Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

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Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol. / Schwartz, Gregory G.; Szarek, Michael; Bittner, Vera A.; Diaz, Rafael; Goodman, Shaun G.; Jukema, J. Wouter; Landmesser, Ulf; López-Jaramillo, Patricio; Manvelian, Garen; Pordy, Robert; Scemama, Michel; Sinnaeve, Peter; White, Harvey D.; Gabriel Steg, Ph; Gabriel Steg, P. H.; Bhatt, Deepak L.; Harrington, Robert A.; Zeiher, Andreas M.; Tricoci, Pierluigi; Roe, Matthew T.; Mahaffey, Kenneth W.; Edelberg, Jay M.; Hanotin, Corinne; Lecorps, Guillaume; Moryusef, Angèle; Sasiela, William J.; Tamby, Jean François; Aylward, Philip E.; Drexel, Heinz; Sinnaeve, Peter; Dilic, Mirza; Lopes, Renato D.; Gotcheva, Nina N.; Prieto, Juan Carlos; Yong, Huo; Pećin, Ivan; Reiner, Zeljko; Clemmensen, Peter; Bang, Lia E.; Hove, Jens D.; Gislason, Gunnar; Larsen, John; Johansen, Peter; Jeppesen, Jørgen; Nielsen, Peter Kaiser; Hansen, Ole; Jensen, Steen Agergaard; Rosenberg, Michael; Andersen, Dorthe; ODYSSEY OUTCOMES Committees and Investigators.

I: Journal of the American College of Cardiology, Bind 78, Nr. 5, 2021, s. 421-433.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Schwartz, GG, Szarek, M, Bittner, VA, Diaz, R, Goodman, SG, Jukema, JW, Landmesser, U, López-Jaramillo, P, Manvelian, G, Pordy, R, Scemama, M, Sinnaeve, P, White, HD, Gabriel Steg, P, Gabriel Steg, PH, Bhatt, DL, Harrington, RA, Zeiher, AM, Tricoci, P, Roe, MT, Mahaffey, KW, Edelberg, JM, Hanotin, C, Lecorps, G, Moryusef, A, Sasiela, WJ, Tamby, JF, Aylward, PE, Drexel, H, Sinnaeve, P, Dilic, M, Lopes, RD, Gotcheva, NN, Prieto, JC, Yong, H, Pećin, I, Reiner, Z, Clemmensen, P, Bang, LE, Hove, JD, Gislason, G, Larsen, J, Johansen, P, Jeppesen, J, Nielsen, PK, Hansen, O, Jensen, SA, Rosenberg, M, Andersen, D & ODYSSEY OUTCOMES Committees and Investigators 2021, 'Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol', Journal of the American College of Cardiology, bind 78, nr. 5, s. 421-433. https://doi.org/10.1016/j.jacc.2021.04.102

APA

Schwartz, G. G., Szarek, M., Bittner, V. A., Diaz, R., Goodman, S. G., Jukema, J. W., Landmesser, U., López-Jaramillo, P., Manvelian, G., Pordy, R., Scemama, M., Sinnaeve, P., White, H. D., Gabriel Steg, P., Gabriel Steg, P. H., Bhatt, D. L., Harrington, R. A., Zeiher, A. M., Tricoci, P., ... ODYSSEY OUTCOMES Committees and Investigators (2021). Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol. Journal of the American College of Cardiology, 78(5), 421-433. https://doi.org/10.1016/j.jacc.2021.04.102

Vancouver

Schwartz GG, Szarek M, Bittner VA, Diaz R, Goodman SG, Jukema JW o.a. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol. Journal of the American College of Cardiology. 2021;78(5):421-433. https://doi.org/10.1016/j.jacc.2021.04.102

