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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 January 2, 2024 e49

Joglar et al 2023 Guideline for the Diagnosis and Management of Atrial Fibrillation

and position of the prosthetic.9–11 These rates are even higher in patients with concurrent AF but are significantly reduced with the use of VKAs. Data are limited that explore the safety and timing of anticoagulation resumption in patients with ICH and high-risk valvular disease. In 1 observational analysis of 137 patients with ICH and mechanical heart valves, resuming anticoagulation within 2 weeks from index ICH was associated with increased hemorrhagic complications (HR, 7.06 [95% CI, 2.33-21.37]).1 However, in balancing the risk of hemorrhagic with thrombotic complications, the optimal window of resumption was found to be between 1 and 2 weeks post-ICH after weighing individual patient factors (Table 17). 2.	 Anticoagulation is associated with up to 25% of

ICHs and is associated with worse functional outcomes and higher mortality.12–15 After ICH, anticoagulation is generally held in the acute setting. Decisions regarding the appropriateness and timing of resumption are complex given the limited amount of randomized data addressing risks and benefits in this population. Previous observational reports evaluating risk of recurrent ICH, thromboembolism, and mortality in patients with nonvalvular AF have suggested possible reduction in thromboembolic risk and mortality with resumption of anticoagulation but are limited by discordant patient populations and study designs, predominant use of VKAs, and potential selection biases.16–22 In a meta-analysis of 2452 patients with AF and ICH, resumption of OACs was associated with lower risk of ischemic stroke (RR, 0.46 [95% CI, 0.29-0.72]) and no difference in risk of recurrent ICH compared with patients in whom anticoagulation was not resumed2 (Table 17). However, data are limited on the optimal timing for resumption. In an analysis of 2619 ICH survivors with AF, a composite net benefit minimizing risk of bleeding and thromboembolic complications occurred when anticoagulation was resumed at 7 to 8 weeks after ICH.3 In a retrospective study that included 1752 patients with OAC-related ICH across 3 Danish registries, anticoagulation resumed a median of 34 days was associated with an adjusted HR of ischemic stroke, systemic embolism, and all-cause mortality of 0.55 (95% CI, 0.39-0.78) compared with no anticoagulation.4 In another meta-analysis of 8 observational studies, resuming OAC was associated with reduced risk of ischemic stroke without increased risk of recurrent ICH at a median time to resumption of 10 to 39 days5 (Table 17). Of note, DOACs have been associated with lower rates of major bleeding complications compared with VKAs.23

3 Anticoagulation is used for stroke risk reduction

in patients with AF at risk of thromboembolism. For some patients, however, risk of recurrent ICH may be prohibitively high with anticoagulation. Cerebral amyloid angiopathy is the most common cause of lobar hemorrhage in older adults and is associated with annual ICH recurrence risk that ranges from 5% in patients with isolated microhemorrhages to 26.9% in patients with associated cortical superficial siderosis.24 Thus, in patients with AF and cerebral amyloid angiopathy-related ICH, alternative strategies for secondary stroke prevention are often pursued. The LAA is considered the most common site for thrombus formation in patients with AF.25,26 Two RCTs—PROTECT AF study and PREVAIL study—compared rates of stroke and mortality after LAA closure versus VKA in patients with AF.6,7 In a meta-analysis examining 5-year outcomes in the 2 RCTs, LAA closure was associated with significant reductions in hemorrhagic stroke, disabling and fatal stroke, and all-cause mortality, with comparable rates of stroke and systemic embolism compared with warfarin.27 Of note, both studies excluded patients who were not candidates for anticoagulation. Additionally, newer treatment options such as epicardial LAA clipping are emerging for stroke prevention without need for postprocedure APT.28,29

Table 17.  Risk Factors for Thromboembolic Complications and Recurrent ICH Factors Associated With High Risk of Thromboembolism Factors Associated With High Risk of Recurrent ICH Mechanical heart valve Suspected cerebral amyloid angiopathy Rheumatic valve disease Lobar IPH Previous history of stroke/ thromboembolism Older age Hypercoagulable state (eg, active malignancy, genetic thrombophilia) >10 cerebral microbleeds on MRI High CHA2DS2-VASc score (>5) Disseminated cortical superficial siderosis on MRI

Poorly controlled hypertension Previous history of spontaneous ICH Genetic/acquired coagulopathy Untreated symptomatic vascular malformation or aneurysm

CHA2DS2-VASc indicates congestive heart failure, hypertension, age ≥75 y (doubled), diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism (doubled), vascular disease, age 65 to 74 y, sex category; ICH, intracranial hemorrhage; IPH, intraparenchymal hemorrhage; and MRI, magnetic resonance imaging.

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