Rationale and Design of ApoA-I Event Reducing in Ischemic Syndromes II (AEGIS-II)

This is a design paper, not a results paper — it lays out the rationale for AEGIS-II, a large trial testing whether boosting cholesterol efflux can prevent recurrent events early after a heart attack.

The intervention, CSL112, is an infusible form of apolipoprotein A-I (the main protein of HDL) intended to enhance the body’s removal of cholesterol from plaques during the high-risk weeks following an acute myocardial infarction. The protocol describes a rigorous phase 3, double-blind, placebo-controlled design in 17,400 patients — a serious test of the “HDL function” hypothesis after the failure of HDL-raising drugs.

As a protocol, it contains no findings; its inclusion documents an important hypothesis being put to a definitive test. (Notably, AEGIS-II later reported a neutral primary result, continuing the long run of disappointments for HDL-targeted therapies.)

We rate the evidence moderate as a design document. Its value is in framing a key question; the answer lies in the completed trial, which did not show the hoped-for benefit — a reminder of how hard the HDL pathway has been to translate into therapy.