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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.
JAMA Cardiol. 2018 09 01; 3(9):806-814.JC

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.

Authors+Show Affiliations

South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia. Department of Cardiovascular Medicine and Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.Department of Cardiovascular Medicine and Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.Section of Cardiovascular Research, Baylor College of Medicine, Houston, Texas. Methodist DeBakey Heart and Vascular Center, Houston, Texas.Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.Deutsches Herzzentrum München, Technische Universität München, Munich, Germany. Deutsches Zentrum für Herz-Kreislauf-Forschung E.V., partner site Munich Heart Alliance, Munich, Germany. Department of Internal Medicine, University of Ulm Medical Center, Ulm, Germany.Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.The Medicines Company, Parsippany, New Jersey.The Medicines Company, Parsippany, New Jersey.Department of Cardiovascular Medicine and Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.Department of Cardiovascular Medicine and Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.Department of Cardiovascular Medicine and Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30046837

Citation

Nicholls, Stephen J., et al. "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." JAMA Cardiology, vol. 3, no. 9, 2018, pp. 806-814.
Nicholls SJ, Puri R, Ballantyne CM, et al. 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. JAMA Cardiol. 2018;3(9):806-814.
Nicholls, S. J., Puri, R., Ballantyne, C. M., Jukema, J. W., Kastelein, J. J. P., Koenig, W., Wright, R. S., Kallend, D., Wijngaard, P., Borgman, M., Wolski, K., & Nissen, S. E. (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 Trial: A Randomized Clinical Trial. JAMA Cardiology, 3(9), 806-814. https://doi.org/10.1001/jamacardio.2018.2112
Nicholls SJ, et al. 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. JAMA Cardiol. 2018 09 1;3(9):806-814. PubMed PMID: 30046837.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Nicholls,Stephen J, AU - Puri,Rishi, AU - Ballantyne,Christie M, AU - Jukema,J Wouter, AU - Kastelein,John J P, AU - Koenig,Wolfgang, AU - Wright,R Scott, AU - Kallend,David, AU - Wijngaard,Peter, AU - Borgman,Marilyn, AU - Wolski,Kathy, AU - Nissen,Steven E, PY - 2018/7/27/pubmed PY - 2019/10/8/medline PY - 2018/7/27/entrez SP - 806 EP - 814 JF - JAMA cardiology JO - JAMA Cardiol VL - 3 IS - 9 N2 - 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. SN - 2380-6591 UR - https://www.unboundmedicine.com/medline/citation/30046837/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_ L2 - https://jamanetwork.com/journals/jamacardiology/fullarticle/10.1001/jamacardio.2018.2112 DB - PRIME DP - Unbound Medicine ER -