Effect of Aleglitazar on Cardiovascular Outcomes After Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus
Key result
Aleglitazar did not reduce the risk of cardiovascular death, nonfatal MI, or nonfatal stroke compared to placebo (HR 0.96; 95% CI 0.83-1.11; P=.57) and increased rates of safety end points.
Why the study?
Does aleglitazar reduce cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and a recent acute coronary syndrome?
Population
7,226 patients hospitalized for acute coronary syndrome with type 2 diabetes mellitus
Comparison
Aleglitazar 150 µg daily added to standard… vs Placebo daily added to standard medical therapy
Design
RCT, 1:1 ratio, double-blind, placebo-controlled
Follow-up
median 104 weeks
Authors
Discussion
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Implication
Aleglitazar should not be used in type 2 diabetes with recent ACS; challenges dual PPAR agonism for cardiovascular risk reduction.
Key Points
- To determine whether adding aleglitazar to standard medical therapy reduces cardiovascular morbidity and mortality among patients with type 2 diabetes mellitus and a recent acute coronary syndrome.
- Multicenter, phase 3, randomized, double-blind, placebo-controlled trial (AleCardio; NCT01042769) conducted across 720 hospitals in 26 countries.
- Enrolled 7,226 patients hospitalized for acute coronary syndrome with type 2 diabetes, randomized 1:1 to receive daily aleglitazar 150 µg or placebo with a median follow-up of 104 weeks.
- The primary efficacy end point (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) occurred in 9.5% (344 patients) in the aleglitazar group versus 10.0% (360 patients) in the placebo group (HR, 0.96; 95% CI, 0.83–1.11; P = .57).
- Aleglitazar significantly increased adverse safety events, including renal dysfunction (7.4% vs 2.7%, P < .001) and gastrointestinal hemorrhages (2.4% vs 1.7%, P = .03), leading to early trial termination for futility and harm.
Study Design
Type
RCT (n=7,226)
Blinding
Double-blind
Randomization
1:1
Multicenter
Yes
Structured PICO
Does aleglitazar reduce cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and a recent acute coronary syndrome?
P
Population
7,226 patients with type 2 diabetes and recent acute coronary syndrome, followed for a median of 104 weeks.
I
Intervention
Aleglitazar 150 µg daily added to standard medical therapy
C
Comparator
Placebo daily added to standard medical therapy
O
Outcome
Time to cardiovascular death, nonfatal myocardial infarction, or nonfatal strokecomposite
Main Result
Hazard Ratio: 0.96 (95% CI 0.83–1.11)
Absolute Event Rate: 9.5% vs 10%
p-value: p=.57
Aleglitazar does not reduce cardiovascular risk in patients with type 2 diabetes and recent ACS, and is associated with increased risks of gastrointestinal hemorrhage and renal dysfunction.
Cite This Study
Lincoff et al. (2014) conducted an RCT in Type 2 diabetes mellitus and recent acute coronary syndrome (n=7,226). Aleglitazar vs. Placebo was evaluated on time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR 0.96, 95% CI 0.83-1.11, p=.57). Aleglitazar did not reduce the risk of cardiovascular death, nonfatal MI, or nonfatal stroke compared to placebo (HR 0.96; 95% CI 0.83-1.11; P=.57) and increased rates of safety end points.