Angiotensin-converting enzyme inhibitor use and major cardiovascular outcomes in type 2 diabetes mellitus treated with the dipeptidyl peptidase 4 inhibitor alogliptin

William B. White, Craig A. Wilson, George L. Bakris, Richard M. Bergenstal, Christopher P. Cannon, William Cushman, Simon K. Heller, Cyrus R. Mehta, Steven E. Nissen, Faiez Zannad, Stuart Kupfer

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of high-dose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62%) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4% versus 11.8%; hazard ratio, 0.97; 95% confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8% of patients on alogliptin versus 7.2% on placebo (hazard ratio, 0.93; 95% confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors.

Original languageEnglish (US)
Pages (from-to)606-613
Number of pages8
JournalHypertension
Volume68
Issue number3
DOIs
StatePublished - Sep 1 2016

Fingerprint

Dipeptidyl-Peptidase IV Inhibitors
Angiotensin-Converting Enzyme Inhibitors
Type 2 Diabetes Mellitus
Placebos
Confidence Intervals
Heart Failure
Stroke
Myocardial Infarction
Dipeptidyl Peptidase 4
Mortality
alogliptin
Sympathetic Nervous System
Peptidyl-Dipeptidase A
Standard of Care
Acute Coronary Syndrome
Proportional Hazards Models
Hypoglycemic Agents
Coronary Disease
Heart Rate
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Angiotensin-converting enzyme inhibitor use and major cardiovascular outcomes in type 2 diabetes mellitus treated with the dipeptidyl peptidase 4 inhibitor alogliptin. / White, William B.; Wilson, Craig A.; Bakris, George L.; Bergenstal, Richard M.; Cannon, Christopher P.; Cushman, William; Heller, Simon K.; Mehta, Cyrus R.; Nissen, Steven E.; Zannad, Faiez; Kupfer, Stuart.

In: Hypertension, Vol. 68, No. 3, 01.09.2016, p. 606-613.

Research output: Contribution to journalArticle

White, WB, Wilson, CA, Bakris, GL, Bergenstal, RM, Cannon, CP, Cushman, W, Heller, SK, Mehta, CR, Nissen, SE, Zannad, F & Kupfer, S 2016, 'Angiotensin-converting enzyme inhibitor use and major cardiovascular outcomes in type 2 diabetes mellitus treated with the dipeptidyl peptidase 4 inhibitor alogliptin', Hypertension, vol. 68, no. 3, pp. 606-613. https://doi.org/10.1161/HYPERTENSIONAHA.116.07797
White, William B. ; Wilson, Craig A. ; Bakris, George L. ; Bergenstal, Richard M. ; Cannon, Christopher P. ; Cushman, William ; Heller, Simon K. ; Mehta, Cyrus R. ; Nissen, Steven E. ; Zannad, Faiez ; Kupfer, Stuart. / Angiotensin-converting enzyme inhibitor use and major cardiovascular outcomes in type 2 diabetes mellitus treated with the dipeptidyl peptidase 4 inhibitor alogliptin. In: Hypertension. 2016 ; Vol. 68, No. 3. pp. 606-613.
@article{0bb2bbf3568b4f2e8a155da86d420ae5,
title = "Angiotensin-converting enzyme inhibitor use and major cardiovascular outcomes in type 2 diabetes mellitus treated with the dipeptidyl peptidase 4 inhibitor alogliptin",
abstract = "Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of high-dose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62{\%}) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4{\%} versus 11.8{\%}; hazard ratio, 0.97; 95{\%} confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2{\%} versus 11.9{\%}; hazard ratio, 0.94; 95{\%} confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8{\%} of patients on alogliptin versus 7.2{\%} on placebo (hazard ratio, 0.93; 95{\%} confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors.",
author = "White, {William B.} and Wilson, {Craig A.} and Bakris, {George L.} and Bergenstal, {Richard M.} and Cannon, {Christopher P.} and William Cushman and Heller, {Simon K.} and Mehta, {Cyrus R.} and Nissen, {Steven E.} and Faiez Zannad and Stuart Kupfer",
year = "2016",
month = "9",
day = "1",
doi = "10.1161/HYPERTENSIONAHA.116.07797",
language = "English (US)",
volume = "68",
pages = "606--613",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Angiotensin-converting enzyme inhibitor use and major cardiovascular outcomes in type 2 diabetes mellitus treated with the dipeptidyl peptidase 4 inhibitor alogliptin

AU - White, William B.

AU - Wilson, Craig A.

AU - Bakris, George L.

AU - Bergenstal, Richard M.

AU - Cannon, Christopher P.

AU - Cushman, William

AU - Heller, Simon K.

AU - Mehta, Cyrus R.

AU - Nissen, Steven E.

AU - Zannad, Faiez

AU - Kupfer, Stuart

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of high-dose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62%) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4% versus 11.8%; hazard ratio, 0.97; 95% confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8% of patients on alogliptin versus 7.2% on placebo (hazard ratio, 0.93; 95% confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors.

AB - Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of high-dose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62%) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4% versus 11.8%; hazard ratio, 0.97; 95% confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8% of patients on alogliptin versus 7.2% on placebo (hazard ratio, 0.93; 95% confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors.

UR - http://www.scopus.com/inward/record.url?scp=84980343935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84980343935&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.116.07797

DO - 10.1161/HYPERTENSIONAHA.116.07797

M3 - Article

VL - 68

SP - 606

EP - 613

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 3

ER -