D'Anna Lucio, Prandin Gabriele, Pirera Edoardo, Sacco Simona, Veltkamp Roland, Korompoki Eleni, Gigli Marta, Paciaroni Maurizio, Gorog Diana A, Favruzzo Francesco, Kanagaratnam Prapa, Lim Boom, Zhang Liqun, Simister Robert J, Valente Mariarosaria, Gigli Gian Luigi, Foschi Matteo, Merlino Giovanni
Department of Stroke and Neuroscience, Charing Cross Hospital, Imperial College London NHS Healthcare Trust, United Kingdom.
Department of Brain Sciences, Imperial College London, United Kingdom.
Neurology. 2025 Oct 21;105(8):e214184. doi: 10.1212/WNL.0000000000214184. Epub 2025 Sep 25.
In patients with mechanical heart valves (MHVs), anticoagulation (AC) interruption after intracranial hemorrhage (ICH) poses a clinical dilemma because of competing risks of ischemic complications and hemorrhagic recurrence. To date, the optimal timing for resuming vitamin K antagonists (VKAs) remains unclear. The aim of this meta-analysis was to quantify the risks of ischemic stroke and recurrent ICH associated with VKA resumption in this population and explore the temporal risk dynamics.
We systematically searched PubMed, Embase, and Cochrane Library from inception to December 2023 for studies reporting ischemic or hemorrhagic outcomes in adults with MHVs who experienced ICH and were considered for VKA resumption. Primary outcomes were ischemic stroke before AC resumption and recurrent ICH after AC resumption. Random-effects meta-analyses were performed. Meta-regressions assessed whether timing of resumption influenced risk. Risk trajectories were estimated using a model-based approach.
Nine studies were included, comprising 435 patients with MHVs with confirmed ICH included in the pooled analysis. The mean age ranged from 54.1 to 75 years; 31.3% were female. The pooled incidence of recurrent ICH after AC reinitiation was 11.4% (95% CI 8.2-15.6; = 0%), the incidence of ischemic stroke during AC suspension was 6.1% (95% CI 4.1-8.9; = 0%), valve thrombosis occurred in 3.3% (95% CI 1.9-5.6; = 0%), and mortality occurred in 4.9% (95% CI 2.0-11.5; = 37%). Meta-regression demonstrated a significant inverse association between time to AC resumption and risk of recurrent ICH (regression coefficient -0.039; 95% CI -0.093 to 0.015; = 0.13), corresponding to an approximate 50% relative reduction in risk at 11 days after ICH. No significant time-dependent association was observed for ischemic stroke (coefficient -0.013; 95% CI -0.065 to 0.039; = 0.61).
In patients with MHVs who experienced an ICH, this meta-analysis found that resumption of AC was associated with a recurrent ICH rate of 11.4% and an ischemic stroke rate of 6.1% during AC suspension. Meta-regression suggested a lower risk of recurrent ICH with later AC resumption, with a potential risk reduction at approximately 11 days after ICH. No time-dependent increase in ischemic stroke was observed. Limitations include the retrospective design of most studies and heterogeneous AC timing across cohorts.
在机械心脏瓣膜（MHV）患者中，颅内出血（ICH）后抗凝（AC）中断会带来临床困境，因为存在缺血性并发症和出血复发的相互竞争风险。迄今为止，恢复维生素K拮抗剂（VKA）的最佳时机仍不明确。本荟萃分析的目的是量化该人群中与恢复VKA相关的缺血性卒中及ICH复发风险，并探讨时间风险动态变化。
我们系统检索了从创刊至2023年12月的PubMed、Embase和Cochrane图书馆，以查找报告有ICH且考虑恢复VKA的成年MHV患者缺血性或出血性结局的研究。主要结局为恢复AC前的缺血性卒中以及恢复AC后的ICH复发。进行随机效应荟萃分析。荟萃回归评估恢复时间是否影响风险。使用基于模型的方法估计风险轨迹。
纳入9项研究，汇总分析中包括435例确诊为ICH的MHV患者。平均年龄在54.1至75岁之间；31.3%为女性。重新开始AC后ICH复发的汇总发生率为11.4%（95%CI 8.2 - 15.6；I² = 0%），AC中断期间缺血性卒中的发生率为6.1%（95%CI 4.1 - 8.9；I² = 0%），瓣膜血栓形成发生率为3.3%（95%CI 1.9 - 5.6；I² = 0%），死亡率为4.9%（95%CI 2.0 - 11.5；I² = 37%）。荟萃回归显示，恢复AC的时间与ICH复发风险之间存在显著负相关（回归系数 -0.039；95%CI -0.093至0.015；P = 0.13），相当于ICH后11天时风险相对降低约50%。未观察到缺血性卒中与时间相关的显著关联（系数 -0.013；95%CI -0.065至0.039；P = 0.61）。
在发生ICH的MHV患者中，本荟萃分析发现恢复AC与ICH复发率11.4%以及AC中断期间缺血性卒中发生率6.1%相关。荟萃回归表明，AC恢复时间越晚，ICH复发风险越低，在ICH后约11天时可能降低风险。未观察到缺血性卒中随时间增加。局限性包括大多数研究为回顾性设计以及各队列中AC时间存在异质性。
