Evidence map›Paper›PMID 31707788›Full record

Trial reportCirculation2019

Effect of Alirocumab on Stroke in ODYSSEY OUTCOMES.

J Wouter Jukema, Laurien E Zijlstra, Deepak L Bhatt, Vera A Bittner, Rafael Diaz, Heinz Drexel, Shaun G Goodman, Yong-Un Kim, Robert Pordy, Željko Reiner and 9 more

2 registry-linked trialsAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01663402. Cited by 62 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 6 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01663402 phase3completed

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Effect of Alirocumab (SAR236553/REGN727) on the Occurrence of Cardiovascular Events in Patients Who Have Recently Experienced an Acute Coronary Syndrome

Ran2012Enrolled18,924Registered outcomes15Posted comparisons6ConditionsAtherosclerotic Cardiovascular DiseaseArmsAlirocumab, LMT, Placebo
Open the trial in the graph
NCT07466251 phase4not yet recruitingnot on this mapstarted 2026, after this paper: background citation

PCSK9 Inhibitor for Intracranial Atherosclerosis Related Acute Ischemic Stroke (PISTIAS-3): a Randomized, Double-blind, Placebo-controlled Trial

TypeinterventionalSponsorPeking Union Medical College HospitalRan2026 to 2029Enrolled1,212ConditionsAcute Ischemic Stroke AIS, Intracranial Atherosclerosis ICAS, Atherosclerotic PlaqueArmsRecaticimab plus standard therapy, Recaticimab's placebo in combination with standard therapy
3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 6 syntheses or guidelines pooled it.

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  5. Biotechnology Approaches for the Treatment of Dyslipidemia.Cardiovascular drugs and therapy · 2021
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, The Netherlands (J.W.J., L.E.Z.).
Laurien E ZijlstraDepartment of Cardiology, Leiden University Medical Center, The Netherlands (J.W.J., L.E.Z.).
Deepak L BhattBrigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts (D.L.B.).
Vera A BittnerDivision of Cardiovascular Disease, University of Alabama at Birmingham (V.A.B.).
Rafael DiazEstudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Rosario, Argentina (R.D.).
Heinz DrexelLandeskrankenhaus Feldkirch, Austria (H.D.).
Shaun G GoodmanCanadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.).
Yong-Un KimSanofi, Paris, France (Y-U.K.).
Robert PordyRegeneron Pharmaceuticals Inc., Tarrytown, New York (R.P.).
Željko ReinerUniversity Hospital Center Zagreb, School of Medicine, University of Zagreb, Croatia (Z.R.).
Matthew T RoeDuke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina (M.T.R.).
Hung-Fat TseQueen Mary Hospital, The University of Hong Kong (H-F.T.).
Pablo Carlos Montenegro ValdovinosUnidad de Diagnostico Cardiologico, Guatemala City, Guatemala (P.C.M.V.).
Harvey D WhiteGreen Lane Cardiovascular Services, Auckland City Hospital, Auckland, New Zealand (H.D.W.).
Andreas M ZeiherDepartment of Medicine III, Goethe University, Frankfurt am Main, Germany (A.M.Z.).
Michael SzarekState University of New York, Downstate School of Public Health, Brooklyn (M.S.).
Gregory G SchwartzDivision of Cardiology, University of Colorado School of Medicine, Aurora (G.G.S.).
Philippe Gabriel StegAssistance Publique-Hôpitaux de Paris, Hôpital Bichat, Université de Paris, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris (P.G.S.).
ODYSSEY OUTCOMES Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLowering 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.

methodsPatients 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.

resultsMedian 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 (

conclusionsIn 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 registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402.

Indexed as

PCSK9 InhibitorsAgedAntibodies, Monoclonal, HumanizedFemaleFollow-Up StudiesHumansHypercholesterolemiaMaleMiddle AgedProprotein Convertase 9StrokeTreatment OutcomealirocumabAntibodies, Monoclonal, HumanizedPCSK9 InhibitorsPCSK9 protein, humanProprotein Convertase 9acute coronary syndromecerebrovascular disorderslipoprotein, LDLstroke

Identifiers

PMID31707788
PMCPMC6919220

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.