Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy

The AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-2267.

Background 

Residual cardiovascular (CV) risk persists among high-risk patients despite achievement of target LDL-C levels. In addition to elevated LDL-C, low HDL-C has been found in epidemiological studies to independently predict coronary heart disease (CHD) risk. 

In a post-hoc analysis of the Treating to New Targets (TNT) trial, the 5-year rate of CV events was 25% lower among participants in the highest quintile of HDL-C levels. This suggests that HDL-C levels have prognostic value for patients receiving statin therapy independent of LDL-C levels. 

The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) study assessed whether adding extended-release (ER) niacin to intensive statin therapy reduces CV event risk among patients with established atherosclerotic cardiovascular disease (ASCVD) and atherogenic dyslipidemia. (Click here for slide) 

Design  

AIM-HIGH enrolled 3,414 patients with ASCVD and atherogenic dyslipidemia. All patients had low baseline HDL-C (<40 mg/dL men, <50 mg/dL women), elevated triglycerides (TG; 150-400 mg/dL), and LDL-C <180 mg/dL. Patients were randomized to ER niacin 1,500-2,000 mg/day or matching placebo. All patients received simvastatin 40-80 mg/day plus ezetimibe 10 mg/day (if needed) to maintain LDL-C 40-80 mg/dL. 

The primary endpoint was first event of the composite of CHD death, nonfatal myocardial infarction (MI), ischemic stroke, hospitalization for acute coronary syndrome (ACS), or symptom-driven coronary or cerebral revascularization. 

AIM-HIGH was stopped prematurely after a mean of 3 years due to lack of efficacy in the niacin group. (Click here for slide) 

Select baseline characteristics from the AIM-HIGH study population are shown below: (Click here for slide) 

 
ER niacin + statin  
(N=1,718) 
Placebo + statin 
(N=1,696) 
Median age, yr  63.7 63.7
Male gender 1,465 (85.3%) 1,445 (85.2%)
Presenting history/diagnosis    
   MI 968 (56.3%) 955 (56.3%)
   PCI 1,057 (61.5%) 1,044 (61.6%)
   Stroke, cerebrovascular disease 358 (20.8%) 362 (21.3%)
   Peripheral vascular disease 234 (13.6%) 231 (13.6%)
   Diabetes 588 (34.2%) 570 (33.6%)
Statin use at baseline 1,595 (92.8%) 1,601 (94.4%)
Prior use of niacin 324 (18.9%) 338 (19.9%)  

Results  

Among subjects taking a statin at entry (n=3,196), baseline LDL-C was 71 mg/dL; HDL-C 35 mg/dL; TG 161 mg/dL. Among subjects not taking a statin at baseline, baseline LDL-C was 124 mg/dL; HDL-C 33 mg/dL; TG 215 mg/dL.

At 2 years: (Click here for slide) 

  • LDL-C was 62 mg/dL among subjects in the statin + niacin group and 68 mg/dL in the statin + placebo group
  • HDL-C was 42 mg/dL in the statin + niacin group and 38 mg/dL in the satin + placebo group (P<0.001)
  • TG was 122 mg/dL in the statin + niacin group and 153 mg/dL in the satin + placebo group

The primary endpoint occurred in 16.2% of subjects in the placebo + statin group and 16.4% in the niacin + statin group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.87-1.21; P=0.80). (Click here for slide) 

The composite secondary endpoint of CHD mortality, nonfatal MI, high-risk ACS, or ischemic stroke occurred in 9.3% of subjects in the placebo + statin group and 10.0% in the niacin + statin group (HR, 1.08; 95% CI, 0.87-1.34; P=0.49). The composite secondary endpoint of CHD mortality, nonfatal MI, or ischemic stroke occurred among 8.1% of subjects in the placebo + statin group and 9.1% in the niacin + statin group (HR, 1.13; 95% CI, 0.90-1.42; P=0.30.) (Click here for slide) 

Related content: 

Overview: HPS2-THRIVE randomized placebo-controlled trial in 25,673 high-risk patients of ER niacin/laropiprant  

Slide: HPS2-THRIVE: Niacin and Vascular Risk  

Slide: HPS2-THRIVE: Niacin and Laropiprant for Vascular Risk Reduction  

Slide: HPS2-THRIVE: Baseline Characteristics  

Slide: HPS2-THRIVE: LDL-Lowering Therapy Compliance  

Slide: HPS2-THRIVE: Safety & Tolerability of Niacin ER + Laropiprant  

Slide: HPS2-THRIVE: Liver & Muscle-Related Adverse Events   

 

 

March 2013 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

Last Modified: 3/23/2015