Search

Background: Heart failure (HF) is a growing public health problem and ischemic heart disease is an important risk factor. Understanding the epidemiology of HF in patients with atherosclerosis may help identify subgroups at greater risk who have the potential to derive greater benefit from preventive strategies. Methods and Results: The TRA 2°P‐TIMI 50 trial randomized 26,449 patients with stable atherosclerosis to the antiplatelet agent vorapaxar versus placebo. Hospitalization for HF (HHF) endpoints were adjudicated from serious adverse events by blinded structured review using established definitions. HHF incidence was estimated using Kaplan–Meier analysis. Independent predictors of HHF risk were identified using multivariable logistic regression. The effect of vorapaxar on HHF risk was explored using Cox regression. The estimated incidence of HHF at 3 years was 1.6%. Independent predictors of HHF included prior HF (adjusted odds ratio [adj‐OR]: 8.31; 95% confidence interval [CI]: 6.56–10.54), age (adj‐OR [per 10 years]: 1.67; 95% CI: 1.47–1.89), type 2 diabetes mellitus (T2DM; adj‐OR: 2.55; 95% CI: 2.01–3.24), polyvascular disease (two‐territory disease, adj‐OR: 1.89; 95% CI: 1.46–2.44; three‐territory disease, adj‐OR: 2.68; 95% CI: 1.94–3.70), chronic kidney disease (CKD; adj‐OR: 1.65; 95% CI: 1.30–2.11), body mass index (BMI; adj‐OR [per 5 kg/m2]: 1.15; 95% CI: 1.03–1.27), prior myocardial infarction (MI) (adj‐OR: 1.35; 95% CI: 1.03–1.78), and hypertension (adj‐OR: 1.44; 95% CI: 1.02–2.04). Patients who experienced HHF during follow‐up had higher rates of subsequent rehospitalization and death. Vorapaxar did not modify the risk of HHF. Conclusions: In patients with stable atherosclerosis, prior HF, age, T2DM, polyvascular disease, CKD, BMI, prior MI, and hypertension are important predictors of HHF risk. [ABSTRACT FROM AUTHOR]

Aims: Dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus in DECLARE‐TIMI 58. We hypothesized that baseline N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity troponin T (hsTnT) levels would help identify patients who are at higher baseline risk and we describe the treatment effects of dapagliflozin in patients according to their baseline NT‐proBNP and hsTnT levels. Methods and results: This was a pre‐specified biomarker study from DECLARE‐TIMI 58, a randomized, double‐blind, placebo‐controlled CV outcomes trial of dapagliflozin. Baseline NT‐proBNP and hsTnT levels were measured in the TIMI Clinical Trials Laboratory in 14 565 patients. Among the included patients, 9143 patients (62.8%) were male, 1464 (10.1%) had a history of heart failure and the mean age was 63.9 years. The median baseline NT‐proBNP and hsTnT levels were 75 pg/mL [interquartile range (IQR) 35–165] and 10.2 pg/mL (IQR 6.9–15.5), respectively. Patients with higher NT‐proBNP and hsTnT quartiles had higher rates of CV death/HHF (Q4 vs. Q1: NT‐proBNP: 4‐year Kaplan–Meier event rates 13.7% vs. 1.0%; hsTnT: 11.8% vs. 1.4%; P‐trend <0.001). Dapagliflozin consistently reduced the relative risk of CV death/HHF regardless of baseline NT‐proBNP (P‐interaction 0.72) or hsTnT quartiles (P‐interaction 0.93). Given their higher baseline risk, patients with NT‐proBNP and/or hsTnT levels above the median derived larger absolute risk reductions with dapagliflozin (NT‐proBNP 1.9% vs. 0%, P‐interaction 0.010; hsTnT 1.8% vs. 0.1%, P‐interaction 0.026). Conclusion: Patients with type 2 diabetes mellitus and higher NT‐proBNP or hsTnT levels are at increased risk of CV death and HHF. Dapagliflozin reduced the relative risk of CV death/HHF irrespective of NT‐proBNP and hsTnT levels, with greater absolute risk reductions seen in patients with higher baseline biomarker levels. [ABSTRACT FROM AUTHOR]

Aim: To assess the associations between baseline glucose‐lowering agents (GLAs) and cardiorenal outcomes with dapagliflozin versus placebo in the DECLARE‐TIMI 58 study. Materials and methods: DECLARE‐TIMI 58 assessed the cardiorenal outcomes of dapagliflozin versus placebo in patients with type 2 diabetes. This post hoc analysis elaborates the efficacy and safety outcomes by baseline GLA for treatment effect and GLA‐based treatment interaction. Results: At baseline, 14 068 patients (82.0%) used metformin, 7322 (42.7%) sulphonylureas, 2888 (16.8%) dipeptidyl peptidase‐4 inhibitors, 750 (4.4%) glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and 7013 (40.9%) insulin. Dapagliflozin reduced the composite of cardiovascular death (CVD) and hospitalization for heart failure (HHF) versus placebo regardless of baseline GLA, with greater benefit in the small group of patients with baseline use of GLP‐1 RAs (HR [95% CI] 0.37 [0.18, 0.78] vs. 0.86 [0.75, 0.98] in GLP‐1 RA users vs. non‐users, Pinteraction =.03). The overall HR for major adverse cardiovascular events (CVD, myocardial infarction or ischaemic stroke) was 0.93 (95% CI 0.84, 1.03) with dapagliflozin versus placebo, with no interaction by baseline GLA (Pinteraction >.05). The renal‐specific outcome was reduced with dapagliflozin versus placebo in the overall cohort (HR [95%CI] 0.53[0.43‐0.66]), with no interaction by baseline GLA (Pinteraction >.05). All of these outcomes were similar in those with versus those without baseline metformin use. Conclusions: The effects of dapagliflozin on cardiorenal outcomes were generally consistent regardless of baseline GLA, with consistent benefits regardless of baseline metformin use. The potential clinical benefit of combining sodium‐glucose co‐transporter‐2 inhibitors with GLP‐1 RAs, given some evidence of cardiovascular risk reduction with both classes, should be explored further. [ABSTRACT FROM AUTHOR]