Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk

ML. O'Donoghue, S. Fazio, RP. Giugliano, ESG. Stroes, E. Kanevsky, I. Gouni-Berthold, K. Im, A. Lira Pineda, SM. Wasserman, R. Češka, MV. Ezhov, JW. Jukema, HK. Jensen, SL. Tokgözoğlu, F. Mach, K. Huber, PS. Sever, AC. Keech, TR. Pedersen, MS. Sabatine,

. 2019 ; 139 (12) : 1483-1492. [pub] 20190319

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, randomizované kontrolované studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19045077

BACKGROUND: Lipoprotein(a) [Lp(a)] may play a causal role in atherosclerosis. PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors have been shown to significantly reduce plasma Lp(a) concentration. However, the relationship between Lp(a) levels, PCSK9 inhibition, and cardiovascular risk reduction remains undefined. METHODS: Lp(a) was measured in 25 096 patients in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a randomized trial of evolocumab versus placebo in patients with established atherosclerotic cardiovascular disease (median follow-up, 2.2 years). Cox models were used to assess the independent prognostic value of Lp(a) and the efficacy of evolocumab for coronary risk reduction by baseline Lp(a) concentration. RESULTS: The median (interquartile range) baseline Lp(a) concentration was 37 (13-165) nmol/L. In the placebo arm, patients with baseline Lp(a) in the highest quartile had a higher risk of coronary heart disease death, myocardial infarction, or urgent revascularization (adjusted hazard ratio quartile 4: quartile 1, 1.22; 95% CI, 1.01-1.48) independent of low-density lipoprotein cholesterol. At 48 weeks, evolocumab significantly reduced Lp(a) by a median (interquartile range) of 26.9% (6.2%-46.7%). The percent change in Lp(a) and low-density lipoprotein cholesterol at 48 weeks in patients taking evolocumab was moderately positively correlated ( r=0.37; 95% CI, 0.36-0.39; P<0.001). Evolocumab reduced the risk of coronary heart disease death, myocardial infarction, or urgent revascularization by 23% (hazard ratio, 0.77; 95% CI, 0.67-0.88) in patients with a baseline Lp(a) >median, and by 7% (hazard ratio, 0.93; 95% CI, 0.80-1.08; P interaction=0.07) in those ≤median. Coupled with the higher baseline risk, the absolute risk reductions, and number needed to treat over 3 years were 2.49% and 40 versus 0.95% and 105, respectively. CONCLUSIONS: Higher levels of Lp(a) are associated with an increased risk of cardiovascular events in patients with established cardiovascular disease irrespective of low-density lipoprotein cholesterol. Evolocumab significantly reduced Lp(a) levels, and patients with higher baseline Lp(a) levels experienced greater absolute reductions in Lp(a) and tended to derive greater coronary benefit from PCSK9 inhibition. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19045077
003      
CZ-PrNML
005      
20200113105746.0
007      
ta
008      
200109s2019 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1161/CIRCULATIONAHA.118.037184 $2 doi
035    __
$a (PubMed)30586750
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a O'Donoghue, Michelle L $u TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.L.O., R.P.G., E.K., K.A.I., M.S.S.).
245    10
$a Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk / $c ML. O'Donoghue, S. Fazio, RP. Giugliano, ESG. Stroes, E. Kanevsky, I. Gouni-Berthold, K. Im, A. Lira Pineda, SM. Wasserman, R. Češka, MV. Ezhov, JW. Jukema, HK. Jensen, SL. Tokgözoğlu, F. Mach, K. Huber, PS. Sever, AC. Keech, TR. Pedersen, MS. Sabatine,
520    9_
$a BACKGROUND: Lipoprotein(a) [Lp(a)] may play a causal role in atherosclerosis. PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors have been shown to significantly reduce plasma Lp(a) concentration. However, the relationship between Lp(a) levels, PCSK9 inhibition, and cardiovascular risk reduction remains undefined. METHODS: Lp(a) was measured in 25 096 patients in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a randomized trial of evolocumab versus placebo in patients with established atherosclerotic cardiovascular disease (median follow-up, 2.2 years). Cox models were used to assess the independent prognostic value of Lp(a) and the efficacy of evolocumab for coronary risk reduction by baseline Lp(a) concentration. RESULTS: The median (interquartile range) baseline Lp(a) concentration was 37 (13-165) nmol/L. In the placebo arm, patients with baseline Lp(a) in the highest quartile had a higher risk of coronary heart disease death, myocardial infarction, or urgent revascularization (adjusted hazard ratio quartile 4: quartile 1, 1.22; 95% CI, 1.01-1.48) independent of low-density lipoprotein cholesterol. At 48 weeks, evolocumab significantly reduced Lp(a) by a median (interquartile range) of 26.9% (6.2%-46.7%). The percent change in Lp(a) and low-density lipoprotein