Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome.
BACKGROUND
Despite contemporary therapies for acute coronary syndrome (ACS), morbidity and mortality remain high. Low levels of high-density lipoprotein (HDL) cholesterol are common among patients with ACS and may contribute to ongoing risk. Strategies that raise levels of HDL cholesterol, such as inhibition of cholesterol ester transfer protein (CETP), might reduce risk after ACS. Dal-OUTCOMES is a multicenter, randomized, double-blind, placebo-controlled trial designed to test the hypothesis that CETP inhibition with dalcetrapib reduces cardiovascular morbidity and mortality in patients with recent ACS.


METHODS
The study will randomize approximately 15,600 patients to receive daily doses of dalcetrapib 600 mg or matching placebo, beginning 4 to 12 weeks after an index ACS event. There are no prespecified boundaries for HDL cholesterol levels at entry. Other elements of care, including management of low-density lipoprotein cholesterol, are to follow best evidence-based practice. The primary efficacy measure is time to first occurrence of coronary heart disease death, nonfatal acute myocardial infarction, unstable angina requiring hospital admission, resuscitated cardiac arrest, or atherothrombotic stroke. The trial will continue until 1,600 primary end point events have occurred, all evaluable subjects have been followed for at least 2 years, and 80% of evaluable subjects have been followed for at least 2.5 years.


CONCLUSIONS
Dal-OUTCOMES will determine whether CETP inhibition with dalcetrapib, added to current evidence-based care, reduces cardiovascular morbidity and mortality after ACS.
Schwartz
Gregory G
GG
VA Medical Center and University of Colorado, Denver, CO 80220, USA. gregory.schwartz@va.gov
Olsson
Anders G
AG
Ballantyne
Christie M
CM
Barter
Phillip J
PJ
Holme
Ingar M
IM
Kallend
David
D
Leiter
Lawrence A
LA
Leitersdorf
Eran
E
McMurray
John J V
JJ
Shah
Prediman K
PK
Tardif
Jean-Claude
JC
Chaitman
Bernard R
BR
Duttlinger-Maddux
Regina
R
Mathieson
John
J
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000577:Amides; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004952:Esters; D006801:Humans; D012107:Research Design; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*
D000577:Amides; D000924:Anticholesteremic Agents; D004952:Esters; D013438:Sulfhydryl Compounds; C411602:dalcetrapib