute coronary syndrome. Methods and Results The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial was a multicenter, non-inferiority, double-masked, placebo-controlled study which randomized 5380 patients with type 2 diabetes mellitus after recent acute coronary syndrome to alogliptin or placebo. Baseline biomarkers were measured in 5154 patients: NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin I, adiponectin, growth-differentiation-factor-15, and galectin-3. Our primary outcome was cardiovascular) death, HF hospitalization, elevated NT-proBNP during follow-up, or loop diuretics initiation. The association between clinical variables, biomarkers, and outcomes were assessed using Cox regression models. In the study population, the median age was 61.0 years, 67.7% were men, and 28.0% had baseline HF (median follow-up was 18 months). In multivariable analyses, NT-proBNP had the strongest association with the primary outcome (per log2, hazard ratio 1.24; Wald ?2 67.4; P<0.0001) followed by a prior HF history (hazard ratio 1.42; Wald ?2 20.8; P<0.0001). A model with clinical variables and biomarkers allowed for risk prediction for expanded HF outcomes (C-statistic=0.72). Discrimination results were similar for cardiovascular death or HF hospitalization. Conclusions Among patients with type 2 diabetes mellitus after recent acute coronary syndrome, the use biomarkers such as N-terminal pro-B-type natriuretic peptide and clinical variables enables risk stratification for expanded HF outcomes. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00968708.

SUBMITTER: Sharma A

PROVIDER: S-EPMC6988143 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Clinical and Biomarker Predictors of Expanded Heart Failure Outcomes in Patients With Type 2 Diabetes Mellitus After a Recent Acute Coronary Syndrome: Insights From the EXAMINE Trial.

Sharma Abhinav A Vaduganathan Muthiah M Ferreira João Pedro JP Liu Yuyin Y Bakris George L GL Cannon Christopher P CP White William B WB Zannad Faiez F

Journal of the American Heart Association 20200104 1

Background Improved heart failure (HF) risk stratification after a recent acute coronary syndrome may identify those who can benefit from therapies that reduce HF risk. We aimed to identify clinical and biomarker predictors for expanded HF outcomes in patients with type 2 diabetes mellitus after recent acute coronary syndrome. Methods and Results The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial was a multicenter, non-inferiority, double-masked, p ...[more]

PMID: 31902327

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Project description:Background:Chronic heart failure (CHF) is a global health burden. Despite advances in treatment, there remain well-recognised morbidity and mortality. Risk stratification requires the identification and validation of biomarkers, old and new. Hyponatremia has re-emerged as a prognostic marker in CHF patients. Methods:This is a retrospective cohort study on 241 CHF patients recruited from King Fahd Hospital of the University, Al-Khobar, Saudi Arabia (January 2005-December 2016). Their serum sodium and biochemical parameters were measured at baseline, along with 2-D echocardiographic assessments of left ventricular mass and ejection fraction. The primary endpoint was the association between hyponatremia and all-cause mortality (ACM) after a follow-up period of 24 months. Results:Mean age of patients was 60.61 ± 12.63 (SD) years; 65.1% were males, and type 2 diabetes mellitus (DM) was present in 71%. Baseline serum sodium was 138.00 (136, 140) (median and interquartile range). Hyponatremia (<135 meq/L) was present in 14.1%. After follow-up, 46 deaths had occurred. Multivariate Cox-proportional hazard model showed that type 2 DM, New York Heart Association (NYHA) class (III-IV vs I-II), age, and left ventricular mass index (LVMI) were significant and independent predictors of ACM, with HR 3.03 (95% CI; 1.13, 8.16) (P=0.028), HR 2.31 (95% CI; 1.11, 4.82) (P=0.026), HR 1.06 (95% CI; 1.03, 1.09) (P<0.001), and HR 1.01 (95% CI; 1.00, 1.02) (P=0.039), respectively. Estimated glomerular filtration rate (eGFR) was not a significant predictor. Kaplan-Meier survival analysis was used for the analysis of NYHA class and hyponatremia interactions and showed that hyponatremia had an association with poorer survival in patients with NYHA class III-IV rather than I-II (Log-rank test, P= 0.0009). Conclusion:Hyponatremia was a feature in CHF patients, and ACM was predicted by type 2 DM, NYHA class, age, and LVMI. Hyponatremia impact on survival was in patients with more advanced disease.

