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, Rishi Puri, Christie M. Ballantyne, J. Wouter Jukema, John J.P. Kastelein, Wolfgang Koenig, R. Scott Wright, David Kallend, Peter Wijngaard, Marilyn Borgman, Kathy Wolski, Steven E. Nissen

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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 infusingMDCO-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 20mg/kg weekly (n = 59) with placebo (n = 67) in statin-treated patients with an acute coronary syndrome. MAIN OUTCOMES AND MEASURES The primary efficacy measurewas the nominal change in percent atheroma volume (PAV) from baseline to day 36 as measured by serial intravascular ultrasonography. The secondary efficacy measureswere the nominal changes in normalized total atheroma volume (TAV), atheroma volume in the most diseased 10-mm segment, and the percentage of patientswhodemonstrated plaque regression. Safety and tolerabilitywere also evaluated. RESULTS Among 122 randomized patients (mean [SD] age, 61.8 [10.4] years; 93men[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 by0.0259]), 113 (92.6%) had evaluable imaging results at follow-up. The receiving-treatment LDL-C levelswere comparable with the placebo andMDCO-216 (68.6 vs 70.5mg/dL; difference, -2.5mg/dL; 95%CI, -10.1 to 5.0; P = .51).Areduction in high-density lipoprotein cholesterol levelswas observed inMDCO, but not placebo patients (-3.3 vs 3.0mg/dL [to convert to millimoles per liter, multiply by0.0259]; difference, -6.3mg/dL; 95%CI, -8.5 to -4.1; P < .001). Percent atheroma volume, whichwas adjusted for baseline values, decreased0.94%with the placebo and0.21% withMDCO-216 (difference,0.73%; 95%CI, -0.07 to 1.52; P = .07). Normalized TAVdecreased 7.9mm3 with the placebo and 6.4mm3 withMDCO-216 (difference, 1.6mm3; 95%CI, -5.6 to 8.7; P = .67), and atheroma volume in the most diseased segment decreased 1.8mm3 with the placebo and 2.2mm3 with MDCO-216 (difference0.4mm3; 95%CI, -4.4 to 3.5; P = .83).Asimilar 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 andMDCO-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.

LanguageEnglish
Pages806-814
Number of pages9
JournalJAMA Cardiology
Volume3
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Nicholls, Stephen J. ; Puri, Rishi ; Ballantyne, Christie M. ; Jukema, J. Wouter ; Kastelein, John J.P. ; Koenig, Wolfgang ; Wright, R. Scott ; Kallend, David ; Wijngaard, Peter ; Borgman, Marilyn ; Wolski, Kathy ; Nissen, Steven E. / 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. In: JAMA Cardiology. 2018 ; Vol. 3, No. 9. pp. 806-814.
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title = "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",
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 infusingMDCO-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 20mg/kg weekly (n = 59) with placebo (n = 67) in statin-treated patients with an acute coronary syndrome. MAIN OUTCOMES AND MEASURES The primary efficacy measurewas the nominal change in percent atheroma volume (PAV) from baseline to day 36 as measured by serial intravascular ultrasonography. The secondary efficacy measureswere the nominal changes in normalized total atheroma volume (TAV), atheroma volume in the most diseased 10-mm segment, and the percentage of patientswhodemonstrated plaque regression. Safety and tolerabilitywere also evaluated. RESULTS Among 122 randomized patients (mean [SD] age, 61.8 [10.4] years; 93men[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 by0.0259]), 113 (92.6{\%}) had evaluable imaging results at follow-up. The receiving-treatment LDL-C levelswere comparable with the placebo andMDCO-216 (68.6 vs 70.5mg/dL; difference, -2.5mg/dL; 95{\%}CI, -10.1 to 5.0; P = .51).Areduction in high-density lipoprotein cholesterol levelswas observed inMDCO, but not placebo patients (-3.3 vs 3.0mg/dL [to convert to millimoles per liter, multiply by0.0259]; difference, -6.3mg/dL; 95{\%}CI, -8.5 to -4.1; P < .001). Percent atheroma volume, whichwas adjusted for baseline values, decreased0.94{\%}with the placebo and0.21{\%} withMDCO-216 (difference,0.73{\%}; 95{\%}CI, -0.07 to 1.52; P = .07). Normalized TAVdecreased 7.9mm3 with the placebo and 6.4mm3 withMDCO-216 (difference, 1.6mm3; 95{\%}CI, -5.6 to 8.7; P = .67), and atheroma volume in the most diseased segment decreased 1.8mm3 with the placebo and 2.2mm3 with MDCO-216 (difference0.4mm3; 95{\%}CI, -4.4 to 3.5; P = .83).Asimilar 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 andMDCO-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.",
author = "Nicholls, {Stephen J.} and Rishi Puri and Ballantyne, {Christie M.} and Jukema, {J. Wouter} and Kastelein, {John J.P.} and Wolfgang Koenig and Wright, {R. Scott} and David Kallend and Peter Wijngaard and Marilyn Borgman and Kathy Wolski and Nissen, {Steven E.}",
year = "2018",
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doi = "10.1001/jamacardio.2018.2112",
language = "English",
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journal = "JAMA Cardiology",
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Nicholls, SJ, Puri, R, Ballantyne, CM, Jukema, JW, Kastelein, JJP, Koenig, W, Wright, RS, Kallend, D, Wijngaard, P, Borgman, M, Wolski, K & Nissen, SE 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, vol. 3, no. 9, pp. 806-814. https://doi.org/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. / Nicholls, Stephen J.; Puri, Rishi; Ballantyne, Christie M.; Jukema, J. Wouter; Kastelein, John J.P.; Koenig, Wolfgang; Wright, R. Scott; Kallend, David; Wijngaard, Peter; Borgman, Marilyn; Wolski, Kathy; Nissen, Steven E.

