PMID- 32916607
OWN - NLM
STAT- MEDLINE
DCOM- 20201208
LR  - 20201214
IS  - 1097-6744 (Electronic)
IS  - 0002-8703 (Linking)
VI  - 229
DP  - 2020 Nov
TI  - Timing of randomization after an acute coronary syndrome in patients with type 2 
      diabetes mellitus.
PG  - 40-51
LID - S0002-8703(20)30220-9 [pii]
LID - 10.1016/j.ahj.2020.07.014 [doi]
AB  - BACKGROUND: The timing of enrolment following an acute coronary syndrome (ACS) 
      may influence cardiovascular (CV) outcomes and potentially treatment effect in 
      clinical trials. Understanding the timing and type of clinical events after an 
      ACS will allow for clinicians to better tailor evidence-based treatments to 
      optimize therapeutic effect. Using a large contemporary trial in patients with 
      type 2 diabetes mellitus (T2DM) post-ACS, we examined the impact of timing of 
      enrolment on subsequent CV outcomes. METHODS: EXAMINE was a randomized trial of 
      alogliptin versus placebo in 5,380 patients with T2DM and a recent ACS from 
      October 2009 to March 2013. The primary outcome was a composite of CV death, 
      nonfatal myocardial infarction (MI), or nonfatal stroke. The median follow-up was 
      18 months. In this post hoc analysis, we examined the occurrence of subsequent CV 
      events by timing of enrollment divided by tertiles of time from ACS to 
      randomization: 8-34, 35-56, and 57-141 days. RESULTS: Patients randomized early 
      (compared to the latest times) had less comorbidities at baseline including a 
      history of heart failure (HF; 24.7% vs 33.0%), prior coronary artery bypass graft 
      (9.6% vs 15.9%), or atrial fibrillation (5.9% vs 9.4%). Despite the reduced 
      comorbidity burden, the risk of the primary outcome was highest in patients 
      randomized early compared to the latest time (adjusted hazard ratio 1.47; 95% CI 
      1.21-1.74). Similarly, patients randomized early had an increased risk of 
      recurrent MI (adjusted hazard ratio 1.51; 95% CI 1.17-1.96) and HF 
      hospitalization (1.49; 95% CI 1.05-2.10). CONCLUSIONS: In a contemporary cohort 
      of T2DM with a recent ACS, the risk for recurrent CV events including MI and HF 
      hospitalization is elevated early after an ACS. Given the emergence of 
      antihyperglycemic therapies that reduce the risk of MI and HF among patients with 
      T2DM at high CV risk, future studies evaluating the initiation of these therapies 
      in the early period following an ACS are warranted given the large burden of 
      potentially modifiable CV events.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Elharram, Malik
AU  - Elharram M
AD  - McGill University Health Centre, Montreal, Quebec, Canada.
FAU - Sharma, Abhinav
AU  - Sharma A
AD  - McGill University Health Centre, Montreal, Quebec, Canada; DREAM-CV Lab, McGill 
      University Health Centre, Montreal, Quebec, Canada. Electronic address: 
      Abhinav.sharma@mcgill.ca.
FAU - White, William
AU  - White W
AD  - University of Connecticut, Farmington, CT.
FAU - Bakris, George
AU  - Bakris G
AD  - University of Chicago Pritzker School of Medicine, Chicago, IL.
FAU - Rossignol, Patrick
AU  - Rossignol P
AD  - Universite de Lorraine, Inserm, Centre d'Investigations cliniques-plurithematique 
      1433, Inserm U1116; CHRU Nancy; F-CRIN INI-CRCT network, Nancy, France.
FAU - Mehta, Cyrus
AU  - Mehta C
AD  - Harvard T.H. Chan School of Public Health, Cambridge, MA; Cytel Corporation, 
      Cambridge, MA, USA.
FAU - Ferreira, Joao Pedro
AU  - Ferreira JP
AD  - Universite de Lorraine, Inserm, Centre d'Investigations cliniques-plurithematique 
      1433, Inserm U1116; CHRU Nancy; F-CRIN INI-CRCT network, Nancy, France.
FAU - Zannad, Faiez
AU  - Zannad F
AD  - Universite de Lorraine, Inserm, Centre d'Investigations cliniques-plurithematique 
      1433, Inserm U1116; CHRU Nancy; F-CRIN INI-CRCT network, Nancy, France.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200806
PL  - United States
TA  - Am Heart J
JT  - American heart journal
JID - 0370465
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Piperidines)
RN  - 56HH86ZVCT (Uracil)
RN  - JHC049LO86 (alogliptin)
SB  - IM
MH  - *Acute Coronary Syndrome/complications/therapy
MH  - Comorbidity
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy
MH  - Evidence-Based Practice/methods/standards
MH  - Female
MH  - Heart Disease Risk Factors
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - *Myocardial Infarction/diagnosis/etiology/mortality
MH  - Outcome and Process Assessment, Health Care
MH  - *Patient Selection
MH  - *Piperidines/administration & dosage/adverse effects
MH  - *Random Allocation
MH  - Risk Assessment/methods/statistics & numerical data
MH  - *Stroke/diagnosis/etiology/mortality
MH  - *Time Factors
MH  - Uracil/administration & dosage/adverse effects/*analogs & derivatives
EDAT- 2020/09/12 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/09/11 20:22
PHST- 2020/04/24 00:00 [received]
PHST- 2020/07/18 00:00 [accepted]
PHST- 2020/09/12 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/09/11 20:22 [entrez]
AID - S0002-8703(20)30220-9 [pii]
AID - 10.1016/j.ahj.2020.07.014 [doi]
PST - ppublish
SO  - Am Heart J. 2020 Nov;229:40-51. doi: 10.1016/j.ahj.2020.07.014. Epub 2020 Aug 6.