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Article: Effect of Alirocumab on Stroke in ODYSSEY OUTCOMES

TitleEffect of Alirocumab on Stroke in ODYSSEY OUTCOMES
Authors
KeywordsAcute coronary syndrome
Cerebrovascular disorders
Lipoprotein, LDL
Stroke
Issue Date2019
PublisherAmerican Heart Association. The Journal's web site is located at http://circ.ahajournals.org
Citation
Circulation, 2019, v. 140 n. 25, p. 2054-2062 How to Cite?
AbstractBackground: Lowering of atherogenic lipoproteins, including low-density lipoprotein cholesterol (LDL-C), reduces the risk of ischemic stroke. However, concerns have been raised about very low LDL-C levels and a potential increased risk of hemorrhagic stroke. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, despite intensive statin therapy, targeting LDL-C levels of 25 to 50 mg/dL and avoiding sustained LDL-C <15 mg/dL. This prespecified analysis was designed to assess the effect of alirocumab on ischemic and hemorrhagic stroke. We hypothesized that for patients treated with alirocumab there would be a reduction in risk of ischemic stroke without increasing hemorrhagic stroke, irrespective of baseline LDL-C and of history of cerebrovascular disease. Methods: Patients were randomized to alirocumab or placebo 1 to 12 months after acute coronary syndrome. The risk of nonfatal or fatal ischemic or hemorrhagic stroke was evaluated, stratified by baseline LDL-C concentration and history of cerebrovascular disease. A potential association of very low achieved LDL-C with alirocumab treatment at month 4 and subsequent hemorrhagic stroke was assessed. Results: Median follow-up was 2.8 years. In total, 263 ischemic and 33 hemorrhagic strokes occurred. Alirocumab reduced the risk of any stroke (HR, 0.72 [95% CI, 0.57−0.91]) and ischemic stroke (HR, 0.73 [95% CI, 0.57−0.93]) without increasing hemorrhagic stroke (HR, 0.83 [95% CI, 0.42−1.65]). In total, 7164 (37.9%), 6128 (32.4%), and 5629 (29.7%) patients had a baseline LDL-C of <80, 80 to 100, and >100 mg/dL, respectively. The treatment effect on stroke appeared numerically greater for patients with higher baseline LDL-C, but there was no formal evidence of heterogeneity (Pinteraction=0.31). The effect of alirocumab on stroke was similar among 944 patients (5.0%) with a history of previous cerebrovascular disease and among those without a history of cerebrovascular disease (Pinteraction=0.37). There was no apparent adverse relation between lower achieved LDL-C and incidence of hemorrhagic stroke in the alirocumab group. Conclusions: In patients with recent acute coronary syndrome and dyslipidemia despite intensive statin therapy, alirocumab decreased the risk of stroke, irrespective of baseline LDL-C and history of cerebrovascular disease, over a median follow-up of 2.8 years. Furthermore, risk of hemorrhagic stroke did not depend on achieved LDL-C levels within the alirocumab group. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402.
