Evidence map›Paper›PMID 30785921›Full record

SynthesisPloS one2019

Ibrutinib increases the risk of hypertension and atrial fibrillation: Systematic review and meta-analysis.

Daniel Caldeira, Daniela Alves, João Costa, Joaquim J Ferreira, Fausto J Pinto

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing 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

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

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Guideline
  5. Guideline
  6. Trial
  7. Trial
  8. Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Trial
  9. Trial
  10. Trial
  11. Review
  12. Article
  13. Article
  14. Review
  15. Cardiovascular Toxicity of BTKi in Chronic B-Cell Malignancies.Reviews in cardiovascular medicine · 2026
    Review
  16. Review
  17. Review
  18. Cardiovascular Safety of Bruton Tyrosine Kinase Inhibitors: From Ibrutinib to Next-Generation Agents.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026
    Review
  19. Article
  20. Review

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Daniel CaldeiraServiço de Cardiologia, Hospital Universitário de Santa Maria (CHLN), CAML, Centro Cardiovascular da Universidade de Lisboa-CCUL, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisboa, Portugal.ORCID 0000-0002-2520-5673
Daniela AlvesHematology Department, Faculdade de Medicina, Universidade de Lisboa, Santa Maria University Hospital (CHLN), Lisbon, Portugal.
João CostaLaboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisboa, Portugal.
Joaquim J FerreiraLaboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisboa, Portugal.
Fausto J PintoServiço de Cardiologia, Hospital Universitário de Santa Maria (CHLN), CAML, Centro Cardiovascular da Universidade de Lisboa-CCUL, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisboa, Portugal.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionIbrutinib is an oral covalent inhibitor of Bruton's tyrosine kinase approved for the treatment of patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma and Waldenstrӧm's macroglobulinemia. Ibrutinib has an increased risk of atrial fibrillation but the mechanism is unknown, and hypertension may play a role in the pathogenesis of this adverse drug reaction.

methodsWe aimed to review the risk of hypertension and atrial fibrillation as adverse events associated with ibrutinib through a systematic review with meta-analysis of randomized controlled trials (RCTs) retrieved in December 2018 on MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov. The data were pooled using random-effects meta-analyses using the risk ratio (RR) with the 95% confidence interval (95%CI). The confidence on the pooled estimates was ascertained through the grading of recommendations assessment, development, and evaluation (GRADE) approach.

resultsThere were 8 eligible RCTs (2580 patients), all reporting safety data of interest. Ibrutinib was associated with a significant increase in the risk of hypertension with a RR of 2.82 (95%CI 1.52-5.23) with moderate quality evidence. Ibrutinib increased significantly the risk of atrial fibrillation with a RR of 4.69 (95%CI 2.17-7.64) with high quality evidence.

conclusionsIbrutinib was associated with significantly increased risks of both hypertension and atrial fibrillation.

Indexed as

AdenineAtrial FibrillationDatabases, FactualHumansHypertensionLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Mantle-CellPiperidinesProtein Kinase InhibitorsPyrazolesPyrimidinesRandomized Controlled Trials as TopicRiskAdenineibrutinibPiperidinesProtein Kinase InhibitorsPyrazolesPyrimidines

Identifiers

PMID30785921
PMCPMC6382095

What OpenQuestion holds

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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 OpenQuestion graph.