SynthesisCirculation2017
Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies.
8 registry-linked trialsOpen access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in Circulation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01652703. Cited by 26 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 2 pooled it
11.9field-weighted citation impact, top 1% of its field
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.
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.
A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Stable Statin Therapy in Japanese Subjects With Hypercholesterolemia and High Cardiovascular Risk
Open the trial in the graphA Double-blind, Randomized, Placebo and Ezetimibe-controlled, Multicenter Study to Evaluate Safety and Efficacy of Lipid Lowering Monotherapy With AMG 145 in Subjects With a 10-Year Framingham Risk Score of 10% or Less
PMID 29353350PMID 29768954PMID 24691094PMID 29736889PMID 30120772PMID 30755061PMID 30852766PMID 32114889PMID 32564340PMID 33325247other papers from this trial
Open the trial in the graphA Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia
PMID 29353350PMID 29768954PMID 24825642PMID 24481874PMID 33325247PMID 32564340PMID 32114889PMID 30852766PMID 30755061PMID 30120772PMID 29736889other papers from this trial
Open the trial in the graphA Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of AMG 145, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor
PMID 29353350PMID 29768954PMID 30073585PMID 24694531PMID 24477778PMID 32564340PMID 32114889PMID 30755061PMID 30120772PMID 29736889other papers from this trial
Open the trial in the graphA Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Subjects With Heterozygous Familial Hypercholesterolemia
PMID 29353350PMID 29768954PMID 30755061PMID 25282519PMID 29736889PMID 30120772other papers from this trial
Open the trial in the graphA Multi-center, Randomized Study in Subjects With Primary Hypercholesterolemia or Mixed Dyslipidemia to Assess Subjects' Ability to Administer a Full Dose of Evolocumab (AMG 145) in Home-use, Using Either a Prefilled Syringe or a Prefilled Autoinjector/Pen
Open the trial in the graphA Multicenter, Randomized Study in Subjects With Primary Hypercholesterolemia or Mixed Dyslipidemia to Assess Subjects' Ability to Administer a Full Dose of Evolocumab (AMG 145) in Home-use, Using Either a 3.5 mL Personal Injector or a Prefilled Autoinjector/Pen.
Open the trial in the graphA Double-Blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Long-Term Tolerability and Durable Efficacy of AMG 145 (Evolocumab) on LDL-C in Hyperlipidemic Subjects
Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Anti-PCSK9 antibodies for hypercholesterolaemia: Overview of clinical data and implications for primary care.International journal of clinical practice · 2017Pooled it
- Lipid-lowering Drugs and Neurocognitive Function: A Systematic Review.In vivo (Athens, Greece)Pooled it
- Randomized study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Pre-specified analysis of the Chinese population from the BERSON clinical trial.Diabetes, obesity & metabolism · 2019Trial
- Evolocumab-Induced Angioedema: First Documented Case and Review of a Rare Adverse Event.JACC. Case reports · 2026Article
- Pharmacological considerations for next-generation protein therapeutics in cardiovascular disease.The Journal of pharmacology and experimental therapeutics · 2025Review
- Association between lipid-lowering agents with intervertebral disc degeneration, sciatica and low back pain: a drug-targeted mendelian randomized study and cross-sectional observation.Lipids in health and disease · 2024Observational
- PCSK9 Inhibitors and Infection-Related Adverse Events: A Pharmacovigilance Study Using the World Health Organization VigiBase.Drugs - real world outcomes · 2024Article
- LDL-C rebound after long-term evolocumab treatment and intravascular imaging evidence in a familial hypercholesterolemia patient with early-onset myocardial infarction.Chronic diseases and translational medicine · 2024Article
- Real-World Insights into Evolocumab Use in Patients with Hyperlipidemia Across Five Countries: Analysis from the ZERBINI Study.Cardiology and therapy · 2023Article
- The Effect of PCSK9 Inhibition on the Stabilization of Atherosclerotic Plaque Determined by Biochemical and Diagnostic Imaging Methods.Molecules (Basel, Switzerland) · 2023Article
- PCSK-9 inhibitors: a new direction for the future treatment of ischemic stroke.Frontiers in pharmacology · 2023Review
- Real-World Insights Into Evolocumab Use in Patients With Hyperlipidemia: Canadian Analysis From the ZERBINI Study.CJC open · 2022Article
- Musculoskeletal Adverse Events Associated with PCSK9 Inhibitors: Disproportionality Analysis of the FDA Adverse Event Reporting System.Cardiovascular therapeutics · 2022Article
