Before the statin era, the Coronary Drug Project RCT (8341 patients) showed that niacin monotherapy in patients with definite electrocardiographic evidence of previous myocardial infarction (MI) reduced nonfatal MI to 8.9% compared with 12.2% for placebo (P=.002).1 (See TABLE.1-4) It also decreased long-term mortality by 11% compared with placebo (P=.0004).5
Adverse effects such as flushing, hyperglycemia, gastrointestinal disturbance, and elevated liver enzymes interfered with adherence to niacin treatment (66.3% of patients were adherent to treatment with niacin vs 77.8% for placebo). The study was limited by the fact that flushing essentially unblinded participants and physicians.
But adding niacin to a statin has no effect
A 2014 meta-analysis driven by the power of the large HPS2-Thrive study evaluated data from 35,301 patients primarily in secondary prevention trials.2,3 It found that adding niacin to statins had no effect on all-cause mortality, coronary heart disease mortality, nonfatal MI, or stroke. The subset of 6 trials (N=4991) assessing niacin monotherapy did show a reduction in cardiovascular events (odds ratio [OR]=0.62; confidence interval [CI], 0.54-0.82), whereas the 5 studies (30,310 patients) involving niacin with a statin demonstrated no effect (OR=0.94; CI, 0.83-1.06).
No benefit from niacin/statin therapy despite an improved lipid profile
A 2011 RCT included 3414 patients with coronary heart disease on simvastatin who were randomized to niacin or placebo.4 All patients received simvastatin 40 to 80 mg ± ezetimibe 10 mg/d to achieve low-density lipoprotein (LDL) cholesterol levels of 40 to 80 mg/dL.
At 3 years, no benefit was seen in the composite CVD primary endpoint (hazard ratio=1.02; 95% CI, 0.87-1.21; P=.79) even though the niacin group had significantly increased median high-density lipoprotein (HDL) cholesterol compared with placebo and lower triglycerides and LDL cholesterol compared with baseline.
A nonsignificant trend toward increased stroke in the niacin group compared with placebo led to early termination of the study. However, multivariate analysis showed independent associations between ischemic stroke risk and age older than 65 years, history of stroke/transient ischemic attack/carotid artery disease, and elevated baseline cholesterol.6
Niacin combined with a statin increases the risk of adverse events
The largest RCT in the 2014 meta-analysis (HPS2-Thrive) evaluated 25,673 patients with established CVD receiving cholesterol-lowering therapy with simvastatin ± ezetimibe who were randomized to niacin or placebo for a median follow-up period of 3.9 years.3 A pre-randomization run-in phase established effective cholesterol-lowering therapy with simvastatin ± ezetimibe.