SynthesisThe oncologist2026
Cardiac safety profiles of first-generation vs second-generation BTK inhibitors: a meta-analysis.
Synthesis in The oncologist, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy and safety of tirabrutinib monotherapy in relapsed or refractory B-cell lymphomas/leukemia: a meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Ibrutinib in Elderly Patients with Chronic Lymphocytic Leukemia: Adverse Event Incidence, Management, and Outcomes in a Canadian Real-World Setting.Current oncology (Toronto, Ont.) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe first-generation Bruton's tyrosine kinase inhibitor (BTKi), ibrutinib, is associated with significant cardiotoxicity. Second-generation agents were developed to mitigate this risk and offer an improved safety profile. This systematic review and meta-analysis of six direct comparator studies compares the cardiac safety profiles of first- and second-generation BTKi.
methodsWe systematically searched Medline, Embase, and Cochrane for studies directly comparing first- and second-generation BTKi. Data from 6 studies, encompassing 14 455 patients (12 816 in the first-generation arm and 1639 in the second-generation arm), were included. The primary outcomes were the incidence of atrial fibrillation (AF) and cardiac events, defined by the Medical Dictionary for Regulatory Activities system organ class. All pooled analyses were conducted using a random-effects model. Publication bias was evaluated visually using a funnel plot, quantitatively with Egger's regression test, and corrected using the Duval and Tweedie trim-and-fill method.
resultsCompared to second-generation agents, ibrutinib was associated with a significantly higher risk of AF (OR 2.50, 95% CI, 1.97-3.17), total cardiac events (OR 1.53, 95% CI, 1.18-1.99), and heart failure (OR 2.08, 95% CI, 1.13-3.83). This translated to a 3-fold higher rate of treatment discontinuation for a cardiac cause (OR 3.32, 95% CI, 1.46-7.55). No significant difference in all-cause mortality was found.
conclusionSecond-generation BTKi may provide a more favorable cardiovascular safety profile than ibrutinib, resulting in fewer key cardiac events and less treatment-limiting toxicity. These findings should inform clinical decision-making, especially for patients with increased risk for cardiovascular disease.
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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 OpenQuestion graph.