Early and Chronic Dipeptidyl-Peptidase-IV Inhibition and Cardiovascular Events in Patients With Type 2 Diabetes Mellitus After an Acute Coronary Syndrome: A Landmark Analysis of the EXAMINE Trial

J Am Heart Assoc. 2018 May 16;7(11):e007649. doi: 10.1161/JAHA.117.007649.

Abstract

Background: Antihyperglycemic therapies may increase the risk of cardiovascular events including hospitalization for heart failure. There is a paucity of data evaluating the cardiovascular safety of antihyperglycemic therapies in the high-risk period following an acute coronary syndrome (ACS).

Methods and results: The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial randomized 5380 patients who were 15 to 90 days post ACS to the dipeptidyl dipeptidase-IV (DPP-IV) inhibitor alogliptin versus placebo; mean follow-up was 18 months. Using a landmark analysis, we assessed the (1) burden of cardiovascular events from randomization to 6 months (early period) and from 6 months to the end of follow-up (late period) and (2) the risk of cardiovascular events associated with early (up to 6 months) and chronic (6 months to end of follow-up) DPP-IV inhibition with alogliptin. Patients with early versus late events had similar baseline demographic profiles. Overall, 42.1% of the composite of cardiovascular death/myocardial infarction/stroke and 47.5% of hospitalization for heart failure occurred in the early period. Early DPP-IV inhibition did not increase the risk of early cardiovascular death/myocardial infarction/stroke (hazard ratio 0.96, 95% confidence interval, 0.76-1.21) or hospitalization for heart failure (1.23, 95% confidence interval, 0.84-1.82). Similarly, chronic DPP-IV inhibition did not increase the risk of late cardiovascular death/myocardial infarction/stroke (hazard ratio 1.03, 95% confidence interval, 0.89-1.26) or hospitalization for heart failure (hazard ratio 1.02, 95% confidence interval, 0.85-1.22).

Conclusions: Early after an ACS, patients with type 2 diabetes mellitus experience a significant burden of HF events and recurrent ACS. DPP-IV inhibition with alogliptin appears to be safe even in the high-risk period following an ACS.

Trial registration: ClinicalTrials.gov NCT00968708.

Keywords: acute coronary syndrome; alogliptin; diabetes mellitus; dipeptidyl dipeptidase‐4 inhibitor; medical therapy; medication.

Publication types

  • Equivalence Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / epidemiology*
  • Acute Coronary Syndrome / mortality
  • Aged
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Double-Blind Method
  • Female
  • Heart Failure / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / therapy
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Stroke / epidemiology
  • Time Factors
  • Treatment Outcome
  • Uracil / adverse effects
  • Uracil / analogs & derivatives*
  • Uracil / therapeutic use

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Piperidines
  • Uracil
  • alogliptin

Associated data

  • ClinicalTrials.gov/NCT00968708