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ApoA-I Milano on Coronary Atherosclerosis in Acute Coronary Syndromes - ApoA-I Milano on Coronary Atherosclerosis in ACS
Description:
The goal of the trial was to evaluate the effect of intravenous (IV) recombinant ApoA-I Milano/phospholipid complexes (ETC-216) on atheroma burden in patients with acute coronary syndromes (ACSs).
Hypothesis:
Treatment with IV recombinant ApoA-I Milano/phospholipid complexes will be associated with a reduction in atheroma burden in patients with ACSs.
Study Design
Study Design:
Patients Screened: 123
Patients Enrolled: 57; 47 completed follow-up
Mean Follow Up: Five weeks
Mean Patient Age: mean age 57 years
Female: 47
Patient Populations:
Age 30-75 years; diagnostic coronary angiography for clinical indications within 14 days after an ACS, defined as unstable angina, non–ST elevation myocardial infarction (STEMI), or STEMI; presence of an obstructive lesion in a major epicardial vessel with ≥20% luminal diameter narrowing by visual angiographic estimation; and target vessel for IVUS ≤50% luminal narrowing throughout a segment with a minimum length of 30 mm (target segment) and target vessel without previous angioplasty
Primary Endpoints:
Change in percent atheroma volume (follow-up minus baseline)
Secondary Endpoints:
Change in total atheroma volume, change in average maximal atheroma thickness, and change in atheroma volume in the most severely and least severely diseased 10-mm-long subsegments
Drug/Procedures Used:
Patients were randomized in a 1:2:2 ratio to placebo (n=11), low dose ETC-216 (n=21; 15 mg/kg), or high dose ETC-216 (n=15; 45 mg/kg). Study drug was administered at weekly intervals for five doses and was given as an IV infusion. Intravascular ultrasound (IVUS) examination was performed within two weeks of the ACS event and was repeated within two weeks of the final study drug dose.
Concomitant Medications:
Customary standard of care for ACS
Principal Findings:
Percent atheroma volume decreased by a mean of -1.06% in the combined ETC-216 group (median -0.81%; 95% confidence interval [CI] -1.53% to -0.34%; p=0.02 compared with baseline), but did not change in the placebo group (mean increase 0.14%, median 0.03%; 95% CI -1.11% to 1.43%; p=0.97 compared with baseline). The change in total atheroma volume in the combined treatment groups was -14.1 mm3 (p<0.001), while there was no significant change in the placebo arm (-2.9 mm3, p=0.97). Maximum atheroma thickness was -0.042 mm in the combined treatment group (p<0.001 vs. baseline) and -0.008 mm in the placebo group (p=0.83).
There was no difference in the secondary endpoint of mean change in coronary lumen diameter on angiography in either arm (p=0.62 in the combined treatment group and p=0.63 in the placebo group).
Interpretation:
Among patients with ACSs, treatment with recombinant ApoA-I Milano/phospholipid complexes (ETC-216) was associated with a reduction in atheroma burden at follow-up compared with baseline, while similar changes did not occur in the placebo arm. The authors speculate that therapy with a synthetic high-density lipoprotein mimetic may achieve benefit more quickly and produce a greater extent of regression than conventional lipid-lowering therapy.
While provocative, it should be noted that the sample size of the study was small and the trial did not assess ETC-216 compared with placebo in a direct comparison, but rather assessed changes from baseline in each arm separately. A larger, randomized direct comparison trial would be needed to draw conclusions regarding the effect of ETC-216 on clinical endpoints.
References:
Nissen SE, Tsunoda T, Tuzcu EM, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 2003;290:2292-300.
Keywords: Phosphatidylcholines, Coronary Artery Disease, Myocardial Infarction, Acute Coronary Syndrome, Plaque, Atherosclerotic, Coronary Angiography, Apolipoprotein A-I, Lipoproteins, HDL, Angioplasty
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