Problem Cardiovascular disease
Format Double-blinded multi-center RCT
Treatment Niacin
Control Placebo
Population 3414 patients
Inclusion criteria See

Established Vascular Disease satisfying at least one of the following:
a. Documented CHD with > one of the following:
i. Documented multi-vessel CHD, with one or more > 50% stenoses in > two major
epicardial coronary arteries by angiography. Patients with prior successful
percutaneous coronary intervention (PCI), even with no residual stenosis, were eligible.
ii. Documented prior MI satisfying > two of the following:
• Characteristic ischemic chest pain or pain in associated referral areas
• Elevation of CK (> twice the upper limit of normal) and/or CK-MB (> twice the upper
limit of normal) and/or troponin T or I (> twice the upper limit of normal)
• New Q waves in adjacent ECG leads, or new dominant R wave in V1
iii. Hospitalization for non-ST segment elevation acute coronary syndrome with objective
evidence of ischemia (ST-segment deviation or biomarker positivity), stable > 4 weeks
following hospital discharge.
b. Documented cerebrovascular or carotid disease with at least one of the following:
i. Documented ischemic stroke within the past 5 years but not < 8 weeks prior to
ii. Symptomatic carotid artery disease with ≥ 50% stenosis
iii. Asymptomatic carotid stenosis ≥ 70%
iv. History of carotid revascularization (surgical or catheter based) AIM-HIGH Appendix
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c. Documented PAD with > one of the following:
i. Ankle-brachial index < 0.85 with or without claudication
ii. History of aorto-iliac or peripheral arterial intervention (surgical or catheter based)
2. AND Atherogenic Dyslipidemia defined as:
a. If off statins at entry, all of the following:
i. LDL-C ≤ 180 mg/dL (4.7 mmol/L)
ii. HDL-C ≤ 40 mg/dL (1.0 mmol/L) for men or ≤ 50 mg/dL (1.3 mmol/L) for women
iii. Triglycerides 150 – 400 mg/dL (1.7 – 4.5 mmol/L)
b. If on a statin with or without ezetimibe at entry, the equivalent lipid criteria satisfied
i. Upper limit for LDL-C adjusted according to dose and published effect of particular statin
ii. HDL-C ≤ 42 mg/dL (1.1 mmol/L) for men or ≤ 53 mg/dL (1.4 mmol/L) for women
iii. Triglycerides 100 – 400 mg/dL (1.1 – 4.5 mmol/L)
Exclusion criteria See

1. Hospitalization for acute coronary syndrome and discharge within 4 weeks prior to planned
2. Coronary Artery Bypass Graft (CABG) surgery within 1 year of planned enrollment (run-in phase),
unless there has been a new, intercurrent acute coronary syndrome event or recurrent angina,
associated with angiographic evidence of disease progression (≥ 50% stenosis) in 1 or more native
vessels or bypass grafts, regardless of whether subsequently treated with PCI/stenting
3. Planned percutaneous coronary intervention (PCI) within 4 weeks prior to planned enrollment4. Stroke within 8 weeks prior to enrollment
5. Fasting glucose >180 mg/dL (10 mmol/L) or hemoglobin A1C >9.0%
6. Inability or refusal to use a glucometer for home glucose monitoring (diabetic patients)
7. CHD associated with unstable angina and symptoms refractory to maximal medical therapy
8. Post MI course complicated by persistent rest angina, shock or persistent congestive heart failure, or
if need for urgent revascularization is high
9. Patients with left main coronary disease ≥50% and no prior CABG
10. Ejection fraction <30%
11. Cardiogenic shock, pulmonary edema or CHF unresponsive to standard medical therapy
12. Concomitant valvular heart disease likely to require surgery or adversely affect prognosis during
13. Congenital or primary cardiomyopathy likely to adversely affect prognosis during follow-up
14. Resuscitated out-of-hospital sudden death or symptomatic sustained or non-sustained ventricular
tachycardia without an implantable cardioverter-defibrillator (ICD)
15. Significant systemic hypertension (blood pressure >200/100 mmHg) unresponsive to medical
16. Active peptic ulcer disease
17. AST or ALT > 2 times upper limit of normal or active liver disease
18. Recent history of acute gout. (For patients with baseline uric acid > 7.0 mg/dL [415 umol/L],
treatment with allopurinol is recommended but not mandated)
19. Chronic renal insufficiency with creatinine ≥ 2.5mg/dL (220 umol/L)
20. Patients who cannot discontinue the following excluded concomitant medications:
• 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: AIM-HIGH Appendix
cyclosporine, itraconazole, ketoconazole, HIV protease inhibitors, nefazodone, verapamil,
• Lipid-lowering drugs (other than the investigational drugs), such as statins, bile-acid sequestrants,
fish oils, cholesterol absorption inhibitors, fibrates
• High-dose, antioxidant vitamins (vitamins C, E, or beta-carotene)
21. Pregnant (or likely to become pregnant) women or pre-menopausal women not using adequate
22. Significant co-morbidity likely to cause death in the 3-5 year follow-up
23. Patients with AIDS/active HIV infection, due to potential confounding drug interactions
24. Significant active history of substance abuse within 5 years
25. Unwillingness/inability to give informed consent or follow study protocol
26. Current participation in another clinical study or trial that involves a study drug or intervention
27. Unwillingness of patient’s physician to allow participation in the study
Follow-up Mean 3 years
Primary endpoint First event of composite of death from CHD, nonfatal MI, ischemic stroke, hospitalization for ACS, or symptom-driven coronary or cerebral revasc.
Secondary endpoint(s) 1) composite of death from CHD, nonfatal MI, ischemic stroke, or hospitalization for a high-risk ACS; 2) death from CHD, nonfatal MI, or ischemic stroke
Details All patients received simvastatin, 40 to 80 mg per day, plus ezetimibe, 10 mg per day, if needed, to maintain an LDL cholesterol level of 40 to 80 mg per deciliter
Brief summary: Niacin added to statin +- ezetimibe improved HDL/TAG but did not improve outcomes
PAPER: Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy
Date 15 Nov 2011
Journal N Engl J Med. 2011 Nov 15. [Epub ahead of print]
Information N.B. All patients received simvastatin 40-80mg +- ezetimibe, 10mg per day

Significant improvements in HDL and triglycerides
No additional cardiovascular benefits
Non significant trend towards INCREASED stroke risk with niacin (p=0.11)