AIM HIGH Niacin plus Statin to prevent vascular events

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? AIM-HIGH Investigators. N Engl J Med 2011;365:2255-67

Study Design Randomised, placebo-controlled, double-blind trial in 3,414 high- risk patients aged at least 45 years and with established vascular disease AND: Atherogenic dyslipidemia 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 (1.5-2 g) vs.placebo on top of optimal statin therapy. Primary outcome: Composite end point of CHD death, nonfatal MI, ischemic stroke, hospitalization for acute coronary syndrome or symptom-driven vascularisation AIM-HIGH Investigators. N Engl J Med 2011;365:2255-67

Statistical considerations This trial sought to determine whether extended release niacin reduces cardiovascular events in patients treated to low LDL-C levels with a statin. It was an event driven trial designed to have an 85% power to detect a 25% reduction in cardiovascular events. It was calculated that a sample size of 3400 participants followed for a mean of 4.6 years would generate the required 800 primary events. The study was terminated early for futility at which time there had been about 550 primary events. AIM-HIGH Investigators. N Engl J Med 2011;365:2255-67

Key outcomes Endpoint Niacin (%) Placebo (%) Hazard ratio (95% CI) with niacin p-value Primary* 16.4 16.2 1.02 (0.87-1.21) 0.80 CHD death/nonfatal MI/ischaemic stroke/high risk ACS 10.0 9.3 1.08 (0.87-1.34) 0.49 CHD death/nonfatal stroke/ischaemic stroke 8.1 9.1 1.13 (0.90-1.42) 0.30 *composite of coronary heart disease (CHD) death, nonfatal myocardial infarction (MI), ischaemic stroke, hospitalisation for acute coronary syndrome (ACS) or symptom-driven coronary or cerebral revascularisation AIM-HIGH Investigators. N Engl J Med 2011;365:2255-67

Change in lipids Median (% change from baseline) ER niacin + simvastatin Simvastatin Median Δ between groups, mg/dL LDL-Cholesterol 62 (-13.6%) 67 (-7.6%) -5 HDL-Cholesterol 42 (25%) 38 (11.8%) +4 Triglycerides 120 (-30.8%) 152 (-9.9%) -32 AIM-HIGH Investigators. N Engl J Med 2011;365:2255-67

Key Issues Treatment with niacin increased HDL-C levels by 25% to an on-treatment level of 42 mg/dL. However, the level of HDL-C also increased substantially in the placebo group to an on-treatment level of 38 mg/dL. As a consequence, the on-treatment difference in HDL-C between the two groups was only 4 mg/dL. This difference would predict at most 10% difference in CV events. AIM-HIGH Investigators. N Engl J Med 2011;365:2255-67

Conclusions Thus, AIM-HIGH HAS NOT tested the HDL hypothesis; nor was it powered sufficiently to test the potential benefits of niacin. AIM-HIGH Investigators. N Engl J Med 2011;365:2255-67