Net Clinical Benefit of Left Atrial Appendage Occlusion After Intracerebral Hemorrhage in Atrial Fibrillation: A Focused Review and Benchmark-Adjusted Secondary Analysis
Background/Objectives: Atrial fibrillation (AF) after intracerebral hemorrhage (ICH) creates a therapeutic conflict: withholding oral anticoagulation may increase ischemic stroke risk, whereas resumption of anticoagulation may increase recurrent ICH. Left atrial appendage occlusion (LAAO) offers a nonpharmacologic alternative, but isolated stroke or bleeding rates do not describe the overall benefit–harm balance. This focused review examines net clinical benefit (NCB) as a decision framework for LAAO after ICH and presents a secondary benchmark-adjusted analysis derived from our prior systemaatic review and meta-analysis. Methods: Thirteen endocardial LAAO cohorts with complete data for ischemic stroke, recurrent ICH, major bleeding, and all-cause death contributed to the analysis. The component event data and prespecified severity weights were carried forward from the prior meta-analysis; the external benchmark comparison, study-level benchmark-adjusted NCB synthesis, and benchmark-sensitivity analyses were not part of that report and constitute the distinct secondary analysis presented here. Results: Prespecified external benchmark rates were 8.0, 2.0, 3.0, and 6.0 events per 100 patient-years, respectively. Unweighted and severity-weighted NCB were evaluated using both pooled-rate and study-level Hartung–Knapp random-effects approaches. Study-level pooled NCB was 12.20 events per 100 patient-years (95% CI, 8.61–15.79; I2 = 96%), and weighted NCB was 14.39 (95% CI, 8.84–19.94; I2 = 94%). Additional two-component analyses using PRESTIGE-AF reference rates yielded unweighted NCB estimates of 5.65 and 2.06 events per 100 patient-years for no-OAC and DOAC comparator scenarios, respectively. Excluding all-cause mortality from the original model yielded an unweighted NCB of 8.41. These exploratory results highlight the sensitivity of NCB estimates to comparator selection and endpoint composition. Conclusions: Contemporary randomized evidence, including PRESTIGE-AF, CLOSURE-AF, and CHAMPION-AF, reinforces that benefit–harm balance is population-, comparator-, endpoint-, and time-horizon-dependent. Accordingly, these NCB estimates should be interpreted as decision-analytic and hypothesis-generating rather than causal treatment effects. ICH-specific randomized comparisons remain essential.
Authors
- IOANNIS A. PARASKEVAIDIS (ORCID: https://orcid.org/0000-0002-7764-6411)
- Basel Ramlawi (ORCID: https://orcid.org/0000-0002-0471-0910)
- Serge Sicouri (ORCID: https://orcid.org/0000-0002-1822-768X)
- Christos Kourek (ORCID: https://orcid.org/0000-0003-4348-2153)
- Dimitrios E. Magouliotis (ORCID: https://orcid.org/0000-0001-5417-6392)
- Αlexandros Briasoulis (ORCID: https://orcid.org/0000-0002-5740-9670)
- Andrew V. Xanthopoulos (ORCID: https://orcid.org/0000-0002-9439-3946)
Institutions
- Lankenau Institute for Medical Research (US)
- National and Kapodistrian University of Athens (GR)
- Lankenau Medical Center (US)
- University Hospital of Larissa (GR)
Publication Details
- Journal
- Journal of Clinical Medicine
- Published
- 2026-11-05
- DOI
- https://doi.org/10.3390/jcm15218612
- Primary Topic
- Atrial Fibrillation Management and Outcomes
- Type
- article
- Field-Weighted Citation Impact
- 0.00