Re-evaluation of dipeptidyl peptidase-4 inhibitors in patients with heart failure and diabetes mellitus

OBJECTIVES:The question of whether dipeptidyl peptidase-4 inhibitors (DPP-4i) should be preferred as new glucose-lowering agents in heart failure is controversial. This studyaimed to evaluate the effects of DPP-4i treatment on all-cause mortality and cardiovascular outcomes in patients with heart failure. METHODS:We searched for available studies of DPP-4i therapy in heart failure and performed a pooled analysis. Outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), acute coronary syndrome, and acute myocardial infarction. RESULTS:Treatment with DPP-4i did not reduce the risk of all-cause death, cardiovascular death, or hospitalization for heart failure. Subgroup analyses showed that DPP-4i significantly reduced all-cause mortality in trials with > 40% female patients (OR 0.30, 95% CI [0.16, 0.58], P = 0.0003) and in trials with > 20% patients with heart failure with preserved ejection fraction (HFpEF) (OR 0.34, 95% CI [0.19, 0.60], P = 0.0003). Changes in LVEF and LVEDV showed no statistical differences between the 2 groups. Accordingly, DPP-4i did not alter the risk of acute coronary syndrome and acute myocardial infarction. CONCLUSIONS:DPP-4i may reduce all-cause mortality in heart failure patients in subgroups of women and HFpEF and has a high coronary safety profile.