Evidence map›Paper›PMID 29186504›Full record

SynthesisEuropean heart journal2018

No evidence of neurocognitive adverse events associated with alirocumab treatment in 3340 patients from 14 randomized Phase 2 and 3 controlled trials: a meta-analysis of individual patient data.

Philip D Harvey, Marwan N Sabbagh, John E Harrison, Henry N Ginsberg, M John Chapman, Garen Manvelian, Angele Moryusef, Jonas Mandel, Michel Farnier

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in European heart journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 4 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Guideline
  3. Pooled it
  4. Biotechnology Approaches for the Treatment of Dyslipidemia.Cardiovascular drugs and therapy · 2021
    Pooled it
  5. Trial
  6. Review
  7. Review
  8. Review
  9. Review
  10. PCSK9 Monoclonal Antibodies Have Come a Long Way.Current atherosclerosis reports · 2024
    Review
  11. Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation.European heart journal. Cardiovascular pharmacotherapy · 2024
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Philip D HarveyDepartment of Psychiatry, University of Miami Miller School of Medicine, 1120 NW 14th Street, Suite 1450, Miami, FL, USA.
Marwan N SabbaghBarrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.
John E HarrisonAlzheimer Center, VUmc, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands.
Henry N GinsbergColumbia University, 622 West 168 Street, New York, NY 10032, USA.
M John ChapmanUniversity of Pierre and Marie Curie, 47-83 Boulevard de l'Hôpital, 75013 Paris, France.
Garen ManvelianRegeneron Pharmaceuticals, 777 Old Saw River Road, Tarrytown, NY 10591, USA.
Angele MoryusefSanofi, 55 Corporate Drive, Bridgewater, NJ 08807, USA.
Jonas MandelSanofi, 1 Avenue Pierre Brossolette, 91380 Chilly-Mazarin, France, and IviData Stats, 79 Baudin Street, 92300 Levallois-Perret, France.
Michel FarnierPoint Médical, Rond Point de la Nation, 21000 Dijon, France, and Department of Cardiology, CHU Dijon Bourgogne, 2 Bd Maréchal de Lattre of Tassigny, 21000 Dijon, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aims: Despite patient reports of neurocognitive disorders with lipid-lowering treatments (LLTs), large clinical trials have found no significant association between neurocognitive disorders and LLTs. We assessed incidence of neurocognitive treatment-emergent adverse events (TEAEs) from 14 Phase 2 and 3 trials of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab. Methods and results: Patients (most on background maximally tolerated statin) received alirocumab 75/150 mg every 2 weeks (n = 3340; 4029 patient-years of exposure), placebo (n = 1276), or ezetimibe (n = 618). Data were pooled by the control used. Neurocognitive TEAEs were reported by 22 (0.9%) alirocumab-treated patients vs. 9 (0.7%) with placebo in placebo-controlled trials [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.57-2.68] and 10 (1.2%) with alirocumab vs. 8 (1.3%) with ezetimibe in ezetimibe-controlled trials (HR 0.81, 95% CI 0.32-2.08). Rates of neurocognitive TEAEs were similar in patients receiving alirocumab with LDL cholesterol (LDL-C) levels <25 mg/dL (<0.65 mmol/L; n = 5/839; 0.6%; 0.5/100 patient-years) vs. ≥25 mg/dL (n = 26/2501; 1.0%; 0.8/100 patient-years). One patient (0.1%; ezetimibe-controlled pool) receiving alirocumab had a neurocognitive TEAE leading to discontinuation vs. two (0.2%) patients receiving placebo and three (0.4%) patients receiving ezetimibe. Neurocognitive TEAE incidence was also similar between alirocumab and controls when stratified by age. Conclusions: Neurocognitive TEAE incidences were low (≤1.2%), with no significant differences between alirocumab vs. controls up to 104 weeks. No association was found between neurocognitive TEAEs and LDL-C <25 mg/dL based on the completed Phase 2 and 3 trials examined, although long-term effects of very low LDL-C levels induced by PCSK9 inhibitors are currently unknown.

Indexed as

Nervous System DiseasesAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAnticholesteremic AgentsCognitionDrug-Related Side Effects and Adverse ReactionsFemaleHumansMaleMiddle AgedRandomized Controlled Trials as TopicalirocumabAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAnticholesteremic AgentsCholesterol-lowering drugsCognitive functionLDLPatient safetyPCSK9

Identifiers

PMID29186504
PMCPMC5837381

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.