Plasma-Derived Apolipoprotein A-I Infusions Are Well-Tolerated, Acutely Increase Cholesterol Efflux Capacity

Human and recombinant apolipoprotein A-I (apoA-I) is the primary functional component of high-density lipoprotein, and has been shown to increase cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. In a Phase IIb, multicenter dose-ranging study, a total of 1,258 patients with myocardial infarction (MI) were randomized to receive, within seven days of their MI event, four consecutive weekly infusions of low or high doses of reconstituted human plasma-derived apoA-I (CSL112; CSL Behring) or placebo. This study was primarily intended to assess the safety and tolerability of CSL112, focusing on markers of hepatic and renal function, but also examined cholesterol efflux.

Four weekly infusions of CSL112 at both low (2 g) and high (6 g) doses were not associated with alterations in either liver or kidney function. Major adverse coronary event rates were generally comparable between groups, although cardiovascular mortality was higher in the 6 g group compared with the placebo group (4 versus 0 deaths; P= 0.0477). The 2 g dose elevated apoA-I 1.29-fold and total cholesterol efflux capacity 1.87-fold, while the 6 g dose elevated them 2.06-fold and 2.45-fold, respectively. The elevation of cholesterol efflux capacity mediated by CSL112 is transient, receding to baseline with clearance of the apoA-I. The investigators concluded that “further assessment of the clinical efficacy of CSL112 for the reduction of early recurrent cardiovascular events after acute MI is warranted in an adequately controlled, multicenter, randomized Phase III trial.”