NIACIN














  • All values are presented as change from baseline
  • Women tend to have a greater response to niacin than men
  • Reference [1]
Niaspan dose (mg at bedtime) Triglycerides HDL LDL Total
500 mg -5% +10% -3% -2%
1000 mg -11% +15% -9% -5%
1500 -28% +22% -14% -11%
2000 -35% +26% -17% -12%



AIM-HIGH Study - Niaspan vs Placebo for Secondary Prevention of CVD, NEJM (2011) [PubMed abstract]
  • The AIM-HIGH study enrolled 3414 patients with a history of CVD
Main inclusion criteria
  • Age ≥ 45 years
  • Documented CVD
  • HDL ≤ 42 mg/dl for men, ≤ 53 mg/dl for women
  • Triglycerides 100 - 400 mg/dl
  • LDL ≤ 180 mg/dl
Main exclusion criteria
  • Acute coronary syndrome within 4 weeks
  • CABG within 1 years
  • Stroke within 8 weeks
  • HgA1C > 9%
  • EF < 30%
  • AST or ALT > 2 X ULN
  • Recent acute gout
  • Serum creatinine ≥ 2.5 mg/dl
Baseline characteristics
  • Average age 64 years
  • History of myocardial infarction - 56%
  • History of stroke or cerebrovascular disease - 21%
  • History of peripheral vascular disease - 14%
  • Diabetes - 34%
  • Taking statin - 93%
  • Average LDL - 76 mg/dl
  • Average HDL - 35 mg/dl
  • Median triglyceride level - 163 mg/dl
Randomized treatment groups
  • Group 1 (1696 patients) - Placebo + Simvastatin
  • Group 2 (1718 patients) - Niaspan® 1500 - 2000 mg a day + Simvastatin
  • Simvastatin was dosed to achieve an LDL level between 40 - 80 mg/dl
  • Ezetimibe (Zetia®) could be added to both groups if needed to keep LDL ≤ 80 mg/dl
  • Nonstudy lipid-lowering drugs were not allowed
Primary outcome: Composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization
Results

Duration: The trial was stopped early after an average follow-up of 3 years due to a lack of efficacy
Outcome Placebo Niaspan Comparisons
Primary outcome 16.2% 16.4% HR 1.02, 95%CI [0.87 - 1.21], p=0.80
Nonfatal myocardial infarction 5.5% 6.1% HR 1.11, 95%CI [0.84 - 1.47], p=0.46
Ischemic stroke 1.1% 1.7% HR 1.61, 95%CI [0.89 - 2.90], p=0.11
Overall mortality 4.8% 5.6% HR 1.16, 95%CI [0.87 - 1.56], p=0.32
Average LDL at 3 years 68 mg/dl 65 mg/dl N/A
Average HDL at 3 years 39 mg/dl 44 mg/dl N/A
Median triglycerides at 3 years 152 mg/dl 120 mg/dl N/A
Flushing/itching causing discontinuation 2.5% 6.1% N/A
Drug discontinuation 20.1% 25.4% p<0.001

Findings: Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter (1.81 mmol per liter), there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels
HPS2-THRIVE Study - Niacin ER + Laropiprant vs Placebo for Secondary Prevention of CVD, NEJM (2014) [PubMed abstract]
  • The HPS2-THRIVE study enrolled 25,673 patients with a history of CVD
Main inclusion criteria
  • Age 50 - 80 years
  • History of CVD or diabetes with evidence of symptomatic CAD
Main exclusion criteria
  • Acute coronary syndrome or stroke within 3 months
  • Planned revascularization
  • ALT > 1.5 X ULN
  • Serum creatinine > 2.3 mg/dl
  • CK > 3 X ULN
Baseline characteristics
  • Average age 65 years
  • History of myocardial infarction - 68%
  • History of cerebrovascular disease - 32%
  • History of peripheral artery disease - 13%
  • Diabetes - 32%
  • Average LDL - 63 mg/dl
  • Average HDL - 44 mg/dl
Randomized treatment groups
  • Group 1 (12,838 patients) - Niacin extended-release 2000 mg + laropiprant 40 mg a day
  • Group 2 (12,835 patients) - Placebo
  • All patients received simvastatin 40 mg ± ezetimibe to keep total cholesterol < 135 mg/dl
  • All patients went through a run-in phase where tolerance to study medications was proven
  • Laropiprant is an antagonist of the prostaglandin D2 receptor DP1 that has been shown to improve adherence to niacin therapy by reducing flushing in up to two thirds of patients
Primary outcome: First major vascular event defined as major coronary event (nonfatal myocardial infarction or death from coronary causes), stroke of any kind, or coronary or noncoronary revascularization
Results

Duration: Median of 3.9 years
Outcome Niacin Placebo Comparisons
Primary outcome 13.2% 13.7% RR 0.96, 95%CI [0.90 - 1.03], p=0.29
Major coronary event 5.2% 5.4% RR 0.96, 95%CI [0.87 - 1.07], p=0.51
Any stroke 3.9% 3.9% RR 1.0, 95%CI [0.88 - 1.13], p=0.56
Any revascularization 6.3% 7.0% RR 0.90, 95%CI [0.82 - 0.99], p=0.03
Overall mortality 6.2% 5.7% RR 1.09, 95%CI [0.99 - 1.21], p=0.08
New-onset diabetes 5.7% 4.3% RR 1.32, 95%CI [1.16 - 1.51], p<0.001
GI side effect 3.1% 2.2% RR 1.39, 95%CI [1.20 - 1.62]
Myopathy 0.6% 0.1% RR 3.54, 95%CI [2.36 - 5.33]
Any serious bleeding event 2.5% 1.9% RR 1.38, 95%CI [1.17 - 1.62], p=0.0002
Drug discontinuation 25.4% 16.6% p<0.001
  • In the Niacin group, LDL decreased by 10 mg/dl on average and triglycerides decreased by 33 mg/dl while HDL increased by 6 mg/dl [14]

Findings: Among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events