TY - JOUR
T1 - Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol
AU - ODYSSEY Outcomes Committees and Investigators
AU - Schwartz, Gregory G.
AU - Szarek, Michael
AU - Bittner, Vera A.
AU - Diaz, Rafael
AU - Goodman, Shaun G.
AU - Jukema, J. Wouter
AU - Landmesser, Ulf
AU - López-Jaramillo, Patricio
AU - Manvelian, Garen
AU - Pordy, Robert
AU - Scemama, Michel
AU - Sinnaeve, Peter R.
AU - White, Harvey D.
AU - Steg, Ph Gabriel
AU - Bhatt, Deepak L.
AU - Harrington, Robert A.
AU - Zeiher, Andreas M.
AU - Tricoci, Pierluigi
AU - Roe, Matthew T.
AU - Mahaffey, Kenneth W.
AU - Edelberg, Jay M.
AU - Hanotin, Corinne
AU - Lecorps, Guillaume
AU - Moryusef, Angèle
AU - Sasiela, William J.
AU - Tamby, Jean François
AU - Aylward, Philip E.
AU - Drexel, Heinz
AU - Dilic, Mirza
AU - Lopes, Renato D.
AU - Gotcheva, Nina N.
AU - Prieto, Juan Carlos
AU - Yong, Huo
AU - Pećin, Ivan
AU - Reiner, Zeljko
AU - Ostadal, Petr
AU - Poulsen, Steen Hvitfeldt
AU - Viigimaa, Margus
AU - Nieminen, Markku S.
AU - Danchin, Nicolas
AU - Chumburidze, Vakhtang
AU - Marx, Nikolaus
AU - Liberopoulos, Evangelos
AU - Montenegro Valdovinos, Pablo Carlos
AU - Tse, Hung Fat
AU - Kiss, Robert Gabor
AU - Xavier, Denis
AU - Zahger, Doron
AU - Hasin, Yonathan
AU - Rozenman, Yoseph
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/8/3
Y1 - 2021/8/3
N2 - Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). Results: In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (Pinteraction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated.
AB - Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). Results: In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (Pinteraction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated.
KW - PCSK9 inhibitor
KW - acute coronary syndrome
KW - lipoprotein(a)
KW - low-density lipoprotein cholesterol
UR - http://www.scopus.com/inward/record.url?scp=85110291084&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2021.04.102
DO - 10.1016/j.jacc.2021.04.102
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C2 - 34325831
AN - SCOPUS:85110291084
SN - 0735-1097
VL - 78
SP - 421
EP - 433
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 5
ER -