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

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)