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|Objective:||This secondary analysis of AIM-HIGH investigated the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes.|
|Study design:||Double-blind randomised placebo-controlled trial|
3414 patients with established stable atherosclerotic disease with HDL-C levels <40 mg/dL (1.03 mmol/L) for men and <50 mg/dL (1.29 mmol/L) for women, high triglycerides (150 to 400 mg/dL or 1.7 to 4.5 mmol/L) and low-density lipoprotein cholesterol (LDL-C) levels <180 mg/dL (4.65 mmol/L). All subjects received simvastatin with or without ezetimibe.
• Major cardiovascular (CV) events, a composite of CV death, myocardial infarction, acute coronary syndrome, ischaemic stroke, or symptom-driven revascularisation
Subjects were randomised to receive once daily extended-release (ER) niacin 1,500 to 2,000 mg or placebo (containing 50 mg per capsule). LDL-C levels in both groups were maintained from 40 to 80 mg/dL. Hazard ratios were estimated by using Cox proportional hazards models for relationships between lipoproteins and the composite CV endpoint.
For the total study population, there was no significant benefit on CV outcomes associated with ER niacin. However, for subjects (n=522, 15.3%) with both baseline triglycerides in the highest tertile (≥198 mg/dL or 2.24 mmol/L) and HDL-C levels in the lowest tertile (<33 mg/dL or 0.85 mmol/L), there was a non-significant trend (p=0.073) toward reduction of CV risk with ER niacin (see Table 1). Additionally, in patients (n=439, 12.9%) with triglyceride levels ≥200 mg/dL (2.23 mmol/L) and HDL-C levels <32 mg/dL (0.83 mmol/L) this trend was stronger (Hazard ratio 0.64, p=0.032).
Table 1. Subgroup analysis of AIM-HIGH according to baseline atherogenic dyslipidaemia
|Authors’ conclusion:||Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-C–lowering therapy, but a small dyslipidaemic subgroup may benefit.|
This subgroup analysis from AIM-HIGH is consistent with data from major prospective fibrate trials showing the clinical benefits of targeting atherogenic dyslipidaemia, the combination of elevated triglycerides and low HDL-C plasma concentration. In a meta-analysis of these trials using similar lipid criteria for atherogenic dyslipidaemia (triglycerides ≥204 mg/dL or 2.3 mmol/L and HDL-C £34 mg/dL or 0.88 mmol/L), there was a 35% relative reduction in CV events, versus 6% in those without this dyslipidaemia.1 Additionally, the proportion of patients with atherogenic dyslipidaemia at baseline in AIM-HIGH was similar to that reported for both ACCORD (Action to Control Cardiovascular Risk in Diabetes) Lipid and the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) studies (17% and 19%, respectively).2,3 However, it is likely that this proportion may have been overestimated, given that this subgroup was defined by tertile analysis.
In conclusion, these findings are consistent with available evidence supporting a lipid-related modifiable component to CV residual risk in statin-treated patients at high CV risk, including those with type 2 diabetes. Irrespective of therapeutic intervention (niacin or fibrate), targeting these high-risk patients with atherogenic dyslipidaemia offers the potential for reduction in residual cardiovascular risk.
1. Sacks FM, Carey VJ, Fruchart JC: Combination lipid therapy in type 2 diabetes. N Engl J Med 2010,363:692-84.
residual cardiovascular risk; atherogenic dyslipidaemia; AIM-HIGH; niacin