Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome Role of Lipoprotein(a) and Modification by Alirocumab: Prespecified Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10422993" target="_blank" >RIV/00216208:11130/20:10422993 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/20:10422993

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Oi3bS0WnZ0" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Oi3bS0WnZ0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046524" target="_blank" >10.1161/CIRCULATIONAHA.120.046524</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome Role of Lipoprotein(a) and Modification by Alirocumab: Prespecified Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Popis výsledku v původním jazyce

Background: Patients with acute coronary syndrome are at risk for peripheral artery disease (PAD) events and venous thromboembolism (VTE). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors reduce lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C) levels. Our objective was to ascertain whether PCSK9 inhibition reduces the risk of PAD events or VTE after acute coronary syndrome, and if such effects are related to levels of lipoprotein(a) or LDL-C. Methods: This was a prespecified analysis of the ODYSSEY OUTCOMES randomized clinical trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome), which was conducted in 18 924 patients with recent acute coronary syndrome on intensive or maximum-tolerated statin treatment who were randomized to the PCSK9 inhibitor alirocumab or placebo. In a prespecified analysis, PAD events (critical limb ischemia, limb revascularization, or amputation for ischemia) and VTE (deep vein thrombosis or pulmonary embolism) were assessed. LDL-C was corrected (LDL-C-corrected) for cholesterol content in lipoprotein(a). Results: At baseline, median lipoprotein(a) and LDL-C-corrected were 21 and 75 mg/dL, respectively; with alirocumab, median relative reductions were 23.5% and 70.6%, respectively. PAD events and VTE occurred in 246 and 92 patients, respectively. In the placebo group, risk of PAD events was related to baseline quartile of lipoprotein(a) (P-trend=0.0021), and tended to associate with baseline quartile of LDL-C-corrected (P-trend=0.06); VTE tended to associate with baseline quartile of lipoprotein(a) (P-trend=0.06), but not LDL-C-corrected (P-trend=0.85). Alirocumab reduced risk of PAD events (hazard ratio [HR], 0.69 [95% CI, 0.54-0.89]; P=0.004), with nonsignificantly fewer VTE events (HR, 0.67 [95% CI, 0.44-1.01]; P=0.06). Reduction in PAD events with alirocumab was associated with baseline quartile of lipoprotein(a) (P-trend=0.03), but not LDL-C-corrected (P-trend=0.50). With alirocumab, the change from baseline to Month 4 in lipoprotein(a), but not LDL-C-corrected, was associated with the risk of VTE and the composite of VTE and PAD events. Conclusions: In statin-treated patients with recent acute coronary syndrome, risk of PAD events is related to lipoprotein(a) level and is reduced by alirocumab, particularly among those with high lipoprotein(a). Further study is required to confirm whether risk of VTE is related to lipoprotein(a) level and its reduction with alirocumab. Registration: URL: ; Unique identifier: NCT01663402.

Název v anglickém jazyce

Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome Role of Lipoprotein(a) and Modification by Alirocumab: Prespecified Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Popis výsledku anglicky

Background: Patients with acute coronary syndrome are at risk for peripheral artery disease (PAD) events and venous thromboembolism (VTE). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors reduce lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C) levels. Our objective was to ascertain whether PCSK9 inhibition reduces the risk of PAD events or VTE after acute coronary syndrome, and if such effects are related to levels of lipoprotein(a) or LDL-C. Methods: This was a prespecified analysis of the ODYSSEY OUTCOMES randomized clinical trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome), which was conducted in 18 924 patients with recent acute coronary syndrome on intensive or maximum-tolerated statin treatment who were randomized to the PCSK9 inhibitor alirocumab or placebo. In a prespecified analysis, PAD events (critical limb ischemia, limb revascularization, or amputation for ischemia) and VTE (deep vein thrombosis or pulmonary embolism) were assessed. LDL-C was corrected (LDL-C-corrected) for cholesterol content in lipoprotein(a). Results: At baseline, median lipoprotein(a) and LDL-C-corrected were 21 and 75 mg/dL, respectively; with alirocumab, median relative reductions were 23.5% and 70.6%, respectively. PAD events and VTE occurred in 246 and 92 patients, respectively. In the placebo group, risk of PAD events was related to baseline quartile of lipoprotein(a) (P-trend=0.0021), and tended to associate with baseline quartile of LDL-C-corrected (P-trend=0.06); VTE tended to associate with baseline quartile of lipoprotein(a) (P-trend=0.06), but not LDL-C-corrected (P-trend=0.85). Alirocumab reduced risk of PAD events (hazard ratio [HR], 0.69 [95% CI, 0.54-0.89]; P=0.004), with nonsignificantly fewer VTE events (HR, 0.67 [95% CI, 0.44-1.01]; P=0.06). Reduction in PAD events with alirocumab was associated with baseline quartile of lipoprotein(a) (P-trend=0.03), but not LDL-C-corrected (P-trend=0.50). With alirocumab, the change from baseline to Month 4 in lipoprotein(a), but not LDL-C-corrected, was associated with the risk of VTE and the composite of VTE and PAD events. Conclusions: In statin-treated patients with recent acute coronary syndrome, risk of PAD events is related to lipoprotein(a) level and is reduced by alirocumab, particularly among those with high lipoprotein(a). Further study is required to confirm whether risk of VTE is related to lipoprotein(a) level and its reduction with alirocumab. Registration: URL: ; Unique identifier: NCT01663402.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

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

141

Číslo periodika v rámci svazku

20

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

1608-1617

Kód UT WoS článku

000536791300008

EID výsledku v databázi Scopus

2-s2.0-85084898110