Persistent Identifierhttp://hdl.handle.net/10722/287280
ISSN
2020 Impact Factor: 29.69
2015 SCImago Journal Rankings: 7.853
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJukema, JW-
dc.contributor.authorZijlstra, LE-
dc.contributor.authorBhatt, DL-
dc.contributor.authorBittner, VA-
dc.contributor.authorDiaz, R-
dc.contributor.authorDrexel, H-
dc.contributor.authorGoodman, SG-
dc.contributor.authorKim, YU-
dc.contributor.authorPordy, R-
dc.contributor.authorReiner, Ž-
dc.contributor.authorRoe, MT-
dc.contributor.authorTse, HF-
dc.contributor.authorValdovinos, PCM-
dc.contributor.authorWhite, HD-
dc.contributor.authorZeiher, AM-
dc.contributor.authorSzarek, M-
dc.contributor.authorSchwart, GG-
dc.contributor.authorSteg, PG-
dc.contributor.authorFor the ODYSSEY OUTCOMES Investigators-
dc.date.accessioned2020-09-22T02:58:35Z-
dc.date.available2020-09-22T02:58:35Z-
dc.date.issued2019-
dc.identifier.citationCirculation, 2019, v. 140 n. 25, p. 2054-2062-
dc.identifier.issn0009-7322-
dc.identifier.urihttp://hdl.handle.net/10722/287280-
dc.description.abstractBackground: Lowering of atherogenic lipoproteins, including low-density lipoprotein cholesterol (LDL-C), reduces the risk of ischemic stroke. However, concerns have been raised about very low LDL-C levels and a potential increased risk of hemorrhagic stroke. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, despite intensive statin therapy, targeting LDL-C levels of 25 to 50 mg/dL and avoiding sustained LDL-C <15 mg/dL. This prespecified analysis was designed to assess the effect of alirocumab on ischemic and hemorrhagic stroke. We hypothesized that for patients treated with alirocumab there would be a reduction in risk of ischemic stroke without increasing hemorrhagic stroke, irrespective of baseline LDL-C and of history of cerebrovascular disease. Methods: Patients were randomized to alirocumab or placebo 1 to 12 months after acute coronary syndrome. The risk of nonfatal or fatal ischemic or hemorrhagic stroke was evaluated, stratified by baseline LDL-C concentration and history of cerebrovascular disease. A potential association of very low achieved LDL-C with alirocumab treatment at month 4 and subsequent hemorrhagic stroke was assessed. Results: Median follow-up was 2.8 years. In total, 263 ischemic and 33 hemorrhagic strokes occurred. Alirocumab reduced the risk of any stroke (HR, 0.72 [95% CI, 0.57−0.91]) and ischemic stroke (HR, 0.73 [95% CI, 0.57−0.93]) without increasing hemorrhagic stroke (HR, 0.83 [95% CI, 0.42−1.65]). In total, 7164 (37.9%), 6128 (32.4%), and 5629 (29.7%) patients had a baseline LDL-C of <80, 80 to 100, and >100 mg/dL, respectively. The treatment effect on stroke appeared numerically greater for patients with higher baseline LDL-C, but there was no formal evidence of heterogeneity (Pinteraction=0.31). The effect of alirocumab on stroke was similar among 944 patients (5.0%) with a history of previous cerebrovascular disease and among those without a history of cerebrovascular disease (Pinteraction=0.37). There was no apparent adverse relation between lower achieved LDL-C and incidence of hemorrhagic stroke in the alirocumab group. Conclusions: In patients with recent acute coronary syndrome and dyslipidemia despite intensive statin therapy, alirocumab decreased the risk of stroke, irrespective of baseline LDL-C and history of cerebrovascular disease, over a median follow-up of 2.8 years. Furthermore, risk of hemorrhagic stroke did not depend on achieved LDL-C levels within the alirocumab group. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402.-
dc.languageeng-
dc.publisherAmerican Heart Association. The Journal's web site is located at http://circ.ahajournals.org-
dc.relation.ispartofCirculation-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAcute coronary syndrome-
dc.subjectCerebrovascular disorders-
dc.subjectLipoprotein, LDL-
dc.subjectStroke-
dc.titleEffect of Alirocumab on Stroke in ODYSSEY OUTCOMES-
dc.typeArticle-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.authorityTse, HF=rp00428-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1161/CIRCULATIONAHA.119.043826-
dc.identifier.pmid31707788-
dc.identifier.pmcidPMC6919220-
dc.identifier.scopuseid_2-s2.0-85076872837-
dc.identifier.hkuros314406-
dc.identifier.volume140-
dc.identifier.issue25-
dc.identifier.spage2054-
dc.identifier.epage2062-
dc.identifier.isiWOS:000508228600121-
dc.publisher.placeUnited States-
dc.identifier.issnl0009-7322-

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