AIM-HIGH Niacin Plus Statin to Prevent Vascular Events

Préparation ESC Septembre 20/09/2018 NY-160626.038/020131YlsjoLS1 AIM-HIGH: Rationale Conventional LDL-C lowering with statins fails to substantially address the high residual cardiovascular risk due to non-LDL lipids Does adding niacin, which raises HDL cholesterol (in addition to lowering LDL-C and triglycerides) provide additional clinical benefit? There is mounting evidence that "conventional" therapies aimed at traditional risk factors have not optimized clinical outcomes. In the Heart Protection Study (1), patients with baseline LDL-C at or near goal (LDL-C < 116 mg/dL) who achieved a mean on-trial LDL-C of 70 mg/dL with simvastatin, still had a 5-year risk of a major vascular event of 18% (projecting to a 10-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. These disorders are typically accompanied by a constellation of abnormalities that include impaired glycemic control, hypertension, procoagulant and inflammatory states, and atherogenic dyslipidemia. The latter includes a wide spectrum of lipid abnormalities (low HDL-C, high triglycerides and triglyceride-rich remnant lipoproteins, and a preponderance of small dense, highly-oxidizable LDL particles). 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 6%) and lowering triglycerides (by an average of 31%) (2). AIM-HIGH aims to evaluate whether statin-niacin combination therapy, designed to target a wider spectrum of dyslipidemic factors in addition to LDL-C, will substantailly reduce this residual CV risk. References 1. Heart Protection Study Collaborative Group. Lancet 2002;360:7-22. 2. Rubins HB et al. N Engl J Med 1999;341:410-8

AIM-HIGH: Study design Préparation ESC Septembre 20/09/2018 AIM-HIGH: Study design NY-160626.038/020131YlsjoLS1 Randomised, placebo-controlled, double-blind trial in 3,300 high- risk patients aged at least 45 years and with established vascular disease AND Atherogenic dyslipidaemia: LDL-C <4.1 mmol/L (160 mg/dL) HDL-C <1.0 mmol/L (40 mg/dL) in men and <1.3 mmol/L (50 mg/dL) in women Triglycerides 1.7-4.5 mmol/L (150-400 mg/dL) Patients randomized to ER niacin (2 g) vs.placebo on top of optimal statin therapy Primary Outcome: Composite end point of CHD death, nonfatal MI, ischemic stroke, or hospitalization for acute coronary syndrome (measured at time to first occurrence of one of these events) www.ClinicalTrials.gov NCT00120289