TY - JOUR
T1 - Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia
AU - Duell, P. Barton
AU - Santos, Raul D.
AU - Kirwan, Bridget Anne
AU - Witztum, Joseph L.
AU - Tsimikas, Sotirios
AU - Kastelein, John J.P.
N1 - Funding Information:
Drs Tsimikas and Witztum are co-inventors of and receive royalties from patents or patent applications owned by the University of California San Diego on antibodies for biotheranostic applications. Dr Tsimikas has a dual appointment at UCSD and Ionis Pharmaceuticals, Inc. Dr Witztum has received honoraria for consulting for Ionis, CymaBay, and Intercept Pharmaceuticals. Dr Duell has received grants from Genzyme , Retrophin , Regeneron , Amgen and consulting honoraria from Genzyme/Sanofi, Retrophin, Regeneron, and Kaneka. Dr Santos has received a grant from Genzyme and consulting fees from Amgen, Aegerion, Astra Zeneca, Biolab, Boehringer-Ingelheim, Cerenis, Eli Lilly, Genzyme, Kowa, Pfizer, Sanofi/Regeneron, Torrent, and Unilever. Dr Kastelein is a consultant to and receives honoraria from AstraZeneca, Eli Lilly and Company, Amgen, Sanofi, Regeneron, Genzyme, Ionis, Aegerion, and KOWA. Dr Kirwan has no conflicts to disclose.
Publisher Copyright:
© 2016 National Lipid Association
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Background Familial hypercholesterolemia (FH) is characterized by severely elevated LDL-cholesterol and up to a 20-fold increase in premature cardiovascular disease (CVD). Objective Mipomersen has been shown to lower the levels of these atherogenic lipoproteins, but whether it lowers major adverse cardiac events (MACEs) has not been addressed. Methods This post hoc analysis of prospectively collected data of three randomized trials and an open-label extension phase included patients that were exposed to ≥12 months of mipomersen. MACE rates that occurred during 24 months before randomization in the mipomersen group were compared to MACE rates after initiation of mipomersen. Data from the trials included in this report are registered in Clinicaltrials.gov (NCT00607373, NCT00706849, NCT00794664, NCT00694109). The occurrence of MACE events, defined as cardiovascular death, nonfatal acute myocardial infarction, hospitalization for unstable angina, coronary revascularization and nonfatal ischemic stroke, was obtained from medical history data pre-treatment and adjudicated by an independent adjudication committee for events occurring post-treatment with mipomersen. Results MACEs were identified in 61.5% of patients (64 patients with 146 events [39 myocardial infarctions, 99 coronary revascularizations, 5 unstable angina episodes, 3 ischemic strokes]) during 24 months before mipomersen treatment, and in 9.6% of patients (10 patients with 13 events [1 cardiovascular death, 2 myocardial infarctions, 6 coronary interventions, 4 unstable angina episodes]) during a mean of 24.4 months after initiation of mipomersen (MACE rate 25.7 of 1000 patient-months vs 3.9 of 1000 patient-months, OR = 0.053 [95% CI, 0.016–0.168], P < .0001 by the exact McNemar test). The reduction in MACE coincided with a mean absolute reduction in LDL-C of 70 mg/dL (−28%) and of non-HDL cholesterol of 74 mg/dL (−26%) as well as reduction in Lp(a) of 11 mg/dL (−17%). Conclusion Long-term mipomersen treatment not only lowers levels of atherogenic lipoproteins but may also lead to a reduction in cardiovascular events in FH patients.
AB - Background Familial hypercholesterolemia (FH) is characterized by severely elevated LDL-cholesterol and up to a 20-fold increase in premature cardiovascular disease (CVD). Objective Mipomersen has been shown to lower the levels of these atherogenic lipoproteins, but whether it lowers major adverse cardiac events (MACEs) has not been addressed. Methods This post hoc analysis of prospectively collected data of three randomized trials and an open-label extension phase included patients that were exposed to ≥12 months of mipomersen. MACE rates that occurred during 24 months before randomization in the mipomersen group were compared to MACE rates after initiation of mipomersen. Data from the trials included in this report are registered in Clinicaltrials.gov (NCT00607373, NCT00706849, NCT00794664, NCT00694109). The occurrence of MACE events, defined as cardiovascular death, nonfatal acute myocardial infarction, hospitalization for unstable angina, coronary revascularization and nonfatal ischemic stroke, was obtained from medical history data pre-treatment and adjudicated by an independent adjudication committee for events occurring post-treatment with mipomersen. Results MACEs were identified in 61.5% of patients (64 patients with 146 events [39 myocardial infarctions, 99 coronary revascularizations, 5 unstable angina episodes, 3 ischemic strokes]) during 24 months before mipomersen treatment, and in 9.6% of patients (10 patients with 13 events [1 cardiovascular death, 2 myocardial infarctions, 6 coronary interventions, 4 unstable angina episodes]) during a mean of 24.4 months after initiation of mipomersen (MACE rate 25.7 of 1000 patient-months vs 3.9 of 1000 patient-months, OR = 0.053 [95% CI, 0.016–0.168], P < .0001 by the exact McNemar test). The reduction in MACE coincided with a mean absolute reduction in LDL-C of 70 mg/dL (−28%) and of non-HDL cholesterol of 74 mg/dL (−26%) as well as reduction in Lp(a) of 11 mg/dL (−17%). Conclusion Long-term mipomersen treatment not only lowers levels of atherogenic lipoproteins but may also lead to a reduction in cardiovascular events in FH patients.
KW - Antisense
KW - Familial hypercholesterolemia
KW - LDL-Cholesterol
KW - Major adverse cardiovascular events
KW - Mipomersen
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U2 - 10.1016/j.jacl.2016.04.013
DO - 10.1016/j.jacl.2016.04.013
M3 - Article
C2 - 27578134
AN - SCOPUS:84978529098
SN - 1933-2874
VL - 10
SP - 1011
EP - 1021
JO - Journal of clinical lipidology
JF - Journal of clinical lipidology
IS - 4
ER -