cholesterol at 48 weeks in patients taking evolocumab was moderately positively correlated ( r=0.37; 95% CI, 0.36-0.39; P<0.001). Evolocumab reduced the risk of coronary heart disease death, myocardial infarction, or urgent revascularization by 23% (hazard ratio, 0.77; 95% CI, 0.67-0.88) in patients with a baseline Lp(a) >median, and by 7% (hazard ratio, 0.93; 95% CI, 0.80-1.08; P interaction=0.07) in those ≤median. Coupled with the higher baseline risk, the absolute risk reductions, and number needed to treat over 3 years were 2.49% and 40 versus 0.95% and 105, respectively. CONCLUSIONS: Higher levels of Lp(a) are associated with an increased risk of cardiovascular events in patients with established cardiovascular disease irrespective of low-density lipoprotein cholesterol. Evolocumab significantly reduced Lp(a) levels, and patients with higher baseline Lp(a) levels experienced greater absolute reductions in Lp(a) and tended to derive greater coronary benefit from PCSK9 inhibition. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633.
650    _2
$a dospělí $7 D000328
650    _2
$a senioři $7 D000368
650    _2
$a senioři nad 80 let $7 D000369
650    _2
$a humanizované monoklonální protilátky $x terapeutické užití $7 D061067
650    _2
$a anticholesteremika $x terapeutické užití $7 D000924
650    _2
$a ateroskleróza $x farmakoterapie $x patologie $7 D050197
650    _2
$a LDL-cholesterol $x krev $7 D008078
650    _2
$a dvojitá slepá metoda $7 D004311
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a lidé $7 D006801
650    _2
$a lipoprotein (a) $x krev $7 D017270
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a placebo efekt $7 D015990
650    _2
$a proporcionální rizikové modely $7 D016016
650    _2
$a proproteinkonvertasa subtilisin/kexin typu 9 $x imunologie $x metabolismus $7 D000071449
650    _2
$a rizikové faktory $7 D012307
650    _2
$a výsledek terapie $7 D016896
655    _2
$a časopisecké články $7 D016428
655    _2
$a randomizované kontrolované studie $7 D016449
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Fazio, Sergio $u Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland (S.F.).
700    1_
$a Giugliano, Robert P $u TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.L.O., R.P.G., E.K., K.A.I., M.S.S.).
700    1_
$a Stroes, Erik S G $u Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands (E.S.G.S.).
700    1_
$a Kanevsky, Estella $u TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.L.O., R.P.G., E.K., K.A.I., M.S.S.).
700    1_
$a Gouni-Berthold, Ioanna $u Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany (I.G.-B.).
700    1_
$a Im, KyungAh $u TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.L.O., R.P.G., E.K., K.A.I., M.S.S.).
700    1_
$a Lira Pineda, Armando $u Amgen, Thousand Oaks, CA (A.L.P., S.M.W.).
700    1_
$a Wasserman, Scott M $u Amgen, Thousand Oaks, CA (A.L.P., S.M.W.).
700    1_
$a Češka, Richard $u Center for Preventive Cardiology, 3rd Internal Medicine Clinic, University General Hospital and Charles University 1st Medical Faculty, Prague, Czech Republic (R.C.).
700    1_
$a Ezhov, Marat V $u National Cardiology Research Center, Moscow, Russia (M.V.E.).
700    1_
$a Jukema, J Wouter $u Department of Cardiology, Leiden University Medical Center, The Netherlands (J.W.J.).
700    1_
$a Jensen, Henrik K $u Department of Cardiology, Aarhus University Hospital and Department of Clinical Medicine, Health, Aarhus University, Denmark (H.K.J.).
700    1_
$a Tokgözoğlu, S Lale $u Cardiovascular Division, Hacettepe University, Ankara, Turkey (S.L.T.).
700    1_
$a Mach, François $u Cardiology Division, University of Geneva, Switzerland (F.M.).
700    1_
$a Huber, Kurt $u 3rd Department of Medicine, Cardiology and Intensive Care Medicine, Wilhelminenhospital and Sigmund Freud University, Medical Faculty, Vienna, Austria (K.H.).
700    1_
$a Sever, Peter S $u Imperial College London, UK (P.S.S.).
700    1_
$a Keech, Anthony C $u Sydney Medical School, National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Australia (A.C.K.).
700    1_
$a Pedersen, Terje R $u Oslo University Hospital, Ullevål and Medical Faculty, University of Oslo, Norway (T.R.P.).
700    1_
$a Sabatine, Marc S $u TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.L.O., R.P.G., E.K., K.A.I., M.S.S.).
773    0_
$w MED00001091 $t Circulation $x 1524-4539 $g Roč. 139, č. 12 (2019), s. 1483-1492
856    41
$u https://pubmed.ncbi.nlm.nih.gov/30586750 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20200109 $b ABA008
991    __
$a 20200113110118 $b ABA008
999    __
$a ok $b bmc $g 1483346 $s 1083750
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2019 $b 139 $c 12 $d 1483-1492 $e 20190319 $i 1524-4539 $m Circulation (New York, N.Y.) $n Circulation (New York) $x MED00001091
LZP    __
$a Pubmed-20200109
Zpět

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace