Donald A. Smith, MD, MPH
Does adding extended-release (ER) niacin to simvastatin reduce cardiovascular (CV) events in patients with atherosclerotic CV disease and atherogenic dyslipidemia?
Randomized placebo-controlled trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes [AIM-HIGH] trial). ClinicalTrials.gov NCT00120289.
Blinded* (patients, study personnel, clinical endpoints committee).
Mean 3 years (trial was stopped early for lack of efficacy when prespecified stopping rules were met).
92 clinical centers in the USA and Canada.
3414 patients ≥ 45 years of age (mean age 64 y, 85% men) who had ischemic CV disease (stable coronary heart disease [CHD], cerebrovascular or carotid disease, or peripheral arterial disease); an acceptable side effect profile using niacin, ≥ 1500 mg/d, and simvastatin, 40 mg/d, during the 4- to 8-week run-in period; and high-density lipoprotein cholesterol (HDL-C) levels < 1.03 mmol/L (< 40 mg/dL) in men or < 1.29 mmol/L (< 50 mg/dL) in women, triglyceride levels 1.69 to 4.52 mmol/L (150 to 400 mg/dL), and low-density lipoprotein cholesterol (LDL-C) levels < 4.65 mmol/L (< 180 mg/dL) in patients not taking a statin at enrollment. Exclusion criteria included having planned revascularization or hospitalization for an acute coronary syndrome (ACS) in the past 4 weeks, or stroke in the past 8 weeks.
ER niacin, 1500 to 2000 mg/d (n = 1718), or matching placebo containing immediate-release (IR) niacin, 50 mg per tablet (n = 1696). Both groups used simvastatin, 40 to 80 mg/d, with or without ezetimibe, 10 mg/d, targeted to an LDL-C level of 1.03 to 2.07 mmol/L (40 to 80 mg/dL).
Primary composite endpoint was the first of CHD death, nonfatal myocardial infarction (MI), ischemic stroke, symptom-driven coronary or cerebral revascularization, or hospitalization for an ACS. Other endpoints included CV death. 800 events over 4.6 years were needed to detect a 25% reduction in the primary endpoint (85% power, 1-sided α = 0.025).
98% (intention-to-treat analysis).
The main results are in the Table.
Adding extended-release niacin to simvastatin did not improve cardiovascular outcomes in patients with cardiovascular disease and atherogenic dyslipidemia.
Extended-release niacin vs placebo in patients with CV disease and atherogenic dyslipidemia receiving simvastatin†
†CV = cardiovascular; other abbreviations defined in Glossary. RRI and CI calculated from hazard ratios and control event rates in article.
‡First event of coronary heart disease death (1.2% vs 1.5%), nonfatal myocardial infarction (5.4% vs 4.7%), ischemic stroke (1.6% vs 0.9%), symptom-driven coronary or cerebral revascularization (4.7% vs 5.1%), or hospitalization for an acute coronary syndrome (3.7% vs 4.0%).
Smith DA. Adding niacin to simvastatin did not improve clinical outcomes in patients with CV disease and dyslipidemia. Ann Intern Med. ;156:JC4–8. doi: 10.7326/0003-4819-156-8-201204170-02008
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Published: Ann Intern Med. 2012;156(8):JC4-8.
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