Timing of anticoagulation therapy resumption among non-valvular atrial fibrillation (NVAF) patients with prior intracranial haemorrhage

Purpose Resumption of anticoagulation therapy (OAC) in patients surviving from intracranial haemorrhage (ICH) is challenging. We aimed to evaluate impact of timing of resumption of OAC on clinical outcomes in NVAF patients with history of ICH. Methods Consecutive patients with NVAF with or without OAC who survived from an index ICH between January 2018 and July 2022 in 16 public hospitals in Hong Kong were identified and analyzed retrospectively. Resumption of OAC was substantiated by new prescription records obtained from electronic medical records. Patients were stratified by tertile of timing of OAC resumption: (i) never on OAC(as reference group); (ii) resume OAC<=7 months; (iii) resume OAC during 7-9months (iv) resume OAC >=9months; (v) discontinue permanently. Risks of recurrent ICH and ischemic stroke were estimated and compared, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for components of CHA2DS2VA and HASBLED scores. Results Of 969 patients who met inclusion criteria (mean age 77.9±11, female 41.7%), 42.9% (n=416) never put on OAC, 18.5%(n=179) had no resumption of OAC, 13.1% (n=127) resumed OAC<=7months, 12.1% (n=117) 7-9months, 13.4% (n=130) >=9 months, respectively. Among patients who resumed OAC, 6.1%(n=23) stepped up dosage, 16.6%(n=62) stepped down and 38.2%(n=143) remained original dosage; 14.7%(n=55) switched OAC agent. Timing of OAC resumption varied across different OAC agents (mean time from index to resumption in months: apixaban 13.4±11 months, dabigatran 10.5±6 months, edoxaban 19.3±13 months rivaroxaban 10.3±9 months, and warfarin 7.5±2 months, p=NS). During a median follow-up period of 1.7 (IQR: 0.4-3.2) years, resumption of OAC <=7 months was associated with increased risk of recurrent ICH (aSHR=1.99 (1.01-3.92) and composite adverse events(ICH and ischemic stroke) (aSHR=2.11(1.17-4.16) whereas no difference was observed between other groups (Table 1). An abrupt rise of incidence rates of ischemic stroke was observed among patients who resumed OAC >=7 months and with CHA2DS2VA >=4, although statistically significance was not reached (Figure 1). Conclusion Our real-world data revealed among patients with prior ICH, delayed resumption of OAC in patients with CHA2DS2VA >=4 may result in increased risk of ischemic stroke. Resumption of OAC <=7 months may be associated with more recurrent ICH and composite cerebrovascular events.