The AIM-HIGH Study was an investigator-initiated trial that was approved and sponsored by the National Heart, Lung, and Blood Institute (NHLBI). The design and organization of the trial and the baseline data have been described previously. Abbott Laboratories provided additional support from an unrestricted research grant. The extended-release niacin (Niaspan), the matching placebo
, and the ezetimibe were provided by Abbott Laboratories; Merck donated the simvastatin. The companies that provided financial support or products had no role in the oversight or design of the study or in the analysis or interpretation of the data. The study protocol, available with the full text of this article at NEJM.org, was reviewed and approved by an independent protocol review committee and by the institutional review board at each participating clinical site. An independent data and safety monitoring board oversaw the conduct of the trial and reviewed the safety and efficacy data. Data management and statistical analyses were performed at the data coordinating center (Axio Research, Seattle) with oversight by the executive committee for the trial (see the Supplementary Appendix, available at NEJM.org). After termination of the blinded study treatment on May 25, 2011, the members of the executive committee had full access to trial information and vouch for the accuracy and completeness of the data and analyses.
Patients were recruited at 92 clinical centers in the United States and Canada. After providing written informed consent, eligible patients entered a 4-to-8-week open-label phase during which they received simvastatin at a dose of 40 mg per day, plus niacin at doses that were increased weekly from 500 mg per day to 2000 mg per day. Patients in whom a dose of at least 1500 mg of niacin per day was associated with an acceptable side-effect profile were randomly assigned, in a 1:1 ratio, to niacin or matching placebo. Randomization was performed with the use of a secure Internet application. Patients attended clinic visits at 6-month intervals and were contacted by telephone in alternate quarterly intervals.