Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk: Insights from the FOURIER Trial

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F19%3A10389049" target="_blank" >RIV/00064165:_____/19:10389049 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/19:10389049

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ncvLBlwyDh" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ncvLBlwyDh</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1161/CIRCULATIONAHA.118.037184" target="_blank" >10.1161/CIRCULATIONAHA.118.037184</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk: Insights from the FOURIER Trial

Popis výsledku v původním jazyce

Background: Lipoprotein(a) [Lp(a)] may play a causal role in atherosclerosis. Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors have been shown to significantly reduce plasma Lp(a) concentration. However, the relationship between Lp(a) levels, PCSK9 inhibition and cardiovascular (CV) risk reduction remains undefined. Methods: Lp(a) was measured in 25,096 patients in FOURIER, a randomized trial of evolocumab versus placebo in patients with established atherosclerotic CV 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 [IQR] 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 (CHD) death, MI or urgent revascularization (UR) (adjusted HR Q4:Q1 1.22, 95% CI 1.01-1.48) independent of LDL-C. At 48 weeks, evolocumab significantly reduced Lp(a) by a median [IQR] of 26.9% [6.2-46.7%]. The percent change in Lp(a) and LDL-C at 48 weeks in evolocumab patients was moderately positively correlated (r=0.37, 95% CI 0.36-0.39, P&lt;0.001). Evolocumab reduced the risk of CHD death, MI or UR by 23% (HR 0.77, 95% CI 0.67-0.88) in patients with a baseline Lp(a) &gt;median, and by 7% (HR 0.93, 0.80-1.08; P interaction=0.07) in those LESS-THAN OR EQUAL TOmedian. Coupled with the higher baseline risk, the absolute risk reductions and NNT3y were 2.49% and 40 vs. 0.95% and 105, respectively. Conclusions: Lp(a) is associated with the risk of CV events in patients with established CV disease irrespective of LDL-C. 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://clinicaltrials.gov Unique Identifier: NCT01764633.

Název v anglickém jazyce

Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk: Insights from the FOURIER Trial

Popis výsledku anglicky

Background: Lipoprotein(a) [Lp(a)] may play a causal role in atherosclerosis. Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors have been shown to significantly reduce plasma Lp(a) concentration. However, the relationship between Lp(a) levels, PCSK9 inhibition and cardiovascular (CV) risk reduction remains undefined. Methods: Lp(a) was measured in 25,096 patients in FOURIER, a randomized trial of evolocumab versus placebo in patients with established atherosclerotic CV 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 [IQR] 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 (CHD) death, MI or urgent revascularization (UR) (adjusted HR Q4:Q1 1.22, 95% CI 1.01-1.48) independent of LDL-C. At 48 weeks, evolocumab significantly reduced Lp(a) by a median [IQR] of 26.9% [6.2-46.7%]. The percent change in Lp(a) and LDL-C at 48 weeks in evolocumab patients was moderately positively correlated (r=0.37, 95% CI 0.36-0.39, P&lt;0.001). Evolocumab reduced the risk of CHD death, MI or UR by 23% (HR 0.77, 95% CI 0.67-0.88) in patients with a baseline Lp(a) &gt;median, and by 7% (HR 0.93, 0.80-1.08; P interaction=0.07) in those LESS-THAN OR EQUAL TOmedian. Coupled with the higher baseline risk, the absolute risk reductions and NNT3y were 2.49% and 40 vs. 0.95% and 105, respectively. Conclusions: Lp(a) is associated with the risk of CV events in patients with established CV disease irrespective of LDL-C. 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://clinicaltrials.gov Unique Identifier: NCT01764633.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Circulation

ISSN

0009-7322

e-ISSN

—

Svazek periodika

139

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

1483-1492

Kód UT WoS článku

000469318300005

EID výsledku v databázi Scopus

2-s2.0-85061789282