Evidence map›Paper›PMID 32219359›Full record

Trial reportJAMA2020

Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes: A Randomized Clinical Trial.

Kausik K Ray, Stephen J Nicholls, Kevin A Buhr, Henry N Ginsberg, Jan O Johansson, Kamyar Kalantar-Zadeh, Ewelina Kulikowski, Peter P Toth, Norman Wong, Michael Sweeney and 2 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in JAMA, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02586155. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
15.0field-weighted citation impact, top 1% of its field
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.

NCT02586155 phase3completed

A Phase III Multi-Center, Double-Blind, Randomized, Parallel Group, Placebo-Controlled Clinical Trial in High-Risk Type 2 Diabetes Mellitus (T2DM) Subjects With Coronary Artery Disease (CAD) to Determine Whether Bromodomain Extraterminal Domain (BET) Inhibition Treatment With RVX000222 Increases the Time to Major Adverse Cardiovascular Events (MACE)

Ran2015Enrolled2,425Registered outcomes14Posted comparisons5ConditionsCoronary Artery Disease, Diabetes Mellitus, Type 2ArmsApabetalone, Atorvastatin, Placebo, Rosuvastatin
Open the trial in the graph
3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.

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28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 8 institutions in 4 countries.

Kausik K RayImperial Centre for Cardiovascular Disease Prevention, Imperial College London, United Kingdom.
Stephen J NichollsMonash Cardiovascular Research Centre, Monash University, Melbourne, Victoria, Australia.
Kevin A BuhrStatistical Data Analysis Center, University of Wisconsin-Madison.
Henry N GinsbergIrving Institute for Clinical and Translational Research, Columbia University, New York, New York.
Jan O JohanssonResverlogix Corporation, Calgary, Alberta, Canada.
Kamyar Kalantar-ZadehDivision of Nephrology and Hypertension, University of California-Irvine.
Ewelina KulikowskiResverlogix Corporation, Calgary, Alberta, Canada.
Peter P TothCGH Medical Center, Sterling, Illinois, and Cicarrone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Norman WongResverlogix Corporation, Calgary, Alberta, Canada.
Michael SweeneyResverlogix Corporation, Calgary, Alberta, Canada.
Gregory G SchwartzDivision of Cardiology, University of Colorado School of Medicine, Aurora.
BETonMACE Investigators and Committees
Resverlogix (Canada) · CACGH Medical Center · USColumbia University · USImperial College London · GBMonash University · AUUniversity of California, Irvine · USUniversity of Colorado Denver · USUniversity of Wisconsin–Madison · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: Bromodomain and extraterminal proteins are epigenetic regulators of gene transcription. Apabetalone is a selective bromodomain and extraterminal protein inhibitor targeting bromodomain 2 and is hypothesized to have potentially favorable effects on pathways related to atherothrombosis. Pooled phase 2 data suggest favorable effects on clinical outcomes. Objective: To test whether apabetalone significantly reduces major adverse cardiovascular events. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled trial, conducted at 190 sites in 13 countries. Patients with an acute coronary syndrome in the preceding 7 to 90 days, type 2 diabetes, and low high-density lipoprotein cholesterol levels were eligible for enrollment, which started November 11, 2015, and ended July 4, 2018, with end of follow-up on July 3, 2019. Interventions: Patients were randomized (1:1) to receive apabetalone, 100 mg orally twice daily (n = 1215), or matching placebo (n = 1210) in addition to standard care. Main Outcomes and Measures: The primary outcome was a composite of time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, or stroke. Results: Among 2425 patients who were randomized (mean age, 62 years; 618 women [25.6%]), 2320 (95.7%) had full ascertainment of the primary outcome. During a median follow-up of 26.5 months, 274 primary end points occurred: 125 (10.3%) in apabetalone-treated patients and 149 (12.4%) in placebo-treated patients (hazard ratio, 0.82 [95% CI, 0.65-1.04]; P = .11). More patients allocated to apabetalone than placebo discontinued study drug (114 [9.4%] vs 69 [5.7%]) for reasons including elevations of liver enzyme levels (35 [2.9%] vs 11 [0.9%]). Conclusions and Relevance: Among patients with recent acute coronary syndrome, type 2 diabetes, and low high-density lipoprotein cholesterol levels, the selective bromodomain and extraterminal protein inhibitor apabetalone added to standard therapy did not significantly reduce the risk of major adverse cardiovascular events. Trial Registration: ClinicalTrials.gov Identifier: NCT02586155.

Indexed as

Acute Coronary SyndromeBlood Chemical AnalysisBromodomain Containing ProteinsCardiovascular DiseasesCholesterol, HDLDiabetes Mellitus, Type 2Double-Blind MethodFemaleHumansKaplan-Meier EstimateMaleMiddle AgedMyocardial InfarctionProteinsQuinazolinonesStrokeapabetalonebromodomain and extra-terminal domain protein, humanBromodomain Containing ProteinsCholesterol, HDLProteinsQuinazolinones

Identifiers

PMID32219359
PMCPMC7101505
OpenAlexW3013716928

What Socratic holds

Textmetadata
Read underepoch 390

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 Socratic graph.