Author

Schwartz, Gregory G. ; Szarek, Michael ; Bittner, Vera A. ; Diaz, Rafael ; Goodman, Shaun G. ; Jukema, J. Wouter ; Landmesser, Ulf ; López-Jaramillo, Patricio ; Manvelian, Garen ; Pordy, Robert ; Scemama, Michel ; Sinnaeve, Peter ; White, Harvey D. ; Gabriel Steg, Ph ; Gabriel Steg, P. H. ; Bhatt, Deepak L. ; Harrington, Robert A. ; Zeiher, Andreas M. ; Tricoci, Pierluigi ; Roe, Matthew T. ; Mahaffey, Kenneth W. ; Edelberg, Jay M. ; Hanotin, Corinne ; Lecorps, Guillaume ; Moryusef, Angèle ; Sasiela, William J. ; Tamby, Jean François ; Aylward, Philip E. ; Drexel, Heinz ; Sinnaeve, Peter ; Dilic, Mirza ; Lopes, Renato D. ; Gotcheva, Nina N. ; Prieto, Juan Carlos ; Yong, Huo ; Pećin, Ivan ; Reiner, Zeljko ; Clemmensen, Peter ; Bang, Lia E. ; Hove, Jens D. ; Gislason, Gunnar ; Larsen, John ; Johansen, Peter ; Jeppesen, Jørgen ; Nielsen, Peter Kaiser ; Hansen, Ole ; Jensen, Steen Agergaard ; Rosenberg, Michael ; Andersen, Dorthe ; ODYSSEY OUTCOMES Committees and Investigators. / Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol. I: Journal of the American College of Cardiology. 2021 ; Bind 78, Nr. 5. s. 421-433.

Bibtex

@article{bebd7792b26647ce9bf1fdaf8fc29982,

title = "Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol",

abstract = "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. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)",

keywords = "acute coronary syndrome, lipoprotein(a), low-density lipoprotein cholesterol, PCSK9 inhibitor",

author = "Schwartz, {Gregory G.} and Michael Szarek and Bittner, {Vera A.} and Rafael Diaz and Goodman, {Shaun G.} and Jukema, {J. Wouter} and Ulf Landmesser and Patricio L{\'o}pez-Jaramillo and Garen Manvelian and Robert Pordy and Michel Scemama and Peter Sinnaeve and White, {Harvey D.} and {Gabriel Steg}, Ph and {Gabriel Steg}, {P. H.} and Bhatt, {Deepak L.} and Harrington, {Robert A.} and Zeiher, {Andreas M.} and Pierluigi Tricoci and Roe, {Matthew T.} and Mahaffey, {Kenneth W.} and Edelberg, {Jay M.} and Corinne Hanotin and Guillaume Lecorps and Ang{\`e}le Moryusef and Sasiela, {William J.} and Tamby, {Jean Fran{\c c}ois} and Aylward, {Philip E.} and Heinz Drexel and Peter Sinnaeve and Mirza Dilic and Lopes, {Renato D.} and Gotcheva, {Nina N.} and Prieto, {Juan Carlos} and Huo Yong and Ivan Pe{\'c}in and Zeljko Reiner and Peter Clemmensen and Bang, {Lia E.} and Hove, {Jens D.} and Gunnar Gislason and John Larsen and Peter Johansen and J{\o}rgen Jeppesen and Nielsen, {Peter Kaiser} and Ole Hansen and Jensen, {Steen Agergaard} and Michael Rosenberg and Dorthe Andersen and {ODYSSEY OUTCOMES Committees and Investigators}",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

doi = "10.1016/j.jacc.2021.04.102",

language = "English",

volume = "78",

pages = "421--433",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier",

number = "5",

}

RIS

TY - JOUR

T1 - Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

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

AU - White, Harvey D.

AU - Gabriel Steg, Ph

AU - Gabriel Steg, P. H.

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 - Sinnaeve, Peter

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 - Clemmensen, Peter

AU - Bang, Lia E.

AU - Hove, Jens D.

AU - Gislason, Gunnar

AU - Larsen, John

AU - Johansen, Peter

AU - Jeppesen, Jørgen

AU - Nielsen, Peter Kaiser

AU - Hansen, Ole

AU - Jensen, Steen Agergaard

AU - Rosenberg, Michael

AU - Andersen, Dorthe

AU - ODYSSEY OUTCOMES Committees and Investigators

PY - 2021

Y1 - 2021

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. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

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. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

KW - acute coronary syndrome

KW - lipoprotein(a)

KW - low-density lipoprotein cholesterol

KW - PCSK9 inhibitor

U2 - 10.1016/j.jacc.2021.04.102

DO - 10.1016/j.jacc.2021.04.102

M3 - Journal article

C2 - 34325831

AN - SCOPUS:85110291084

VL - 78

SP - 421

EP - 433

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 5

ER -

ID: 301441210