In: JAMA Cardiology, Vol. 3, No. 9, 01.09.2018, p. 806-814.

Research output: Contribution to journalArticle

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

T2 - JAMA Cardiology

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 - 2018/9/1

Y1 - 2018/9/1

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 infusingMDCO-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 20mg/kg weekly (n = 59) with placebo (n = 67) in statin-treated patients with an acute coronary syndrome. MAIN OUTCOMES AND MEASURES The primary efficacy measurewas the nominal change in percent atheroma volume (PAV) from baseline to day 36 as measured by serial intravascular ultrasonography. The secondary efficacy measureswere the nominal changes in normalized total atheroma volume (TAV), atheroma volume in the most diseased 10-mm segment, and the percentage of patientswhodemonstrated plaque regression. Safety and tolerabilitywere also evaluated. RESULTS Among 122 randomized patients (mean [SD] age, 61.8 [10.4] years; 93men[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 by0.0259]), 113 (92.6%) had evaluable imaging results at follow-up. The receiving-treatment LDL-C levelswere comparable with the placebo andMDCO-216 (68.6 vs 70.5mg/dL; difference, -2.5mg/dL; 95%CI, -10.1 to 5.0; P = .51).Areduction in high-density lipoprotein cholesterol levelswas observed inMDCO, but not placebo patients (-3.3 vs 3.0mg/dL [to convert to millimoles per liter, multiply by0.0259]; difference, -6.3mg/dL; 95%CI, -8.5 to -4.1; P < .001). Percent atheroma volume, whichwas adjusted for baseline values, decreased0.94%with the placebo and0.21% withMDCO-216 (difference,0.73%; 95%CI, -0.07 to 1.52; P = .07). Normalized TAVdecreased 7.9mm3 with the placebo and 6.4mm3 withMDCO-216 (difference, 1.6mm3; 95%CI, -5.6 to 8.7; P = .67), and atheroma volume in the most diseased segment decreased 1.8mm3 with the placebo and 2.2mm3 with MDCO-216 (difference0.4mm3; 95%CI, -4.4 to 3.5; P = .83).Asimilar 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 andMDCO-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.

AB - 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 infusingMDCO-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 20mg/kg weekly (n = 59) with placebo (n = 67) in statin-treated patients with an acute coronary syndrome. MAIN OUTCOMES AND MEASURES The primary efficacy measurewas the nominal change in percent atheroma volume (PAV) from baseline to day 36 as measured by serial intravascular ultrasonography. The secondary efficacy measureswere the nominal changes in normalized total atheroma volume (TAV), atheroma volume in the most diseased 10-mm segment, and the percentage of patientswhodemonstrated plaque regression. Safety and tolerabilitywere also evaluated. RESULTS Among 122 randomized patients (mean [SD] age, 61.8 [10.4] years; 93men[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 by0.0259]), 113 (92.6%) had evaluable imaging results at follow-up. The receiving-treatment LDL-C levelswere comparable with the placebo andMDCO-216 (68.6 vs 70.5mg/dL; difference, -2.5mg/dL; 95%CI, -10.1 to 5.0; P = .51).Areduction in high-density lipoprotein cholesterol levelswas observed inMDCO, but not placebo patients (-3.3 vs 3.0mg/dL [to convert to millimoles per liter, multiply by0.0259]; difference, -6.3mg/dL; 95%CI, -8.5 to -4.1; P < .001). Percent atheroma volume, whichwas adjusted for baseline values, decreased0.94%with the placebo and0.21% withMDCO-216 (difference,0.73%; 95%CI, -0.07 to 1.52; P = .07). Normalized TAVdecreased 7.9mm3 with the placebo and 6.4mm3 withMDCO-216 (difference, 1.6mm3; 95%CI, -5.6 to 8.7; P = .67), and atheroma volume in the most diseased segment decreased 1.8mm3 with the placebo and 2.2mm3 with MDCO-216 (difference0.4mm3; 95%CI, -4.4 to 3.5; P = .83).Asimilar 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 andMDCO-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.

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DO - 10.1001/jamacardio.2018.2112

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JO - JAMA Cardiology

JF - JAMA Cardiology

SN - 2380-6583

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