Evidence map›Paper›PMID 24911432›Full record

SynthesisPloS one2014

Twice- or once-daily dosing of novel oral anticoagulants for stroke prevention: a fixed-effects meta-analysis with predefined heterogeneity quality criteria.

Andreas Clemens, Herbert Noack, Martina Brueckmann, Gregory Y H Lip

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

Synthesis in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

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

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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

4 authors.

Andreas ClemensCenter for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Mainz, Germany; Global Biostatistics and Data Management, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Herbert NoackCorporate Division Medicine, Global Therapeutic Area Cardiovascular, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Martina BrueckmannCorporate Division Medicine, Global Therapeutic Area Cardiovascular, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
Gregory Y H LipUniversity of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA number of novel oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) are in clinical use for various indications. The dosing regimens differ between twice-daily and once-daily dosing for the prevention of stroke in patients with atrial fibrillation. With the availability of the results from four phase 3 studies (>70,000 patients), we explored whether twice-daily or once-daily dosing provides better risk-benefit balance among novel oral anticoagulants.

methodsWe conducted a strict, stepwise, fixed-effects meta-analysis with predefined heterogeneity quality criteria to generate the most appropriate common estimates for twice-daily (BID) or once-daily (QD) dosing regimens. An indirect comparison of these dosing regimens with fixed-effects meta-analysis common estimates (where available), or individual compound results, was done respectively.

resultsComparing indirectly BID vs QD dosing regimens resulted in hazard ratios (HR [95% confidence interval]) for stroke and systemic embolism of 0.75 (0.58-0.96) for dabigatran 150 mg BID, and 0.91 (0.73-1.13) for apixaban BID vs the QD dosing regimen. For ischemic stroke, the HR of BID vs QD was 0.85 (0.69-1.05). For intracranial hemorrhage, BID vs rivaroxaban QD was 0.57 (0.37-0.88) and, vs edoxaban QD, 0.81 (0.54-1.22). Due to heterogeneity, common estimates for major bleeding QD or BID were not justified, therefore indirect comparison of regimens were not possible. All non-vitamin K antagonist oral anticoagulants reduced all-cause mortality vs warfarin with a HR of 0.90 (0.86-0.96) without differences between regimen.

conclusionsBased on the available phase 3 study evidence, the twice-daily dosing regimen of non-vitamin K antagonist oral anticoagulants appears to offer a more balanced risk-benefit profile with respect to stroke prevention and intracranial hemorrhage.

Indexed as

PremedicationAdministration, OralAnticoagulantsDrug Administration ScheduleHumansStrokeTreatment OutcomeAnticoagulants

Identifiers

PMID24911432
PMCPMC4049736

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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.