Project description:Diabetes and heart failure are closely related: patients with diabetes have an increased risk of developing heart failure and those with heart failure are at higher risk of developing diabetes. Furthermore, antidiabetic medications increase the risk of mortality and hospitalisation for heart failure in patients with and without pre-existing heart failure. When the two diseases are considered individually, heart failure has a much poorer prognosis than diabetes mellitus; therefore heart failure has to be a priority for treatment in patients presenting with the two conditions, and the diabetic patient with heart failure should be managed by the heart failure team. No specific randomised clinical trials have been conducted to test the effect of cardiovascular drugs in diabetic patients with heart failure, but a wealth of evidence suggests that all interventions effective at improving prognosis in patients with heart failure are equally beneficial in patients with and without diabetes. The negative effect of glucose-lowering agents in patients with heart failure or at increased risk of heart failure has become evident after the withdrawal of rosiglitazone, a thiazolidinedione, from the EU market due to evidence of increased risk of cardiovascular events and hospitalisations for heart failure. An important issue that remains unresolved is the optimal target level of glycated haemoglobin, as recent studies have demonstrated significant reductions in total mortality, morbidity and risk of heart failure despite achieving HbA1c levels similar to those observed in the UKPDS study conducted some decades ago. Meta-analyses showed that intensive glucose lowering is not associated with any significant reduction in cardiovascular risk but conversely results in a significant increase in heart failure risk. Different medications have different risk: benefit ratios in diabetic patients with heart failure; therefore, the heart failure team must judge the required intensity of glycaemic control, the type and dose of glucose lowering agents and any change in glucose-lowering therapy, according to the clinical conditions present.

Project description:BACKGROUND:Once-weekly exenatide (EQW) had a neutral effect on hospitalization for heart failure (HHF) in the EXSCEL study (Exenatide Study of Cardiovascular Event Lowering), with no differential treatment effect on major adverse cardiac events by baseline heart failure (HF) status. EQW's effects on secondary end points based on HHF status have not been reported. The objective was to explore the effects of EQW on secondary end points in patients with and without baseline HF and test the effects of EQW on recurrent HHF events. METHODS:The prespecified analysis of the randomized controlled EXSCEL trial, which enrolled patients with type 2 diabetes mellitus with and without additional cardiovascular disease, analyzed EQW effects on all-cause death, each major adverse cardiac event component, first HHF, and repeat HHF, by baseline HF status (regardless of ejection fraction). A subgroup analysis of the population stratified by preserved or reduced baseline ejection fraction was performed. RESULTS:Of 14 752 EXSCEL participants, 2389 (16.2%) had HF at baseline. Compared with those without HF at baseline, patients with preexisting HF were older, and more likely to be male and white, with a higher burden of other cardiovascular diseases. Overall, those assigned to EQW had a lower incidence of all-cause death (hazard ratio [HR], 0.86 [95% CI, 0.77-0.97]) and the composite outcome of all-cause death or HHF (HR, 0.89 [95% CI, 0.80-0.99]). When stratified by presence or absence of baseline HF, there was no observed reduction in all-cause death with EQW with baseline HF (HR, 1.05 [95% CI, 0.85-1.29]), while the risk of mortality was reduced with EQW in the no-HF group (HR, 0.79 [95% CI, 0.68-0.92]) with an interaction P value of 0.031. The reduction in all-cause death or HHF seen with EQW in patients without baseline HF (HR, 0.81 [95% CI, 0.71-0.93]) was not seen in patients with baseline HF (HR, 1.07 [95% CI, 0.89-1.29]; interaction P=0.015). First, plus recurrent, HHF was reduced in the exenatide group versus placebo (HR, 0.82 [95% CI, 0.68-0.99]; P=0.038). CONCLUSIONS:In EXSCEL, the use of EQW in patients with or without HF was well tolerated, but benefits of EQW on reduction in all-cause death and first hospitalization for HF were attenuated in patients with baseline HF. CLINICAL TRIAL REGISTRATION:https://www.clinicaltrials.gov. Unique identifier: NCT01144338.

Dataset Information

Clinical and Biomarker Predictors of Expanded Heart Failure Outcomes in Patients With Type 2 Diabetes Mellitus After a Recent Acute Coronary Syndrome: Insights From the EXAMINE Trial.

Publications

Clinical and Biomarker Predictors of Expanded Heart Failure Outcomes in Patients With Type 2 Diabetes Mellitus After a Recent Acute Coronary Syndrome: Insights From the EXAMINE Trial.

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