Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhi Show more
Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome. In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg daily or placebo, beginning 4-12 weeks after an acute coronary syndrome. Absence of diabetes at baseline was based on medical history, no use of antihyperglycemic medication, and hemoglobin A At baseline, 10,645 patients (67% of the trial cohort) did not have diabetes. During a median follow-up of 30 months, incident diabetes was identified in 403 of 5,326 patients (7.6%) assigned to dalcetrapib and in 516 of 5,319 (9.7%) assigned to placebo, corresponding to absolute risk reduction of 2.1%, hazard ratio of 0.77 (95% CI 0.68-0.88; In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib. Show less
Cholesteryl ester transfer protein (CETP) facilitates exchange of triglycerides and cholesteryl ester between high-density lipoprotein (HDL) and apolipoprotein B100-containing lipoproteins. Evidence f Show more
Cholesteryl ester transfer protein (CETP) facilitates exchange of triglycerides and cholesteryl ester between high-density lipoprotein (HDL) and apolipoprotein B100-containing lipoproteins. Evidence from genetic studies that variants in the CETP gene were associated with higher blood HDL cholesterol, lower low-density lipoprotein cholesterol, and lower risk of coronary heart disease suggested that pharmacological inhibition of CETP may be beneficial. To date, 4 CETP inhibitors have entered phase 3 cardiovascular outcome trials. Torcetrapib was withdrawn due to unanticipated off-target effects that increased risk of death, and major trials of dalcetrapib and evacetrapib were terminated early for futility. In the 30,000-patient REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification) trial, anacetrapib doubled HDL cholesterol, reduced non-HDL cholesterol by 17 mg/dl (0.44 mmol/l), and reduced major vascular events by 9% over 4 years, but anaceptrapib was found to accumulate in adipose tissue, and regulatory approval is not being sought. Therefore, despite considerable initial promise, CETP inhibition provides insufficient cardiovascular benefit for routine use. Show less