Skip to main content

Table 1 Recent trials investigating effects of fibrates, niacin or omega-3 fatty acids added to statin on residual cardiovascular risk

From: Residual macrovascular risk in 2013: what have we learned?

Treatment/Trial [reference] Daily dose (mg) Patient criteria Duration of follow-up Key findings
Fenofibrate     
ACCORD Lipid (n = 5,518) [46] 1601 Type 2 diabetes; Mean LDL-C ~2.07 mmol/L [80 mg/dL] on simvastatin (mean dose 22.4 mg/day) 4.7 years • No significant benefit on any CV outcomes for the total study population
• For patients with marked atherogenic dyslipidaemia,2 there was ~30% reduction in the primary CV outcome versus simvastatin alone (12.4% versus 17.3%, p = 0.06 for interaction versus all other patients)
Niacin     
AIM-HIGH (n = 3,414) [61, 62] ER niacin titrating to 1500-2000 Patients with CVD with persistent atherogenic dyslipidaemia3 Prematurely terminated; mean 3 years • No significant outcomes benefit with ER niacin
• Methodological issues; inadequately powered, placebo contained a low-dose of niacin (50 mg/capsule), imbalance in concomitant LDL-C lowering therapy between groups
Median LDL-C on statin 1.91 mmol/L [74 mg/dL]
     • For patients with marked atherogenic dyslipidaemia,4 there was a 36% relative reduction in the primary CV outcome (25.0% versus 16.7%, p = 0.032)
HPS2-THRIVE (n = 25,673) [63] ER niacin/laropiprant 2000 Patients with history of CVD Median 3.9 years • No significant outcomes benefit with ER niacin/laropiprant
Mean lipid values at end of pre-randomisation phase (simvastatin 40 mg/day ± ezetimibe):
• Significant increases in diabetic complications, new-onset diabetes, infection, gastrointestinal effects (p < 0.0001), musculoskeletal, bleeding effects (p < 0.001) and skin adverse events (p = 0.026) with ER niacin/laropiprant
LDL-C 1.64 mmol/L [63 mg/dL]
HDL-C 1.14 mmol/L [44 mg/dL]
TG 1.43 mmol/L [125 mg/dL]
Omega-3 fatty acids     
JELIS (n = 18, 645) [65, 66] 1800, EPA High-risk patients with hypercholesterolaemia (total cholesterol ≥6.5 mmol/L [250 mg/dL]) Mean 4.6 years • 19% reduction in major coronary events (2.8% versus 3.5%, p = 0.011) with EPA + statin versus statin alone
Baseline mean LDL-C 4.6 mmol/L [180 mg/dL] on pravastatin 10 mg/day or simvastatin 5 mg/day • A post hoc analysis showed a 53% relative reduction (p = 0.043) in patients with TG ≥1.7 mmol/L (150 mg/dL) and HDL-C <1.0 mmol/L (40 mg/dL) versus those without this dyslipidaemia
ALPHA-OMEGA (n = 4,837) [67] 400, EPA + DHA; MI survivors, 85% on lipid-lowering therapy (mainly statins) 40 months • No significant effect on CV outcomes with any treatment versus placebo (best evidence-based treatment)
2 g ALA; or both
Mean baseline lipids were
LDL-C 2.6 mmol/L [100 mg/dL]
HDL-C 1.28 mmol/L [49.5 mg/dL]
Median TG 1.69 mmol/L [150 mg/dL]
ORIGIN 900 (465 EPA and 375 DHA) Patients with or at risk of diabetes and at high CV risk Median 6.2 years • No significant effect on primary outcome (CV death) or secondary or other clinical outcomes
(n = 12,536) [68]
Mean baseline lipids were
TC 4.9 mmol/L (190 mg/dL)
LDL-C 2.89 mmol/L (112 mg/dL)
HDL-C 1.19 mmol/L (46 mg/dL)
Median TG 1.58 mmol/L (140 mg/dL)
  1. 1Dose at start of trial, subsequently adjusted according to estimated glomerular filtration rate using the abbreviated Modification of Diet in Renal Disease equation; 2Marked atherogenic dyslipidaemia defined as baseline triglycerides in the upper third of the population (≥204 mg/dL or 2.3 mmol/L) and baseline HDL cholesterol levels in the lower third (≤34 mg/dL or 0.9 mmol/L); 3Atherogenic dyslipidaemia defined as median HDL-C 0.91 mmol/L [35 mg/dL] and median triglycerides 1.82 mmol/L [161 mg/dL]; 4Marked atherogenic dyslipidaemia defined as triglycerides >200 mg/dL or 2.3 mmol/L and HDL-C <32 mg/dL or 0.83 mmol/L.
  2. ACCORD Action to Control Cardiovascular Risk In Diabetes; AIM-HIGH Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes; HPS2-THRIVE Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events; JELIS Japan Eicosapentaenoic acid Lipid Intervention Study; ORIGIN Outcome Reduction with an Initial Glargine Intervention; ALA alpha-linolenic acid; CV cardiovascular; CVD cardiovascular disease; DHA docosahexaenoic acid EPA eicosapentaenoic acid; ER extended-release; HDL-C high-density lipoprotein cholesterol; LDL-C low-density lipoprotein cholesterol; MI myocardial infarction; TC total cholesterol; TG triglycerides.