- The Aggressive Diabetic Kidney Disease in Youth-Onset Type 2 Diabetes: Pathogenetic Mechanisms and Potential Therapies.Medicina (Kaunas, Lithuania) · 2021Review
- Proprotein convertase subtilisin/kexin type 9 inhibition in cardiovascular disease: current status and future perspectives.The Korean journal of internal medicine · 2020Review
- New Perspectives on Atherogenic Dyslipidaemia and Cardiovascular Disease.European cardiology · 2020Review
- Effect of Access to Prescribed PCSK9 Inhibitors on Cardiovascular Outcomes.Circulation. Cardiovascular quality and outcomes · 2019Article
- Novel strategies to target proprotein convertase subtilisin kexin 9: beyond monoclonal antibodies.Cardiovascular research · 2019Review
- Adverse Events Associated With PCSK9 Inhibitors: A Real-World Experience.Clinical pharmacology and therapeutics · 2019Article
- Validity of a Novel Method for Estimating Low-Density Lipoprotein Cholesterol Levels in Cardiovascular Disease Patients Treated with Statins.Journal of atherosclerosis and thrombosis · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 3 countries.
Peter P TothFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.). peter.toth@cghmc.com.
Olivier DescampsFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
Jacques GenestFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
Naveed SattarFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
David PreissFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
Ricardo DentFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
Constantine DjedjosFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
Yuna WuFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
Michelle GellerFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
Magdalena UhartFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
Ransi SomaratneFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
Scott M WassermanFrom CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).
PROFICIO Investigators
McGill University Health Centre · CAUniversity of Oxford · GBMedical Research Council · GBMRC Population Health Research UnitUniversity of Glasgow · GB
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEvolocumab, a fully human monoclonal antibody to PCSK9 (proprotein convertase subtilisin/kexin type 9), markedly reduces low-density lipoprotein cholesterol across diverse patient populations. The objective of this study was to assess the safety and tolerability of evolocumab in a pooled safety analysis from phase 2 or 3 randomized and placebo or comparator-controlled trials (integrated parent trials) and the first year of open-label extension (OLE) trials that included a standard-of-care control group.
methodsThis analysis included adverse event (AE) data from 6026 patients in 12 phase 2 and 3 parent trials, with a median exposure of 2.8 months, and, of those patients, from 4465 patients who continued with a median follow-up of 11.1 months in 2 OLE trials. AEs were analyzed separately for the parent and OLE trials. Overall AE rates, serious AEs, laboratory assessments, and AEs of interest were evaluated.
resultsOverall AE rates were similar between evolocumab and control in the parent trials (51.1% versus 49.6%) and in year 1 of OLE trials (70.0% versus 66.0%), as were those for serious AEs. Elevations of serum transaminases, bilirubin, and creatine kinase were infrequent and similar between groups. Muscle-related AEs were similar between evolocumab and control. Neurocognitive AEs were infrequent and balanced during the double-blind parent studies (5 events [0.1%], evolocumab groups versus 6 events [0.3%], control groups). In the OLE trials, 27 patients (0.9%) in the evolocumab groups and 5 patients (0.3%) in the control groups reported neurocognitive AEs. No neutralizing antievolocumab antibodies were detected.
conclusionsOverall, this integrated safety analysis of 6026 patients pooled across phase 2/3 trials and 4465 patients who continued in OLE trials for 1 year supports a favorable benefit-risk profile for evolocumab.
Indexed as
Clinical Trials, Phase II as TopicClinical Trials, Phase III as TopicAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedDouble-Blind MethodHumansMuscular DiseasesAntibodies, MonoclonalAntibodies, Monoclonal, Humanizedevolocumabantibodies monoclonalcholesterol, LDLlong-term adverse eventsmyalgiaproprotein convertase 9
Identifiers
What Socratic holds
Textmetadata
Read underepoch 390
Registered trials
NCT01652703ClinicalTrials.gov
NCT01763827ClinicalTrials.gov
NCT01763866ClinicalTrials.gov
NCT01763905ClinicalTrials.gov
NCT01763918ClinicalTrials.gov
NCT01849497ClinicalTrials.gov
and 2 more above
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.