Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial
Autor: | Diego Bellido Guerrero, Melchor Alpizar, Marco Vugman Wainstein, Esther Sanz-Girgas, Kamal Sharma, Vincent Maher, Zbigniew Pijanowski, Laszlo Koranyi, Audes Feitosa, Stephen Nicholls, Leszek Gromadziński, Michel GALINIER, Sang-Hyun Kim, Rakesh Sahay, Kurt Boman, Bruce Neal, John Buse, Piotr Ponikowski, Xavier Garcia-Moll, Robert Welsh, Carmen Lab, Francesco Cosentino, Team3 Carmen |
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Přispěvatelé: | Lincoff, A. Michael, Tardif, Jean Claude, Schwartz, Gregory G., Nicholls, Stephen J., Rydén, Lar, Neal, Bruce, Malmberg, Kla, Wedel, Han, Buse, John B., Henry, Robert R., Weichert, Arlette, Cannata, Ruth, Svensson, Ander, Volz, Dietmar, Grobbee, Diederick E., PERRONE FILARDI, Pasquale |
Rok vydání: | 2014 |
Předmět: |
Male
Risk Peroxisome Proliferator-Activated Receptor medicine.medical_specialty Acute coronary syndrome Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] Peroxisome Proliferator-Activated Receptors Myocardial Infarction Acute Coronary Syndrome Aged Diabetes Mellitus Type 2 Double-Blind Method Female Humans Hypoglycemic Agents Kidney Middle Aged Oxazoles Stroke Survival Analysis Thiophenes Treatment Outcome Medicine (all) Type 2 diabetes Placebo Oxazole law.invention chemistry.chemical_compound Randomized controlled trial Thiophene law Internal medicine medicine Clinical endpoint Aleglitazar Hypoglycemic Agent business.industry Unstable angina General Medicine medicine.disease Interim analysis chemistry Physical therapy Survival Analysi business Human |
Zdroj: | Jama : Journal of the American Medical Association, 311, 1515-25 Jama : Journal of the American Medical Association, 311, 15, pp. 1515-25 |
ISSN: | 0104-2769 0098-7484 |
Popis: | Item does not contain fulltext 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 microg 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. |
Databáze: | OpenAIRE |
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