Bruton's tyrosine kinase inhibitors and cardiovascular risk: a meta-analysis
In brief
BTK inhibitors raise non-fatal ischemic cardiovascular events by about 66%
A meta-analysis of 17 phase-3 trials involving 6,799 patients with B-cell cancers found that treatment with BTK inhibitors increased the risk of non-fatal ischemic major adverse cardiovascular events by roughly two-thirds compared with control arms. The signal was driven mainly by ibrutinib and showed substantial study heterogeneity, highlighting the need for careful cardiovascular monitoring in these patients.
- Journal
- European heart journal (Q1)
- Published
- 8 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Joachim Alexandre, Jonaz Font, Stéphanie Haddad, Baptiste Delapierre, Ghandi Damaj, Damien Legallois, et al.
- PMID
- 42568037
- DOI
- 10.1093/eurheartj/ehag613
Why clinicians should know about it
- Picked for Cardiology and Cardiovascular Medicine (top studies of the week, 9 August 2026).
- Picked for Neurology (clinical) (top studies of the week, 9 August 2026).
- Picked for Oncology and Radiation Oncology (top studies of the week, 9 August 2026): BTK‑I increase non‑fatal ischemic MACE risk
- Picked for Public Health, Environmental and Occupational Health (top studies of the week, 9 August 2026).
Abstract
BACKGROUND AND AIMS: Bruton's tyrosine kinase inhibitors (BTK-I) affect platelet function, increasing bleeding risk, and are also associated with hypertension and atrial fibrillation. This study aimed to assess the risk of incident non-fatal ischaemic major adverse cardiovascular events (MACE) associated with BTK-I exposure through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: ClinicalTrials.gov, EudraCT, MEDLINE, and Cochrane CENTRAL were systematically searched to identify Phase 3 RCTs of BTK-I (ibrutinib, acalabrutinib, zanubrutinib) reporting non-fatal ischaemic MACE up to 19 December 2024. The primary outcome was the summary risk of incident non-fatal ischaemic MACE (defined as a partial MACE composite of myocardial ischaemic syndromes and ischaemic stroke/transient ischaemic attack) associated with BTK-I exposure vs controls in adults with B-cell malignancies. A random-effects meta-analysis for binary outcomes was performed using the Mantel-Haenszel method, with between-study heterogeneity estimated using the DerSimonian-Laird estimator, to derive pooled risk ratios with their 95% confidence intervals. RESULTS: Seventeen Phase 3 RCTs including 6799 patients were analysed (55.5% BTK-I arms). Most patients received ibrutinib (77.2%), followed by acalabrutinib (13.5%) and zanubrutinib (9.3%). BTK-I exposure was associated with an increased risk of non-fatal ischaemic MACE (risk ratio 1.66, 95% confidence interval 1.09-2.53, P = .02), with substantial heterogeneity (I2 = 70%). CONCLUSIONS: Based on adverse-event reporting from Phase 3 RCTs that does not permit adjustment for competing risks, BTK-I exposure is associated with an increased risk of non-fatal ischaemic MACE. REGISTRATION: PROSPERO, International Prospective Register of Systematic Reviews; registration number: CRD420251241020.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.