AIM-HIGH TRIAL - CardiologyTrials.org

AIM-HIGH TRIAL
Problem	Cardiovascular disease
Format	Double-blinded multi-center RCT
Treatment	Niacin
Control	Placebo
Population	3414 patients
Inclusion criteria	See http://www.nejm.org/doi/suppl/10.1056/NEJMoa1107579/suppl_file/nejmoa1107579_appendix.pdf 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 enrollment 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 Page 4 of 18 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 1 : 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 http://www.nejm.org/doi/suppl/10.1056/NEJMoa1107579/suppl_file/nejmoa1107579_appendix.pdf 1. Hospitalization for acute coronary syndrome and discharge within 4 weeks prior to planned enrollment 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 follow-up 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 therapy 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, amiodarone • 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 contraception 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)