AIM-HIGH Trial
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Click here to download slides for 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
| Timeline | |
| Start Date | September 2005 |
| End Date | September 2012 |
| Status | Terminated |
The previous information was derived from ClinicalTrials.gov on 10/06/2013 using the identification number NCT00120289.
Study Description
| Study Description | |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | |
| Allocation | Randomized |
| Endpoint | Efficacy Study |
| Interventional Model | Parallel Assignment |
| Masking | Double Blind |
| Study Details | |
| Primary Purpose | Prevention |
| Condition | Cardiovascular Diseases Heart Diseases Cerebrovascular Accident Coronary Disease Atherosclerosis Myocardial Infarction |
| Intervention | Drug: Extended release niacin (2,000 mg/day or 1,500 mg/day if higher dose not tolerated) Drug: Simvastatin (Dose adjusted to achieve LDL-C 40 mg/dL - 80 mg/dL, adding ezetimibe (10 mg/day) if needed to achieve LDL-C target) |
| Study Arms | Experimental: Extended release niacin plus simvastatin Active Comparator: Simvastatin alone |
| Population Size | 3414 |
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)
- 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)
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)
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 [ Time Frame: Time to first event ] [ Designated as safety issue: Yes ]
Secondary Outcomes
- Composite endpoint of CHD death, non-fatal MI, high-risk ACS or ischemic stroke [ Time Frame: Time to first event ] [ Designated as safety issue: Yes ]
- Composite endpoint of CHD death, non-fatal MI, or ischemic stroke [ Time Frame: Time to first event ] [ Designated as safety issue: Yes ]
- Cardiovascular mortality [ Time Frame: Time to event ] [ Designated as safety issue: Yes ]
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.[1][2][3][4][5][6]
References
- ↑ Boden WE, Probstfield JL, Anderson T; et al. (2011). "Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy". N. Engl. J. Med. 365 (24): 2255–67. doi:10.1056/NEJMoa1107579. PMID 22085343. Unknown parameter
|month=ignored (help) - ↑ Michos ED, Sibley CT, Baer JT, Blaha MJ, Blumenthal RS (2012). "Niacin and statin combination therapy for atherosclerosis regression and prevention of cardiovascular disease events: reconciling the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial with previous surrogate endpoint trials". J. Am. Coll. Cardiol. 59 (23): 2058–64. doi:10.1016/j.jacc.2012.01.045. PMID 22520249. Unknown parameter
|month=ignored (help) - ↑ Brinton EA (2012). "Search and rescue for hypotheses surviving AIM-HIGH, the niacin therapy earthquake: still problematic after the primary publication". J Clin Lipidol. 6 (4): 312–7. doi:10.1016/j.jacl.2012.03.005. PMID 22836067.
- ↑ Nicholls SJ (2012). "The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial: to believe or not to believe?". J. Am. Coll. Cardiol. 59 (23): 2065–7. doi:10.1016/j.jacc.2012.02.021. PMID 22520248. Unknown parameter
|month=ignored (help) - ↑ Nicholls SJ (2012). "Is niacin ineffective? Or did AIM-HIGH miss its target?". Cleve Clin J Med. 79 (1): 38–43. doi:10.3949/ccjm.79a.11166. PMID 22219232. Unknown parameter
|month=ignored (help) - ↑ Sharma M (2011). "Combination therapy for dyslipidemia". Curr. Opin. Cardiol. 26 (5): 420–3. doi:10.1097/HCO.0b013e3283499ef1. PMID 21832894. Unknown parameter
|month=ignored (help)