Treatment of Myeloproliferative Neoplasms With Janus Kinase Inhibitors: A Meta‐Analysis of Cardiovascular Safety
Bibliographic record
Abstract
ABSTRACT Background Janus kinase inhibitors (JAKis) are an integral aspect of the management of myeloproliferative neoplasms (MPNs). Part of the clinical benefit derived from JAKis may be due to reductions in thrombosis, a potentially life‐threatening complication of MPNs. However, evidence has emerged of adverse cardiovascular effects secondary to JAKis. We conducted a first‐of‐a‐kind meta‐analysis of the cardiovascular safety of JAKis in the treatment of MPNs. Methods This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA). Systematic searches for studies comparing JAKi treatment to a control group were conducted. Studies reporting hypertension, major adverse cardiovascular events (MACE) and thromboembolic events were included in a meta‐analysis using a random‐effects model for the primary analysis, and fixed‐effects model for any subgroup analyses performed. Results A total of 23 publications, consisting of nine clinical trials and one retrospective analysis, met the inclusion criteria. This resulted in a pooled population of 2198 patients (JAKi n = 1145, Control n = 1053). In studies reporting thromboembolic events (n = 9), pooled analysis revealed a significantly lower rate of thromboembolic events in the JAKi group (incidence rate ratio (IRR): 0.52, 95% CI: 0.28–0.98, p = 0.04). This was primarily driven by ruxolitinib studies in myelofibrosis (MF) and polycythemia vera (PV) as when a subgroup analysis of these trials was performed (n = 7), an even more significant reduction in thromboembolic events with JAKi treatment was found (IRR: 0.41, 95%CI: 0.26–0.64, p < 0.001). There was no significant difference in MACE or hypertension between JAKi and control groups. Conclusion This meta‐analysis suggests that JAKi treatment of MPN was associated with a reduced risk of thromboembolic events; primarily driven by studies of ruxolitinib in PV and MF. Further prospective clinical trials are warranted to confirm these findings and characterise the cardiovascular profile of other JAKis and other types of MPNs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.014 | 0.025 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.014 | 0.054 |
| Bibliometrics | 0.004 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".