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Randomized Controlled Trial
. 2018 Sep 1;3(9):806-814.
doi: 10.1001/jamacardio.2018.2112.

Effect of Infusion of High-Density Lipoprotein Mimetic Containing Recombinant Apolipoprotein A-I Milano on Coronary Disease in Patients With an Acute Coronary Syndrome in the MILANO-PILOT Trial: A Randomized Clinical Trial

Stephen J Nicholls  1   2 , Rishi Puri  2 , Christie M Ballantyne  3   4 , J Wouter Jukema  5 , John J P Kastelein  6 , Wolfgang Koenig  7   8   9 , R Scott Wright  10 , David Kallend  11 , Peter Wijngaard  11 , Marilyn Borgman  2 , Kathy Wolski  2 , Steven E Nissen  2
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Free PMC article
Randomized Controlled Trial

Effect of Infusion of High-Density Lipoprotein Mimetic Containing Recombinant Apolipoprotein A-I Milano on Coronary Disease in Patients With an Acute Coronary Syndrome in the MILANO-PILOT Trial: A Randomized Clinical Trial

Stephen J Nicholls et al. JAMA Cardiol. .
Free PMC article

Abstract

Importance: Infusing a high-density lipoprotein mimetic containing apolipoprotein A-I Milano demonstrated potential atheroma regression in patients following an acute coronary syndrome. To our knowledge, the effect of infusing a new mimetic preparation (MDCO-216) with contemporary statin therapy is unknown.

Objective: To determine the effect of infusing MDCO-216 on coronary atherosclerosis progression.

Design, setting, and participants: This double-blind, randomized clinical trial conducted in 22 hospitals in Canada and Europe compared the effects of 5 weekly intravenous infusions of MDCO-216 at a dose of 20 mg/kg weekly (n = 59) with placebo (n = 67) in statin-treated patients with an acute coronary syndrome.

Main outcomes and measures: The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to day 36 as measured by serial intravascular ultrasonography. The secondary efficacy measures were the nominal changes in normalized total atheroma volume (TAV), atheroma volume in the most diseased 10-mm segment, and the percentage of patients who demonstrated plaque regression. Safety and tolerability were also evaluated.

Results: Among 122 randomized patients (mean [SD] age, 61.8 [10.4] years; 93 men [76.2%]; 61 [50.0%] with prior statin use; and a mean [SD] low-density lipoprotein cholesterol [LDL-C] level of 87.6 [40.5] mg/dL [to convert to millimoles per liter, multiply by 0.0259]), 113 (92.6%) had evaluable imaging results at follow-up. The receiving-treatment LDL-C levels were comparable with the placebo and MDCO-216 (68.6 vs 70.5 mg/dL; difference, -2.5 mg/dL; 95% CI, -10.1 to 5.0; P = .51). A reduction in high-density lipoprotein cholesterol levels was observed in MDCO, but not placebo patients (-3.3 vs 3.0 mg/dL [to convert to millimoles per liter, multiply by 0.0259]; difference, -6.3 mg/dL; 95% CI, -8.5 to -4.1; P < .001). Percent atheroma volume, which was adjusted for baseline values, decreased 0.94% with the placebo and 0.21% with MDCO-216 (difference, 0.73%; 95% CI, -0.07 to 1.52; P = .07). Normalized TAV decreased 7.9 mm3 with the placebo and 6.4 mm3 with MDCO-216 (difference, 1.6 mm3; 95% CI, -5.6 to 8.7; P = .67), and atheroma volume in the most diseased segment decreased 1.8 mm3 with the placebo and 2.2 mm3 with MDCO-216 (difference 0.4 mm3; 95% CI, -4.4 to 3.5; P = .83). A similar percentage of patients demonstrated a regression of PAV (67.2% vs 55.8%; P = .21) and TAV (68.9% vs 71.2%; P = .79) in the placebo and MDCO-216 groups, respectively.

Conclusions and relevance: Among patients with an acute coronary syndrome, infusing MDCO-216 did not produce an incremental plaque regression in the setting of contemporary statin therapy.

Trial registration: ClinicalTrials.gov Identifier: NCT02678923.

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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Nicholls reports receiving research support from AstraZeneca, Amgen Inc, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi Regeneron, and LipoScience and consulting and honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr Puri received consulting fees from Cerenis, Sanofi Aventis, and Amgen Inc. Dr Ballantyne received grant/research support (all significant [>$10 000] and paid to her institution) from Abbott Diagnostic, Amarin, Amgen Inc, Esperion, Ionis, Novartis, Pfizer, Regeneron, Roche Diagnostic, Sanofi-Synthelabo, the National Institutes of Health, the American Heart Association, and the American Dental Association and received consulting fees from Abbott Diagnostics, Amarin, Amgen Inc, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Esperion, Ionis, Matinas BioPharma Inc, Merck, Novartis, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. Dr Jukema has received research grant support from and/or was a speaker (with or without lecture fees) at continuing medical education–credited meetings that were sponsored by Amgen, Anthera, AstraZeneca, Biotronik, Boston Scientific, Daiichi Sankyo, Lilly, Medtronic, Merck-Schering-Plough, Pfizer, Sanofi Aventis, The Medicine Company, the Netherlands Heart Foundation, CardioVascular Research the Netherlands, the Interuniversity Cardiology Institute of the Netherlands, and the European Community Framework KP7 Programme. Dr Kastelein received personal consulting fees from Sanofi, Affiris, Akarna Therapeutics, Amgen Inc, CSL Behring, Regeneron, Staten Biotech, Madrigal, The Medicines Company, Kowa, Lilly, Esperion, Gemphire, Ionis Pharmaceuticals, and Akcea Pharmaceuticals. Dr Koenig reports receiving personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, GSK, DalCor, Sanofi, Berlin-Chemie, Kowa, and Amgen and grants and nonfinancial support from Roche Diagnostics, Beckmann, Singulex, and Abbott. Dr Wright is a consultant for The Medicines Company, Boehringer-Ingelheim, AstraZeneca, Sanofi Regeneron, and Gilead. Drs Kallend and Wijngaard are employees of The Medicines Company. Dr Nissen reports that the Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from Abbvie, AstraZeneca, Amgen Inc, Cerenis, Eli Lilly, Esperion, Pfizer, The Medicines Company, Takeda, and Orexigen. Dr Nissen is involved in these clinical trials, but receives no personal remuneration for his participation. Dr Nissen consults for many pharmaceutical companies, but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction. No other disclosures are reported.

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Figure.
Figure.. Flow Diagram of Patients Throughout the Trial
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