AIM-HIGH: potential benefit with niacin in patients with atherogenic dyslipidaemia

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Macrovascular Residual Risk Studies

13 January 2014

Subgroup analyses from the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) study, revealed potential clinical benefit in subjects with both highest baseline triglycerides and lowest baseline high-density lipoprotein cholesterol plasma concentrations.

Guyton JR, Slee AE, Anderson T, Fleg JL, Goldberg RB, Kashyap ML, Marcovina SM, Nash SD, O

STUDY SUMMARY

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

Study population:

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.

Primary variable:

‚Ä¢ Major cardiovascular (CV) events, a composite of CV death, myocardial infarction, acute coronary syndrome, ischaemic stroke, or symptom-driven revascularisation

Methods:

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.

Results:

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 (‚â•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 ‚â•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

	ER niacin	Placebo	HR (95% CI)
All subjects	282/1718 (16.4%)	274/1696 (16.2%)	1.02 (0.87-1.21)
TG ¬≥198 mg/dl and HDL-C<33 mg/dL	48 (17.0%)	54 (22.4%).	0.74 (0.50‚Äì1.09)

Authors‚Äô conclusion:

Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-C‚Äìlowering therapy, but a small dyslipidaemic subgroup may benefit.

COMMENT

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 ‚â•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.

References

1. Sacks FM, Carey VJ, Fruchart JC: Combination lipid therapy in type 2 diabetes. N Engl J Med 2010,363:692-84.
2. ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Eng J Med 2010,362:1563‚Äì74.
3. Scott R, O'Brien R, Fulcher G et al; Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study Investigators: Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care 2009,32:493-8.

Key words

residual cardiovascular risk; atherogenic dyslipidaemia; AIM-HIGH; niacin