Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus

Lincoff AM, Tardiff J-C, Schwartz GG, et al; for the AleCardio Investigators. Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus. The AleCardio randomized clinical trial. JAMA.. 2014. doi:10.1001/jama.2014.3321.

AleCardio, the first large-scale CV outcomes trial of a dual PPAR activator, failed to meet its primary efficacy endpoint of time to first occurrence of any part of the composite of CV mortality, nonfatal MI, or nonfatal stroke. The AleCardio trial looked at aleglitazar, a dual PPAR-α and PPAR-γ agonist with insulin-sensitizing and glucose-lowering effects, as well as favorable metabolic and lipid effects.

This Phase 3, randomized, double-blind, placebo-controlled superiority study assessed whether treatment with aleglitazar would reduce cardiovascular morbidity and mortality among patients with type 2 diabetes and recent acute coronary syndrome (ACS). A total of 7,226 subjects were randomized to aleglitazar 150 µg QD (n=3,616) or placebo (n=3,610); all continued on guideline-based treatment for ACS, diabetes, and CHD risk factors. AleCardio was terminated early in July 2013 for futility and a higher than expected incidence of adverse events among aleglitazar-treated patients. Median follow up was 104 weeks; the trial was originally planned for 2.5 years and until 950 primary endpoints were adjudicated.

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AleCardio Design 

AleCardio: Design

Primary endpoint
The study did not meet its primary efficacy endpoint: the primary endpoint occurred among 9.5% of patients in the aleglitazar group and 10.0% in the placebo group (HR, 0.96 [95% CI, 0.83-1.11]; P=0.57).

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AleCardio Time to First Occurence of Any Part of Composite CV Mortality Nonfatal MI or Nonfatal Stroke With Aleglitazar Vs Placebo 

AleCardio: Time to First Occurrence of Any Part of the Composite of
CV Mortality, Nonfatal MI, or Nonfatal Stroke with Aleglitazar Vs Placebo

A1C reductions
Subjects who received aleglitazar had significantly lower A1C compared with subjects in the placebo group. In addition, 86% of aleglitazar-treated patients had achieved A1C <7% by the end of the treatment period compared with 71% in the placebo group (P<0.001).

Safety findings
Safety endpoints were hospitalization due to heart failure and changes in renal function. Aleglitazar-treated subjects had a higher rate of both safety endpoints, as well as gastrointestinal hemorrhages.

  % of subjects, aleglitazar vs placebo
HR (95% CI)
P value
Hospitalization due to  
heart failure*
3.4% vs 2.8%
1.22 (0.94-1.59)
P=0.14
Changes in
renal function*
7.4% vs 2.7%
2.85 (2.25-3.60)
P<0.001
GI hemorrhage 2.4% vs 1.7%
1.44 (1.03-2.00)
P=0.03

*Primary safety endpoint

Incidence of ≥1 hypoglycemic event was significantly greater among aleglitazar-treated subjects: 17% vs 11% treated with placebo; HR, 1.60 (95% CI, 1.41-1.82); P<0.001. Numerically more subjects who received aleglitazar also experienced bone fracture.

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AleCardio Aleglitazar Safety Vs Placebo 

AleCardio: Aleglitazar Safety Vs Placebo

Aleglitazar is an investigational compound that is not approved for use by the U.S. Food and Drug Administration.

CHD=coronary heart disease; MI=myocardial infarction 

 

  

April 2014

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

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Last Modified: 8/4/2014