Rabinstein, Alejandro A.

Abstract Background and aims Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches and reversible multifocal cerebral arterial narrowing. Although prognosis is generally favorable, a subset of patients develops cerebrovascular complications that may drive long-term disability; this study aims to identify factors associated with these complications. Methods We retrospectively reviewed 348 patients with probable or definite RCVS evaluated at Mayo Clinic between 2010-2023. Diagnostic criteria were adapted from RCVS2 and ICHD-3. The primary outcome was a composite of ischemic stroke, non-aneurysmal subarachnoid hemorrhage, and intracerebral hemorrhage; secondary outcome was poor functional status (modified Rankin Scale ≥2 within one year). Univariable and multivariable logistic regression identified predictors of these outcomes. Results Cerebrovascular complications occurred in 37.6% of patients and were the strongest determinant of poor functional outcome (aOR 5.05, 95% CI 2.04–12.51). On multivariable analysis, older age (aOR per year 1.02, 95% CI 1.00–1.04) and angiographically visible vasoconstriction (aOR 3.14, 95% CI 1.85–5.33) were independently associated with higher risk of cerebrovascular complications, whereas male sex (aOR 0.55, 95% CI 0.30–0.99), thunderclap headache at presentation (aOR 0.30, 95% CI 0.11–0.86), and sexual activity as a trigger (aOR 0.19, 95% CI 0.08–0.42) were associated with lower risk of these complications. Conclusions Cerebrovascular complications are common and strongly predict disability. Angiographic vasoconstriction and older age identify patients at higher risk, whereas thunderclap headache and sexual activity as a trigger mark a more benign phenotype. These findings may guide early risk stratification and help tailored monitoring strategies. Conflict of interest Name of author: nothing to disclose.

Background Resuming anticoagulation in patients with mechanical heart valves after intracranial hemorrhage presents a clinical dilemma. The optimal timing must balance the risk of thromboembolism against hemorrhagic expansion. Prior studies have addressed this issue, but most were limited by small sample sizes. This systematic review and meta‐analysis aimed to determine the optimal timing for anticoagulation resumption in this population. Methods We conducted a systematic review and meta‐analysis using PubMed, Embase, Web of Science, and Scopus from database inception to August 23, 2024. The target population included adults with intracranial hemorrhage who required anticoagulation for mechanical heart valves. Results Thirteen studies involving 788 patients were included: 12 retrospective and 1 prospective observational study. While off anticoagulation, 32 patients developed ischemic stroke, with a pooled event rate of 5.23% (95% CI, 3.80–7.20%) and negligible heterogeneity ( I 2 = 0%). The pooled average time to stroke was 8.08 days (95% CI, 1.99–14.18). After anticoagulation resumption, 73 patients experienced hemorrhagic recurrence, corresponding to a pooled event rate of 10.95%, with nonsignificant heterogeneity ( I 2 = 40.4%). Conclusions Withholding anticoagulation for up to 7 days after intracranial hemorrhage in patients with mechanical heart valves appears relatively safe. Hemorrhagic recurrence after resumption was more common than ischemic stroke during interruption. However, the included studies were observational and carried serious or critical risk of bias. Prospective multicenter studies, and ideally randomized trials, are needed to provide more definitive evidence.

Antithrombotic therapy plays an important role in reducing stroke recurrence. For noncardioembolic stroke, multiple trials have demonstrated the efficacy of antiplatelet monotherapy for secondary stroke prevention. In select situations, such as short-term treatment in the acute period after a minor stroke or transient ischemic attack, dual-antiplatelet therapy has demonstrated superiority to monotherapy. Multiple trials have tested more aggressive strategies using long-term combination antiplatelet medications or full-dose anticoagulation with limited evidence of a reduction in ischemic events but a relatively consistent increased risk of bleeding. Emerging new agents targeting factor XI/XIa may uncouple necessary hemostasis from pathological thrombosis and offer promise for enhancing secondary prevention of stroke without increasing bleeding. The recently positive OCEANIC-STROKE trial (Oral Factor Eleven A Inhibitor Asundexian as Novel Antithrombotic) testing dual-pathway inhibition with the factor XIa inhibitor asundexian in combination with antiplatelet therapy represents a major advance in antithrombotic therapy for noncardioembolic stroke. This review summarizes the current state of the evidence for antithrombotic therapy in secondary stroke prevention after noncardioembolic stroke and discusses completed and ongoing trials of novel factor XI/XIa inhibitors for stroke prevention.