Evidence map›Paper›PMID 26757788›Full record

Trial reportEuropean heart journal2016

Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): a randomized, placebo-controlled Phase 2 study.

John J P Kastelein, Steven E Nissen, Daniel J Rader, G Kees Hovingh, Ming-Dauh Wang, Tong Shen, Kathryn A Krueger

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European heart journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 5 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

24 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Review
  8. Naturally Occurring PCSK9 Inhibitors: An Updated Review.Molecules (Basel, Switzerland) · 2025
    Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Effects of Cardiovascular Risk Factor Variability on Health Outcomes.Endocrinology and metabolism (Seoul, Korea) · 2020
    Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

John J P KasteleinDepartment of Vascular Medicine, Academic Medical Center of the University of Amsterdam, Meibergdreef 9, Room F4-159.2, 1105 AZ Amsterdam, The Netherlands J.J.Kastelein@amc.uva.nl juliesherman@lilly.com.
Steven E NissenCleveland Clinic Heart and Vascular Institute, Cleveland, OH, USA.
Daniel J RaderUniversity of Pennsylvania, Philadelphia, PA, USA.
G Kees HovinghDepartment of Vascular Medicine, Academic Medical Center of the University of Amsterdam, Meibergdreef 9, Room F4-159.2, 1105 AZ Amsterdam, The Netherlands.
Ming-Dauh WangEli Lilly and Company, Indianapolis, IN, USA.
Tong ShenEli Lilly and Company, Indianapolis, IN, USA.
Kathryn A KruegerEli Lilly and Company, Indianapolis, IN, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThe objective of this study was to evaluate the efficacy, safety, and tolerability of LY3015014 (LY), a neutralizing antibody of proprotein convertase subtilisin/kexin type 9 (PCSK9), administered every 4 or 8 weeks in patients with primary hypercholesterolaemia, when added to a background of standard-of-care lipid-lowering therapy, including statins. METHODS AND

resultsDouble-blind, placebo-controlled trial randomized 527 patients with primary hypercholesterolaemia from June 2013 to January 2014 at 61 community and academic centres in North America, Europe, and Japan. Patients were randomized to subcutaneous injections of LY 20, 120, or 300 mg every 4 weeks (Q4W); 100 or 300 mg every 8 weeks (Q8W) alternating with placebo Q4W; or placebo Q4W. The primary endpoint was percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) by beta quantification at Week 16. The mean baseline LDL-C by beta quantification was 136.3 (SD, 45.0)mg/dL. LY3015014 dose-dependently decreased LDL-C, with a maximal reduction of 50.5% with 300 mg LY Q4W and 37.1% with 300 mg LY Q8W compared with a 7.6% increase with placebo maintained at the end of the dosing interval. There were no treatment-related serious adverse events (AEs). The most common AE terms (>10% of any treatment group) reported more frequently with LY compared with placebo were injection site (IS) pain and IS erythema. No liver or muscle safety issues emerged.

conclusionsLY3015014 dosed every 4 or 8 weeks, resulted in robust and durable reductions in LDL-C. No clinically relevant safety issues emerged with the administration of LY. The long-term effects on cardiovascular outcomes require further investigation.

Indexed as

Antibodies, MonoclonalAnticholesteremic AgentsCholesterol, LDLDouble-Blind MethodEuropeHumansJapanProprotein Convertase 9Proprotein ConvertasesSerine EndopeptidasesSubtilisinsTreatment OutcomeAntibodies, MonoclonalAnticholesteremic AgentsCholesterol, LDLfrovocimabPCSK9 protein, humanProprotein Convertase 9Proprotein ConvertasesSerine EndopeptidasesSubtilisinsHypercholesterolaemiaLipid-lowering therapyLow-density lipoprotein cholesterol

Identifiers

PMID26757788
PMCPMC4852062

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Registered trials

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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.