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

Abhinav Sharma, Christopher P. Cannon, William B. White, Yuyin Liu, George L. Bakris, William Cushman, Faiez Zannad

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article numbere007649
JournalJournal of the American Heart Association
Volume7
Issue number11
DOIs
StatePublished - Jun 1 2018

Fingerprint

Dipeptidyl Peptidase 4
Acute Coronary Syndrome
Type 2 Diabetes Mellitus
Hospitalization
Heart Failure
Confidence Intervals
Stroke
Myocardial Infarction
Hypoglycemic Agents
Standard of Care
Random Allocation
Placebos
Demography
dipeptidase
Safety
alogliptin
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

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. / Sharma, Abhinav; Cannon, Christopher P.; White, William B.; Liu, Yuyin; Bakris, George L.; Cushman, William; Zannad, Faiez.

In: Journal of the American Heart Association, Vol. 7, No. 11, e007649, 01.06.2018.

Research output: Contribution to journalArticle

@article{79081904db0842dea747192b2520c729,
title = "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",
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.",
author = "Abhinav Sharma and Cannon, {Christopher P.} and White, {William B.} and Yuyin Liu and Bakris, {George L.} and William Cushman and Faiez Zannad",
year = "2018",
month = "6",
day = "1",
doi = "10.1161/JAHA.117.007649",
language = "English (US)",
volume = "7",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - Early and chronic dipeptidyl-peptidase-IV inhibition and cardiovascular events in patients with type 2 diabetes mellitus after an acute coronary syndrome

T2 - A landmark analysis of the EXAMINE trial

AU - Sharma, Abhinav

AU - Cannon, Christopher P.

AU - White, William B.

AU - Liu, Yuyin

AU - Bakris, George L.

AU - Cushman, William

AU - Zannad, Faiez

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85047974112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047974112&partnerID=8YFLogxK

U2 - 10.1161/JAHA.117.007649

DO - 10.1161/JAHA.117.007649

M3 - Article

VL - 7

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 11

M1 - e007649

ER -