AIM-HIGH Trial

# Official Title
AIM HIGH: Niacin Plus Statin to Prevent Vascular Events

# Objective
The purpose of this study is to determine whether raising "good cholesterol" with a drug based on the vitamin niacin, while lowering "bad cholesterol" with a statin drug, can prevent more heart disease than the statin alone.

# Sponsor
Axio Research. LLC

# Timeline
The previous information was derived from ClinicalTrials.gov on 10/06/2013 using the identification number NCT00120289.

# Study Description
The previous information was derived from ClinicalTrials.gov on 10/06/2013 using the identification number NCT00120289.

# Eligibility Criteria

## Inclusion Criteria
Men and women aged 45 and older with established vascular disease and atherogenic dyslipidemia
- Established vascular disease defined as one or more of the following:
Documented coronary artery disease (CAD)
Documented cerebrovascular or carotid disease
Documented symptomatic peripheral arterial disease (PAD)
- Documented coronary artery disease (CAD)
- Documented cerebrovascular or carotid disease
- Documented symptomatic peripheral arterial disease (PAD)
- Atherogenic dyslipidemia defined as:
LDL-C of less than or equal to 160 mg/dL (4.1 mmol/L)
HDL-C of less than or equal to 40 mg/dL (1.0 mmol/L) for men or less than or equal to 50 mg/dL (1.3 mmol/L) for women
TG greater than or equal to 150 mg/dL (1.7 mmol/L) and less than or equal to 400 mg/dL (4.5 mmol/L)
- LDL-C of less than or equal to 160 mg/dL (4.1 mmol/L)
- HDL-C of less than or equal to 40 mg/dL (1.0 mmol/L) for men or less than or equal to 50 mg/dL (1.3 mmol/L) for women
- TG greater than or equal to 150 mg/dL (1.7 mmol/L) and less than or equal to 400 mg/dL (4.5 mmol/L)
For patients entering the trial on a statin
- The upper limit for LDL-C is adjusted according to the specific statin and statin dose
HDL-C of less than or equal to 42 mg/dL (1.1 mmol/L) for men or less than or equal to 53 mg/dL (1.4 mmol/L) for women
TG greater than or equal to 125 mg/dL (1.4 mmol/L) and less than or equal to 400 mg/DL (4.5 mmol/L)
- The upper limit for LDL-C is adjusted according to the specific statin and statin dose
- HDL-C of less than or equal to 42 mg/dL (1.1 mmol/L) for men or less than or equal to 53 mg/dL (1.4 mmol/L) for women
- TG greater than or equal to 125 mg/dL (1.4 mmol/L) and less than or equal to 400 mg/DL (4.5 mmol/L)

## Exclusion Criteria
- Coronary artery bypass graft (CABG) surgery within 1 year of planned enrollment (run-in phase)
- Percutaneous coronary intervention (PCI) within 4 weeks of planned enrollment (run-in phase)
- Hospitalization for acute coronary syndrome and discharge within 4 weeks of planned enrollment (run-in phase)
- Fasting glucose greater than 180 mg/dL (10 mmol/L) or hemoglobin A1C greater than 9%
- For patients with diabetes, inability or refusal to use a glucometer for home monitoring of blood glucose
- Concomitant use of drugs with a high probability of increasing the risk for hepatotoxicity or myopathy, such as those predominantly metabolized by cytochrome  :P450 system 3A4, including but not limited to cyclosporine, gemfibrozil, fenofibrate, itraconazole, ketoconazole, HIV protease inhibitors, nefazodone, :verapamil, amiodarone; lipid-lowering drugs (other than the investigational drugs) such as statins, bile-acid sequestrants, cholesterol absorption inhibitors :(e.g., ezetimibe), fibrates or high-dose, antioxidant vitamins (vitamins C, E, or beta carotene) that can interfere with the HDL-raising effect of niacin

# Outcomes

## Primary Outcomes
Composite end point of CHD death, nonfatal MI, ischemic stroke, hospitalization for non-ST segment elevation acute coronary syndrome (ACS), or symptom-driven coronary or cerebral revascularization  

## Secondary Outcomes
- Composite endpoint of CHD death, non-fatal MI, high-risk ACS or ischemic stroke  
- Composite endpoint of CHD death, non-fatal MI, or ischemic stroke  
- Cardiovascular mortality  

# Publications

## Results
The trial was stopped prematurely for futility after a follow-up of 36 months.  At two years compared to placebo, niacin increased HDL-C levels and reduced triglyceride and LDL-C levels but there was no reduction in the rate of primary endpoint or all-cause mortality with niacin. Moreover, there was a trend towards more ischemic strokes in the niacin group. This led to the decision to halt the trial prematurely.

## Conclusion
In patients with established atherosclerotic cardiovascular disease with LDL cholesterol below 70mg/dl, no incremental clinical benefit was observed from addition of niacin to simvastatin during a 36 month follow-up. Also, elevations in HDL-C levels in the placebo group were higher than expected which may have reduced the competency of the trial to detect a real benefit with niacin therapy.