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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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).

Original languageEnglish (US)
JournalJAMA Cardiology
DOIs
StateAccepted/In press - Jan 1 2018

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Atherosclerotic Plaques
HDL Lipoproteins
Acute Coronary Syndrome
Coronary Disease
Randomized Controlled Trials
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Placebos
LDL Cholesterol
Interventional Ultrasonography
MDCO-216
apolipoprotein A-I Milano
Intravenous Infusions
HDL Cholesterol
Canada
Coronary Artery Disease
Therapeutics
Outcome Assessment (Health Care)
Safety

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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, 01.01.2018.

Research output: Contribution to journalArticle

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.
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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 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).",
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",
month = "1",
day = "1",
doi = "10.1001/jamacardio.2018.2112",
language = "English (US)",
journal = "JAMA Cardiology",
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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 - 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 - 2018/1/1

Y1 - 2018/1/1

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 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).

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 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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