Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial

• To study the effects of intravenous recombinant Apo A-1 Milano/phospholipid complexes (ETC-216) on arterial plaque burden in patients with acute coronary syndromes (ACS).^[1]

• A 5 week, randomized, double-blinded, multicenter, parallel-treatment randomized control trial^[1]
• Patients enrolled: 123 patients
• Patients completed the protocol: 47 patients

IVUS was done at baseline. Intravenous infusion took place weekly for 5 consecutive weeks. Two weeks after infusion, IVUS was repeated for comparison.^[1]

• Age: 30-75 years
• Angiography performed within 14 days following ACS event.
• At least 20% luminal diameter stenosis by visual estimated required
• Intravascular ultrasound (IVUS) done within 14 days of ACS event.
• No more than 50% luminal narrowing in a segment that is at least 30 mm in length.
• No previous percutaneous coronary intervention (PCI)
• Other anti-lipidemic drugs permitted during the study as long as no introduction or new medication or change in dosage occurs within 6 weeks of study start or end date.

Change in percent atheroma volume as measured by IVUS^[1]

Assessment of adverse events, quantitative angiographic changes, change in average maximal thickness or in total volume of atheroma,or atheroma volume change in most and least severely diseases 10-mm-long segments.^[1]

• 10 patients were discontinued, while another 3 elected to discontinue
• 2 patients were withdrawn for adverse events
• 5 had IVUS that could not be analyzed

There was a significant difference in atheroma volume, mean change in total atheroma volume and thickness in the ETC-216 groups (combined) showing a 3.17% difference (p=0.02, p<0.001, p<0.001 respectively).^[1] This statistical significance was not seen in patients on placebo. Most regression using ETC-216 was seen in subsegments of 10 mm long that are severely diseased, in comparison to those with only mild disease (p<0.001).^[1]

However, luminal diameter on angiography was not different when comparing follow-up to baseline or when comparing ETC-216 vs. placebo.^[1]

Adverse events included mainly minor gastrointestinal events, headaches,arthralgias, and edema that were found in all 3 groups. Two important adverse events that required withdrawal were:

• 1 patient with elevated liver function tests 3 times the upper normal limit with nausea vomiting, and cholelithiasis.^[1]
• 1 patient with chills, rigors, rash, nausea, vomiting, and diaphoresis that occurred during infusion.^[1]

Although Apo A-1 Milano infusions resulted in a decrease in plaque burden, further study is required to assess efficacy, safety and cost-effectiveness.^[1]