0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Effect of Aleglitazar on Cardiovascular Outcomes After Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus:  The AleCardio Randomized Clinical Trial

A. Michael Lincoff, MD1; Jean-Claude Tardif, MD2; Gregory G. Schwartz, MD, PhD3; Stephen J. Nicholls, MBBS, PhD4; Lars Rydén, MD5; Bruce Neal, PhD6; Klas Malmberg, MD5,7; Hans Wedel, PhD8; John B. Buse, MD, PhD9; Robert R. Henry, MD10; Arlette Weichert, MD7; Ruth Cannata, RN1; Anders Svensson, MD7; Dietmar Volz, PhD7; Diederick E. Grobbee, MD, PhD11 ; for the AleCardio Investigators
[+] Author Affiliations
1Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio
2Montreal Heart Institute Coordinating Center, Université de Montréal, Montreal, Canada
3Veterans Affairs Medical Center and University of Colorado School of Medicine, Denver
4South Australian Health and Medical Research Institute, University of Adelaide, Adelaide
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6George Institute for Global Health, University of Sydney, Sydney, Australia
7F. Hoffman-La Roche Ltd, Basel, Switzerland
8Nordic School of Public Health, Frolunda, Sweden
9University of North Carolina School of Medicine, Chapel Hill
10University of California San Diego, San Diego
11Julius Center for Health Sciences and Primary Care and Julius Clinical, University Medical Center Utrecht, Utrecht, the Netherlands
JAMA. 2014;311(15):1515-1525. doi:10.1001/jama.2014.3321.
Text Size: A A A
Published online

Importance  No therapy directed against diabetes has been shown to unequivocally reduce the excess risk of cardiovascular complications. Aleglitazar is a dual agonist of peroxisome proliferator–activated receptors with insulin-sensitizing and glucose-lowering actions and favorable effects on lipid profiles.

Objective  To determine whether the addition of aleglitazar to standard medical therapy reduces cardiovascular morbidity and mortality among patients with type 2 diabetes mellitus and a recent acute coronary syndrome (ACS).

Design, Setting, and Participants  AleCardio was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted in 720 hospitals in 26 countries throughout North America, Latin America, Europe, and Asia-Pacific regions. The enrollment of 7226 patients hospitalized for ACS (myocardial infarction or unstable angina) with type 2 diabetes occurred between February 2010 and May 2012; treatment was planned to continue until patients were followed-up for at least 2.5 years and 950 primary end point events were positively adjudicated.

Interventions  Randomized in a 1:1 ratio to receive aleglitazar 150 µg or placebo daily.

Main Outcomes and Measures  The primary efficacy end point was time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Principal safety end points were hospitalization due to heart failure and changes in renal function.

Results  The trial was terminated on July 2, 2013, after a median follow-up of 104 weeks, upon recommendation of the data and safety monitoring board due to futility for efficacy at an unplanned interim analysis and increased rates of safety end points. A total of 3.1% of patients were lost to follow-up and 3.2% of patients withdrew consent. The primary end point occurred in 344 patients (9.5%) in the aleglitazar group and 360 patients (10.0%) in the placebo group (hazard ratio, 0.96 [95% CI, 0.83-1.11]; P = .57). Rates of serious adverse events, including heart failure (3.4% for aleglitazar vs 2.8% for placebo, P = .14), gastrointestinal hemorrhages (2.4% for aleglitazar vs 1.7% for placebo, P = .03), and renal dysfunction (7.4% for aleglitazar vs 2.7% for placebo, P < .001) were increased.

Conclusions and Relevance  Among patients with type 2 diabetes and recent ACS, use of aleglitazar did not reduce the risk of cardiovascular outcomes. These findings do not support the use of aleglitazar in this setting with a goal of reducing cardiovascular risk.

Trial Registration  clinicaltrials.gov Identifier: NCT01042769

Figures in this Article

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Figures

Place holder to copy figure label and caption
Figure 1.
CONSORT Diagram

Data were not collected regarding specific reasons for ineligibility.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Kaplan-Meier Estimates of Time to First Occurrence of Primary Efficacy End Point and Hospitalization for Heart Failure

Y-axis in blue indicates range from 0% to 10%. The primary efficacy end point was time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Mean Change in Glycated Hemoglobin, High- and Low-Density Lipoprotein Cholesterol, and Triglyceride Levels From Baseline Through 36 Months

Mean value at baseline: A, 7.8% for both placebo and aleglitazar; B, 41.8 mg/dL for placebo and 42.2 mg/dL for aleglitazar; C, 154 mg/dL for placebo and 152 mg/dL for aleglitazar; and D, 79.7 mg/dL for placebo and 78.9 mg/dL for aleglitazar. To convert high-density lipoprotein and low-density lipoprotein to millimoles per liter, multiply by 0.0259; triglycerides to millimoles per liter, multiply by 0.0113. Error bars indicate 95% CIs.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.
Mean Change in Weight and Creatinine Levels From Baseline Over Time

Mean value at baseline: A, 83.3 kg for placebo and 82.9 kg for aleglitazar; B, 0.97 mg/dL for placebo and 0.98 mg/dL for aleglitazar. Includes only patients who received at least 1 dose of study drug and according to drug actually received. B, Follow-up values were obtained 4 weeks after end of treatment. To convert creatinine to micromoles per liter, multiply by 88.4. Error bars indicate 95% CIs.

Graphic Jump Location

Tables

References

Letters

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 1

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs
JAMAevidence.com

The Rational Clinical Examination
Evidence Summary and Review 2

The Rational Clinical Examination
Multivariate Findings for ACI Syndromes

brightcove.createExperiences();