Associations of dipeptidyl peptidase‐4 inhibitors with mortality in hospitalized heart failure patients with diabetes mellitus

Abstract

BackgroundHeart failure (HF) and diabetes mellitus (DM) often co‐exist. Treatment of DM in HF patients is challenging because some therapies for DM are contraindicated in HF. Although previous experimental studies have reported that dipeptidyl peptidase‐4 (DPP‐4) inhibitors improve cardiovascular function, whether DPP‐4 inhibition improves mortality of HF patients with DM remains unclear. Therefore, we examined the impact of DPP‐4 inhibition on mortality in hospitalized HF patients using propensity score analyses.Methods and resultsWe performed observational study analysed by propensity score method with 962 hospitalized HF patients. Of these patients, 293 (30.5%) had DM, and 122 of these DM patients were treated with DPP‐4 inhibitors. Propensity scores for treatment with DPP‐4 inhibitors were estimated for each patient by logistic regression with clinically relevant baseline variables. The propensity‐matched 1:1 cohorts were assessed based on propensity scores (DPP‐4 inhibitors, n = 83, and non‐DPP‐4 inhibitors, n = 83). Kaplan–Meier analysis in the propensity score‐matched cohort demonstrated that cardiac and all‐cause mortality was significantly lower in the DPP‐4 inhibitor group than in the non‐DPP‐4 inhibitor group (cardiac mortality: 4.8% vs. 18.1%, P = 0.015; all‐cause mortality: 14.5% vs. 41.0%, P = 0.003, by a log‐rank test). In the multivariable Cox proportional hazard analyses, after adjusting for other potential confounding factors, the use of DPP‐4 inhibitors was an independent predictor of all‐cause mortality (pre‐matched cohort: hazard ratio 0.467, P = 0.010; post‐matched cohort: hazard ratio 0.370, P = 0.003) in HF patients with DM.ConclusionsOur data suggest that DPP‐4 inhibitors may improve cardiac and all‐cause mortality in hospitalized HF patients with DM.

Diabetes Mellitus and Heart Failure

“…Retrospective propensity scoreematched analysis of patients with heart failure and diabetes receiving DPP-4 inhibitors or other glucoselowering drugs found DPP-4 inhibitor treatment to be associated with reduced cardiac and all-cause mortality. 76 Further, a large retrospective analysis including 78,553 new saxagliptin or 298,124 new sitagliptin users reported lower risk for heart failure hospitalization with DPP-4 inhibitor treatment in comparison with pioglitazone, sulfonylureas, or insulin treatment. 77 In addition, neither DPP-4 inhibitors nor GLP-1 receptor agonists (GLP-1 RAs) were associated with increased heart failure hospitalization in a retrospective cohort analysis of 1,499,650 patients with diabetes, including 79,800 with a history of heart failure.…”

Regional differences in heart failure hospitalizations, mortality, and readmissions in Slovenia 2004–2012

“…In Slovenia, general trend of reducing HF mortality could be explained by the reduction of CV risk factors and improvement in the care of HF patients . Even though the adherence to guidelines in the managing of HF is improving, there is still room for improvement and better detection of patients at risk …”

Empagliflozin, calcium, and SGLT1/2 receptor affinity: another piece of the puzzle

“…Importantly, reductions in the risks of CV death with empagliflozin were consistent across the two doses used and the categories of baseline HbA1c and therefore occurred irrespective of glycaemic control . The results of the EMPA‐REG OUTCOME trial triggered a lively discussion on mechanisms contributing to the beneficial effects on HF outcomes …”

“…2 The results of the EMPA-REG OUTCOME trial triggered a lively discussion on mechanisms contributing to the beneficial effects on HF outcomes. [3][4][5][6][7] So far, the 'magic bullet' responsible for the favourable HF outcomes of empaglifozin has not yet been identified, and most likely, there is no such single mechanism of action that can explain the benefits in its entirety. Promising mechanisms under discussion refer to an improved oxygen supply to the failing heart via an increase of the haematocrit, a metabolic shift towards the consumption of more ketone bodies when other fuels like glucose fail in HF, an unloading of the kidney with a reduction of glomerular pressure and reduced oxygen consumption in the proximal tubule, as well as natriuresis and volume depletion.…”