Tags

Type your tag names separated by a space and hit enter

Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial.
JAMA. 2003 Nov 05; 290(17):2292-300.JAMA

Abstract

CONTEXT

Although low levels of high-density lipoprotein cholesterol (HDL-C) increase risk for coronary disease, no data exist regarding potential benefits of administration of HDL-C or an HDL mimetic. ApoA-I Milano is a variant of apolipoprotein A-I identified in individuals in rural Italy who exhibit very low levels of HDL. Infusion of recombinant ApoA-I Milano-phospholipid complexes produces rapid regression of atherosclerosis in animal models.

OBJECTIVE

We assessed the effect of intravenous recombinant ApoA-I Milano/phospholipid complexes (ETC-216) on atheroma burden in patients with acute coronary syndromes (ACS).

DESIGN

The study was a double-blind, randomized, placebo-controlled multicenter pilot trial comparing the effect of ETC-216 or placebo on coronary atheroma burden measured by intravascular ultrasound (IVUS).

SETTING

Ten community and tertiary care hospitals in the United States.

PATIENTS

Between November 2001 and March 2003, 123 patients aged 38 to 82 years consented, 57 were randomly assigned, and 47 completed the protocol.

INTERVENTIONS

In a ratio of 1:2:2, patients received 5 weekly infusions of placebo or ETC-216 at 15 mg/kg or 45 mg/kg. Intravascular ultrasound was performed within 2 weeks following ACS and repeated after 5 weekly treatments.

MAIN OUTCOME MEASURES

The primary efficacy parameter was the change in percent atheroma volume (follow-up minus baseline) in the combined ETC-216 cohort. Prespecified secondary efficacy measures included the change in total atheroma volume and average maximal atheroma thickness.

RESULTS

The mean (SD) percent atheroma volume decreased by -1.06% (3.17%) in the combined ETC-216 group (median, -0.81%; 95% confidence interval [CI], -1.53% to -0.34%; P =.02 compared with baseline). In the placebo group, mean (SD) percent atheroma volume increased by 0.14% (3.09%; median, 0.03%; 95% CI, -1.11% to 1.43%; P =.97 compared with baseline). The absolute reduction in atheroma volume in the combined treatment groups was -14.1 mm3 or a 4.2% decrease from baseline (P<.001).

CONCLUSIONS

A recombinant ApoA-I Milano/phospholipid complex (ETC-216) administered intravenously for 5 doses at weekly intervals produced significant regression of coronary atherosclerosis as measured by IVUS. Although promising, these results require confirmation in larger clinical trials with morbidity and mortality end points.

Authors+Show Affiliations

Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. nissens@ccf.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

14600188

Citation

Nissen, Steven E., et al. "Effect of Recombinant ApoA-I Milano On Coronary Atherosclerosis in Patients With Acute Coronary Syndromes: a Randomized Controlled Trial." JAMA, vol. 290, no. 17, 2003, pp. 2292-300.
Nissen SE, Tsunoda T, Tuzcu EM, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003;290(17):2292-300.
Nissen, S. E., Tsunoda, T., Tuzcu, E. M., Schoenhagen, P., Cooper, C. J., Yasin, M., Eaton, G. M., Lauer, M. A., Sheldon, W. S., Grines, C. L., Halpern, S., Crowe, T., Blankenship, J. C., & Kerensky, R. (2003). Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA, 290(17), 2292-300.
Nissen SE, et al. Effect of Recombinant ApoA-I Milano On Coronary Atherosclerosis in Patients With Acute Coronary Syndromes: a Randomized Controlled Trial. JAMA. 2003 Nov 5;290(17):2292-300. PubMed PMID: 14600188.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. AU - Nissen,Steven E, AU - Tsunoda,Taro, AU - Tuzcu,E Murat, AU - Schoenhagen,Paul, AU - Cooper,Christopher J, AU - Yasin,Muhammad, AU - Eaton,Gregory M, AU - Lauer,Michael A, AU - Sheldon,W Scott, AU - Grines,Cindy L, AU - Halpern,Stephen, AU - Crowe,Tim, AU - Blankenship,James C, AU - Kerensky,Richard, PY - 2003/11/6/pubmed PY - 2003/12/3/medline PY - 2003/11/6/entrez SP - 2292 EP - 300 JF - JAMA JO - JAMA VL - 290 IS - 17 N2 - CONTEXT: Although low levels of high-density lipoprotein cholesterol (HDL-C) increase risk for coronary disease, no data exist regarding potential benefits of administration of HDL-C or an HDL mimetic. ApoA-I Milano is a variant of apolipoprotein A-I identified in individuals in rural Italy who exhibit very low levels of HDL. Infusion of recombinant ApoA-I Milano-phospholipid complexes produces rapid regression of atherosclerosis in animal models. OBJECTIVE: We assessed the effect of intravenous recombinant ApoA-I Milano/phospholipid complexes (ETC-216) on atheroma burden in patients with acute coronary syndromes (ACS). DESIGN: The study was a double-blind, randomized, placebo-controlled multicenter pilot trial comparing the effect of ETC-216 or placebo on coronary atheroma burden measured by intravascular ultrasound (IVUS). SETTING: Ten community and tertiary care hospitals in the United States. PATIENTS: Between November 2001 and March 2003, 123 patients aged 38 to 82 years consented, 57 were randomly assigned, and 47 completed the protocol. INTERVENTIONS: In a ratio of 1:2:2, patients received 5 weekly infusions of placebo or ETC-216 at 15 mg/kg or 45 mg/kg. Intravascular ultrasound was performed within 2 weeks following ACS and repeated after 5 weekly treatments. MAIN OUTCOME MEASURES: The primary efficacy parameter was the change in percent atheroma volume (follow-up minus baseline) in the combined ETC-216 cohort. Prespecified secondary efficacy measures included the change in total atheroma volume and average maximal atheroma thickness. RESULTS: The mean (SD) percent atheroma volume decreased by -1.06% (3.17%) in the combined ETC-216 group (median, -0.81%; 95% confidence interval [CI], -1.53% to -0.34%; P =.02 compared with baseline). In the placebo group, mean (SD) percent atheroma volume increased by 0.14% (3.09%; median, 0.03%; 95% CI, -1.11% to 1.43%; P =.97 compared with baseline). The absolute reduction in atheroma volume in the combined treatment groups was -14.1 mm3 or a 4.2% decrease from baseline (P<.001). CONCLUSIONS: A recombinant ApoA-I Milano/phospholipid complex (ETC-216) administered intravenously for 5 doses at weekly intervals produced significant regression of coronary atherosclerosis as measured by IVUS. Although promising, these results require confirmation in larger clinical trials with morbidity and mortality end points. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/14600188/Effect_of_recombinant_ApoA_I_Milano_on_coronary_atherosclerosis_in_patients_with_acute_coronary_syndromes:_a_randomized_controlled_trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/vol/290/pg/2292 DB - PRIME DP - Unbound Medicine ER -