AIM-HIGH Hypothesis:

• The hypothesis of AIM-HIGH is that combination anti-dyslipidemic therapy (extended-release niacin plus simvastatin) will be superior to statin monotherapy (simvastatin) when used as secondary prevention in reducing long-term clinical events in patients with documented vascular disease and atherogenic dyslipidemia. Based on these selection criteria, the vast majority of these patients are anticipated to satisfy current NCEP ATP III criteria for a diagnosis of metabolic syndrome.
  
  
• To date, there have been several large randomized controlled trials involving statin monotherapy versus placebo to reduce elevated LDL-C and clinical events in CHD patients, but only one secondary prevention randomized controlled trial to assess the role of raising low levels of HDL-C and/or lowering TG levels and its impact on favorably reducing CHD death, MI and stroke (VA-HIT). VA-HIT clearly demonstrated the superiority of gemfibrozil versus placebo in male veterans with CHD and low levels of HDL-C, but was limited in its overall generalizability because women were excluded. In addition, the increase in HDL-C in that study was quite modest (~6%) compared to what is anticipated with niacin.
  
  
• Thus, while VA-HIT provides important “proof of concept” that the “HDL hypothesis” of therapeutically raising low levels of HDL-C reduces coronary and cerebrovascular events during long-term follow-up, there has been, to date, no randomized controlled trial that has evaluated prospectively the role of “combination dyslipidemic therapy” in a more geographically and demographically-diverse population of men and women with vascular disease manifested as CHD, CVD or PAD and who have the increasingly common lipid profile of low HDL-C, elevated triglycerides (with or without elevated LDL-C), and features of insulin resistance (metabolic syndrome). The current gaps in our scientific knowledge and contemporary therapeutics as to how such patients should be managed optimally are large, and the proposed AIM-HIGH trial seeks to address these important considerations.

AIM-HIGH Overview:

• About 3,300 patients (1,650 in each group) will be randomized to receive simvastatin monotherapy or simvastatin plus niacin extended-release plus simvastatin. (A small number of participants (3-5%) may need to have ezetimibe (Zetia®), a prescription medication that also lowers blood cholesterol, added to their assigned study treatment to keep their cholesterol levels in the optimal range.)

  The estimated study duration used for sample size calculations comprises a planned two-year enrollment and a mean four years of follow-up. In any case, all randomized patients will be followed until study end date, with a minimum follow-up duration of three years and a maximal follow-up duration that corresponds to the time between the first randomization and the study end date (5 years).

The AIM-HIGH trial medications will be supplied by Abbot Laboratories, Abbott Park, IL:

• Simvastatin: 10mg, 20 mg, 40 mg and 80 mg tablets
• Extended-release niacin: 500mg and 1000mg tablets and matching placebos containing 50mg immediate-release niacin
• Ezetimibe 10 mg

The maximum doses permitted in this trial are:

• Extended-release niacin 2000 mg
• Simvastatin 80 mg
• Ezetimibe 10 mg

Click here for the complete AIM-HIGH protocol. (PDF size 396 KB)

• AIM-HIGH enables patients to receive expert lipid care and receive access to FDA-approved therapies. Coronary heart disease remains the leading cause of death and disability in the Western world, with approximately 12.6 million individuals in the United States having a history of myocardial infarction (MI), angina, or both.
• There is mounting evidence that standard therapies aimed at traditional risk factors have not optimized clinical outcomes.
• AIM-HIGH is the first large study to measure the independent effect of treating HDL-C and triglycerides with a combination of extended-release niacin (prescription Niaspan®) and simvastatin as compared to treatment with simvastatin alone in the prevention of heart disease.

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