Table 2.
Cardiovascular outcomes trials of niacin and fibrates.
| Trial | Intervention | Patient Population | Primary Endpoint | Primary Endpoint Met? | HR/RR for Intervention |
|---|---|---|---|---|---|
| Trials of Niacin | |||||
| AIM-HIGH [41] | Extended-release niacin 1500–2000 mg/day plus simvastatin vs placebo plus simvastatin | 3414 adults aged ≥45 years receiving high-intensity statin therapy with established CV disease, HDL-C <40 mg/dL, and TG 150–400 mg/dL | CHD death, non-fatal MI, ischemic stroke, hospitalization >23 h for ACS, or symptom-driven coronary or cerebral revascularization | No | HR 1.02; 95% CI 0.87–1.21; P = 0.80 |
| HPS2-THRIVE [7] | Niacin ER 1 g/day in combination with laropiprant 20 mg for 4 weeks followed by ER niacin 2 g/day in combination with laropiprant 40 mg/day for 3–6 weeks vs placebo for secondary prevention | 25,673 adults aged 50–80 years with a history of MI, cerebrovascular disease, peripheral artery disease, or diabetes mellitus with evidence of symptomatic coronary disease; all patients were on statins ± ezetimibe. No lipid level-based inclusion criteria. | Major vascular events (non-fatal MI, death from coronary causes, stroke of any type, or coronary or non-coronary revascularization) | No | RR 0.96; 95% CI 0.90–1.03; P = 0.29 |
| Trials of Fibrates | |||||
| FIELD [9] | Fenofibrate 200 mg micronized per day vs placebo for primary prevention | 9795 adults aged 50–75 years with type 2 diabetes and not using a statin or other lipid-modifying drugs; total cholesterol 116–251 mg/dL, plus either a total cholesterol/HDL-C ratio of ≥4.0:1 or TG 88.6–442.9 mg/dL | First occurrence of non-fatal MI or death from CHD | No | HR 0.89; 95% CI 0.75–1.05; P = 0.16 |
| ACCORD Lipid [8] | Fenofibrate 160 mg/day initially (later adjusted to eGFR) + simvastatin vs placebo + simvastatin | 5518 adults with type 2 diabetes aged 40–79 years if evidence of clinical CV disease, or aged 55–79 years if evidence of subclinical CV disease or at least 2 additional risk factors; LDL-C 60–180 mg/dL and HDL-C <55 mg/dL for women and African-American patients (<50 mg/dL for all other groups) | First occurrence of major CV event, including non-fatal MI, non-fatal stroke, or death from CV causes | No | HR 0.92; 95% CI 0.79–1.08; P = 0.32 |
| BIP [43] | Bezafibrate 400 mg/day vs placebo | 3122 adults aged 45–74 years with a history of MI ≥ 6 months to <5 years before enrollment, and/or stable angina pectoris with total serum cholesterol 180–250 mg/dL, LDL-C ≤180 mg/dL (≤160 mg/dL for patients <50 years of age), HDL-C ≤45 mg/dL, and TG ≤ 300 mg/dL; excluded patients using lipid-modifying drugs | Fatal MI, non-fatal MI, or sudden death | No | 9.4% risk reduction; P = 0.26 |
ACCORD, Action to Control Cardiovascular Risk in Diabetes; ACS, acute coronary syndrome; AIM-HIGH, Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes; BIP, Bezafibrate Infarction Prevention; CHD, coronary heart disease; CI, confidence interval; CV, cardiovascular; ER, extended release; FIELD, Fenofibrate Intervention and Event Lowering in Diabetes; HDL-C, high-density lipoprotein cholesterol; HPS2-THRIVE, Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events; HR, hazard ratio; LDL-C, low-density lipoprotein cholesterol; MI, myocardial infarction; RR, rate ratio; TG, triglycerides.