Authors
AIM-HIGH investigators
Title
Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy
References
N Engl J Med 2011; 365:2255-2267
Background
In patients with established cardiovascular disease, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein (LDL) cholesterol levels with statin therapy. It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein (HDL) cholesterol is superior to simvastatin alone in reducing such residual risk.
Purpose
To test whether extended-release niacin added to intensive statin therapy, as compared with statin therapy alone, would reduce the risk of cardiovascular events in patients with established atherosclerotic cardiovascular disease and atherogenic dyslipidemia (low levels of HDL cholesterol, elevated triglyceride levels, and small, dense particles of LDL cholesterol).
Design
  • Multicenter, randomized, double-blind trial
  • 3414 patients age >45 years with established CV disease (CAD, CVD, PAD)
  • Low HDL (<1.0mmol/L for men; <1.3mmol/L for women)
  • Triglycerides between 1.7-4.5mmol/L
  • LDL <4.7mmol/L
Exclusion Criteria
  • ACS or planned revascularization within 4 weeks of enrollment
  • Stroke within preceding 8 weeks
  • Fasting glucose >10mmol/L; HbA1c >9.0%
  • Creatinine >220umol/L
  • Concomitant treatment with another medication known to interact with statin/fibrate
  • LVEF <30%
  • Severe liver disease or ALT > 2x ULN
  • Severe uncontrolled HTN (>200/100mmHg)
Follow-Up
Mean 3 years
Treatment Regimen
  • 4-8 week open label phase: simvastatin 40mg/day plus niacin at doses that were increased weekly from 500mg/day to 2000mg/day.
  • Patients who tolerated at least 1500mg/day were randomized to niacin (1500-2000mg) or placebo
  • Follow-up visits at 6 monthly intervals
  • Dose of simvastatin adjusted to maintain LDL 1.0-2.1mmol/L
Results

Primary Endpoints

Placebo + statin
n=1696		ER-Niacin + statin
n=1718		Hazard Ratiop
Major CV event (cardiac death, non-fatal MI, or non-fatal stroke, hospitalization for ACS, or revascularization)
16.2%16.4%1.02 (0.87–1.21)0.80

Niacin therapy (at 2 years) had significantly increased the median HDL cholesterol level from 0.9mmol/L to 1.1 mmol/L, lowered the triglyceride level from 1.9mmol/L to 1.4mmol/L, and lowered the LDL cholesterol level from 1.9mmol/L) to 1.6mmol/L

Secondary Outcomes

(see study for complete list)

Placebo + statin
n=1696		ER-Niacin + statin
n=1718		Hazard Ratiop
Cardiac death
2.2%2.6%1.17 (0.76–1.80)0.47
Death from coronary heart disease, nonfatal myocardial infarction, or ischemic stroke
8.1%9.1%1.13 (0.90–1.42)0.30
Summary
Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less 1.8mmol/L, there was no incremental clinical benefit from the addition of niacin to statin therapy during the 36-month follow-up period despite significant improvements in HDL cholesterol and triglyceride levels.