AIM-HIGH: Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes

Trial Overview:

• AIM-HIGH is a multicenter, randomized, double-blind, parallel-group, controlled clinical trial designed to evaluate the treatment strategy of increasing low levels of HDL-cholesterol (HDL-C) and lowering elevated levels of triglycerides, in addition to lowering LDL cholesterol (LDL-C) in order to reduce the risk of heart attack, stroke and acute coronary syndrome.
  
  
• AIM-HIGH is designed to test whether the drug combination of extended-release niacin plus simvastatin is superior to simvastatin alone, at comparable levels of on-treatment LDL-C, for delaying the time to a first major cardiovascular (CV) disease outcome over a four-year median follow-up in patients with atherogenic dyslipidemia. Prior clinical trials have found only 25 to 35% CV risk reduction using statin monotherapy (i.e., event rate 2/3 to 3/4 of placebo rate). The study is needed to confirm whether statin-niacin combination therapy, designed to target a wider spectrum of dyslipidemic factors in addition to LDL-C, will provide a more substantial reduction (greater than 50%) of CV events.

Participant details:

• The study will enroll an estimated 3,300 men and women at least 45 years old at high risk of recurrent CV events by virtue of having established cardivascular disease together with the two dyslipidemic elements of metabolic syndrome: low HDL-C (≤ 40 mg/dl in men and 50mg/dl in women) and high triglycerides (TG) (≥ 150 mg/dl) in patients not on statin therapy. The study specifically aims to test this hypothesis for the primary composite clinical end point of CHD death, nonfatal MI, ischemic stroke, or hospitalization for high-risk acute coronary syndrome with objective evidence of ischemia (troponin-positive or ST-segment deviation). A secondary end point is the composite of CHD death, nonfatal MI, or ischemic stroke.
  
• AIM-HIGH provides participants with expert lipid care and access to FDA-approved therapies that may protect against coronary heart disease – the leading cause of death and disability in the Western world. Approximately 12.6 million individuals in the United States have a history of myocardial infarction (MI), angina, or both.
  
• Enrollment of patients at clinical sites in the U.S. and Canada began in the Fall of 2005. Follow-up will last for an average of four years.

Trial Impact:

• The study will be 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.
  
  
• Coronary heart disease (CHD) 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.
  
  
• Epidemiologic studies confirm the high prevalence of atherogenic dyslipidemia and its impact on CV event rates. Preliminary clinical trials suggest that targeting these factors with dyslipidemic therapy will reduce CV events.
  
  
• There is mounting evidence that standard therapies aimed at traditional risk factors have not optimized clinical outcomes. Even among patients entering the Heart Protection Study with baseline LDL-C already near or at goal and who achieved a mean on-trial LDL-C of 70 mg/dL with simvastatin, the five-year risk of an event was still 18% (projecting to a ten-year risk of 36%). This residual and unacceptably high risk is likely due to the increasing prevalence of obesity, type II diabetes mellitus, and the metabolic syndrome.
  
  
• Conventional LDL-C-focused therapies are not effective in targeting this type of dyslipidemia. Evidence that therapy directed at atherogenic dyslipidemia among patients with CHD can lower outcomes was shown with gemfibrozil in the VA-HIT trial, which showed a 22 to 24% cardiovascular (CV) event reduction by raising HDL-C (by an average of six percent) and lowering triglycerides (by an average of 31%). Niacin is an even more effective agent for simultaneously raising HDL-C and lowering triglycerides and levels of small dense LDL, and holds the most promise among existing therapies for substantial risk reduction in this population when added to a statin. This was demonstrated in the HDL Atherosclerosis Treatment Study (HATS) trial in which atherosclerosis progression was virtually halted and CV events were reduced by 60 to 90% using combined niacin plus statin therapy.

Sponsorship Information:

• This trial is sponsored by the National Heart, Lung, and Blood Institute (NIH, www.nhlbi.nih.gov) with supplemental funding from Abbott Laboratories (www.abbott.com).