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Original Investigation
July 25, 2018

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 TrialA Randomized Clinical Trial

Author Affiliations
  • 1South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia
  • 2Department of Cardiovascular Medicine and Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio
  • 3Section of Cardiovascular Research, Baylor College of Medicine, Houston, Texas
  • 4Methodist DeBakey Heart and Vascular Center, Houston, Texas
  • 5Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
  • 6Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
  • 7Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
  • 8Deutsches Zentrum für Herz-Kreislauf-Forschung E.V., partner site Munich Heart Alliance, Munich, Germany
  • 9Department of Internal Medicine, University of Ulm Medical Center, Ulm, Germany
  • 10Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
  • 11The Medicines Company, Parsippany, New Jersey
JAMA Cardiol. Published online July 25, 2018. doi:10.1001/jamacardio.2018.2112
Key Points

Question  Does the infusion of the high-density lipoprotein mimetic MDCO-216 modify coronary atherosclerosis disease progression?

Findings  In this randomized clinical trial, 122 patients with an acute coronary syndrome were treated with weekly intravenous infusions of MDCO-216 or a placebo for 6 weeks and underwent serial intravascular ultrasonography determination of coronary atheroma volume. Infusing MDCO-216 did not promote the regression of coronary atherosclerosis compared with the placebo in statin-treated patients.

Meaning  Adding the high-density lipoprotein mimetic MDCO-216 did not produce plaque regression in statin-treated patients following an acute coronary syndrome.

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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