TY  - JOUR
A1  - Bittner, Vera A.
A1  - Szarek, Michael
A1  - Aylward, Philip E.
A1  - Bhatt, Deepak L.
A1  - Diaz, Rafael
A1  - Edelberg, Jay M.
A1  - Fras, Zlatko
A1  - Goodman, Shaun G.
A1  - Halvorsen, Sigrun
A1  - Hanotin, Corinne
A1  - Harrington, Robert A.
A1  - Jukema, J. Wouter
A1  - Loizeau, Virginie
A1  - Moriarty, Patrick M.
A1  - Moryusef, Angèle
A1  - Pordy, Robert
A1  - Roe, Matthew T.
A1  - Sinnaeve, Peter
A1  - Tsimikas, Sotirios
A1  - Vogel, Robert
A1  - White, Harvey D.
A1  - Zahger, Doron
A1  - Zeiher, Andreas M.
A1  - Schwartz, Gregory G.
T1  - Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome
T2  - Journal of the American College of Cardiology
N2  - Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C).
Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE).
Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina.

Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081).
Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).
KW  - acute coronary syndromes
KW  - alirocumab
KW  - low-density lipoprotein cholesterol
KW  - major adverse cardiovascular events
KW  - proprotein convertase subtilisin/kexin type 9 inhibition
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/55154
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-551543
SN  - 0735-1097
N1  - This is an open access article under the CC BY-NC-ND license
VL  - 75
IS  - 2
SP  - 133
EP  - 144
PB  - Elsevier
CY  - Amsterdam [u.a.]
ER  -