BACKGROUND AND OBJECTIVES Limited data exist on the safety of IV thrombolysis (IVT) for acute ischemic stroke (AIS) after dabigatran reversal with idarucizumab. We sought to evaluate the safety and efficacy of idarucizumab pretreatment in patients with AIS receiving IVT. METHODS A national registry-based study evaluated the safety and efficacy of IVT in this specific subgroup. We also conducted a systematic review and meta-analysis of cohort studies and case series, aiming to document the pooled rates of (1) symptomatic intracranial hemorrhage (sICH), (2) any intracranial hemorrhage, (3) 3-month mortality, and (4) the proportion of excellent (modified Rankin Scale [mRS] scores 0-1) and (5) good (mRS scores 0-2) functional outcome at 3 months among patients with AIS, who received IVT after dabigatran reversal with idarucizumab. Moreover, we sought to compare these outcomes between IVT-treated patients after dabigatran reversal with idarucizumab and IVT-treated patients without dabigatran pretreatment. RESULTS Thirteen cohorts including our nation-wide registry-based cohort and 1 case series comprising 553 patients with AIS (mean age: 75 years; male sex: 65%; median baseline NIH Stroke Scale score: 11 points) receiving idarucizumab before IVT were included in this meta-analysis. The pooled rate of sICH after IVT after idarucizumab administration was 4% (95% CI 1-9; I2 = 26%), while the pooled rates of any intracranial hemorrhage and 3-month mortality were 10% (95% CI 5-16; I2 = 24%) and 18% (95% CI 10-27; I2 = 0%), respectively. The pooled rates of excellent and good functional outcomes at 3 months were 56% (95% CI 27-83; I2 = 69%) and 70% (95% CI 57-81; I2 = 40%), respectively. The risk of sICH (risk ratio [RR] 1.86; 95% CI 0.91-3.80; I2 = 0%), any intracranial hemorrhage (RR 1.76; 95% CI 0.99-3.11; I2 = 8%), and 3-month mortality (RR 1.50; 95% CI 0.91-2.48; I2 = 0%) did not differ between patients with AIS receiving IVT with and without idarucizumab. Moreover, idarucizumab administration was associated with higher likelihood of achieving a 3-month good functional outcome (RR 1.35; 95% CI 1.11-1.65; I2 = 27%). DISCUSSION IVT for AIS after dabigatran reversal with idarucizumab seems to be safe and effective in observational studies with limited number of patients. Randomized-controlled clinical trials are warranted to provide robust evidence on the safety and efficacy of IVT in this specific AIS subgroup.

中文翻译：

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急性缺血性中风达比加群逆转后的溶栓：一项基于国家登记的研究和荟萃分析。


背景和目的 关于达比加群用 idarucizumab 逆转后静脉溶栓 (IVT) 治疗急性缺血性卒中 (AIS) 的安全性数据有限。我们试图评估 idarucizumab 预处理对接受 IVT 的 AIS 患者的安全性和有效性。方法 一项基于国家登记的研究评估了 IVT 在这一特定亚组中的安全性和有效性。我们还对队列研究和病例系列进行了系统回顾和荟萃分析，旨在记录 (1) 有症状颅内出血 (sICH)、(2) 任何颅内出血、(3) 3 个月死亡率和(4) 在用 idarucizumab 逆转达比加群后接受 IVT 的 AIS 患者中，3 个月时获得优异（改良 Rankin 量表 [mRS] 评分 0-1）和（5）良好（mRS 评分 0-2）功能结果的比例。此外，我们试图比较用 idarucizumab 逆转达比加群后接受 IVT 治疗的患者与未经达比加群预处理的 IVT 治疗患者之间的这些结果。结果 纳入了 13 个队列，包括我们的全国范围登记队列和 1 个病例系列，其中包括 553 名 AIS 患者（平均年龄：75 岁；男性：65%；基线 NIH 卒中量表评分中位数：11 分），在 IVT 前接受 idarucizumab在这个荟萃分析中。给予 idarucizumab 后 IVT 后 sICH 的汇总率为 4%（95% CI 1-9；I2 = 26%），而任何颅内出血和 3 个月死亡率的汇总率为 10%（95% CI 5-16） ; I2 = 24%) 和 18% (95% CI 10-27; I2 = 0%)。 3 个月时优异和良好功能结果的汇总率分别为 56% (95% CI 27-83; I2 = 69%) 和 70% (95% CI 57-81; I2 = 40%)。 sICH 风险（风险比 [RR] 1.86；95% CI 0.91-3。80； I2 = 0%）、任何颅内出血（RR 1.76；95% CI 0.99-3.11；I2 = 8%）和 3 个月死亡率（RR 1.50；95% CI 0.91-2.48；I2 = 0%）没有差异接受IVT（联合或不联合）idarucizumab 的 AIS 患者之间的比较。此外，给予 idarucizumab 与实现 3 个月良好功能结果的可能性较高相关（RR 1.35；95% CI 1.11-1.65；I2 = 27%）。讨论 在患者数量有限的观察性研究中，用 idarucizumab 逆转达比加群后进行 IVT 治疗 AIS 似乎是安全有效的。随机对照临床试验有必要为 IVT 在这一特定 AIS 亚组中的安全性和有效性提供有力的证据。