1. AIM HIGH Niacin plus Statin to prevent vascular events

2. 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:

3. 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 mmol/L ( 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:

4. 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:

5. Key outcomes Endpoint Niacin (%) Placebo (%)
Hazard ratio (95% CI) with niacin
p-value
Primary*
16.4
16.2
1.02 ( )
0.80
CHD death/nonfatal MI/ischaemic stroke/high risk ACS
10.0
9.3
1.08 ( )
0.49
CHD death/nonfatal stroke/ischaemic stroke
8.1
9.1
1.13 ( )
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:

6. 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:

7. 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:

8. 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: