Relationship of Apolipoproteins A-1 and B, and Lipoprotein(a) to Cardiovascular Outcomes: The AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglyceride and Impact on Global Health Outcomes).

Albers JJ, Slee A, O'Brien KD et al.
J Am Coll Cardiol. 2013 Oct 22;62(17):1575-9. doi: 10.1016/j.jacc.2013.06.051

Background

The AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglyceride and Impact on Global Health Outcomes) prospectively evaluated the effect of addition of extended release niacin (ERN) to simvastatin therapy in participants with established atherothrombotic cardiovascular (CV) disease. Addition of ERN did not further reduce the incidence of CV events [1].
This report studies the effect of LDL-lowering therapy (simvastatin with or without ezetimibe) plus ERN, as compared to LDL-lowering therapy alone, on Lp(a), apoA-1 and apoB, and the relationship of their baseline and on-treatment levels to CV outcomes.

Main results

• After 1 year of treatment, the apoB/apoA-1-ratio had decreased by 19% and 7% in respectively the ERN and placebo groups. Lp(a) decreased by 21% in the ERN group, and by 6% in the placebo group, yielding an overall least-square mean decrease in Lp(a) due to ERN of 19%.
• Baseline apoB and apoB/apoA-1 levels were only associated with CV events in the placebo group, but treatment interaction was not statistically significant.
  Lp(a) showed the highest hazard ratios, which were similar in both treatment groups.
• After 1 year, 1 SD higher apoB/apoA-1 ratio was associated with a 21% higher risk of a primary event (P=0.031), while this ratio was not related to CV event risk in the ERN group.
  1 SD higher log Lp(a) gave a HR of 1.21 (P=0.017) in the placebo group, and HR: 1.18 (P=0.028) in the ERN group.
• Similar event rates were seen within each quartile of baseline Lp(a) and in both treatment groups, despite greater decreases in Lp(a) for those taking ERN than in those on placebo.

Conclusion

Subjects randomised to ERN had favourable changes in apoA-I levels, the apoB/apoA-I ratio and Lp(a) levels. Baseline and on-study Lp(a) predicted CV events in both treatment groups. Nevertheless, no subgroup that benefits from ERN therapy was identified based on these variables. Even subjects receiving ERN who were in the highest Lp(a) quartile, did not benefit from the addition of niacin to statin-based therapy.
AIM-HIGH showed that Lp(a) contributes to residual CV risk in patients who achieved target LDL-c levels with statin therapy. This study adds the observation that favourable changes in apolipoproteins and Lp(a) from ERN do not translate to CV event reduction.

References

1. The AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive Statin therapy. N Engl J Med 2011;365: 2255–67.

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