Bavarsad Shahripour, Reza

BACKGROUND: Patients with cervical artery dissection (CeAD) may experience a recurrent dissection, but its frequency, risk factors, and clinical implications are not well defined. We aimed to determine the risk, associated factors, and clinical impact of recurrent CeAD. METHODS: The STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection) was a multicenter international retrospective observational study of patients with CeAD treated between January 2015 and June 2022. Recurrent dissection was defined as a CeAD occurring at least 7 days after the diagnosis of the index event that affects a different artery or a different segment of the same artery. Patients were followed from day 7 up to 2 years. The absolute risk of recurrent CeAD over time was calculated using Kaplan-Meier survival estimates. Multivariable logistic and Cox regression models were used to assess predictors of CeAD recurrence. RESULTS: Of the 4023 patients included in STOP-CAD, 3836 (median age 46 years, 45% women) were eligible for this analysis. During a median (interquartile range) follow-up of 295 (97–720) days, 88 (2.29%) patients had a CeAD recurrence. Median time-to-recurrent CeAD was 53 (interquartile range, 18–157) days. The estimated risk of recurrent CeAD at 2 years was 3.22% (95% CI, 2.59%–4.00%). In multivariable analyses, younger age (adjusted odds ratios, 0.98 [95% CI, 0.96–0.99]), migraine (adjusted odds ratio, 1.88 [95% CI, 1.14–3.07]), and fibromuscular dysplasia (adjusted odds ratio, 2.90 [95% CI, 1.66–5.06]) were associated with CeAD recurrence, while presenting with an ischemic stroke was associated with a lower likelihood of recurrence (adjusted odds ratio, 0.47 [95% CI, 0.29–0.75]). These associations with CeAD recurrence over time were confirmed by Cox regression analyses. Among the 88 patients with recurrent CeAD, only 5 had accompanying ischemic events (3 strokes, 2 transient ischemic attacks). CONCLUSIONS: In this retrospective study, recurrent CeAD was uncommon, approximately half of the events were diagnosed within the first 2 months of the index event, and recurrent events rarely caused new ischemic events. Younger age, migraine, absence of ischemic stroke at presentation, and signs of fibromuscular dysplasia may help identify high-risk patients.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P =0.02; I 2 =0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P =0.03, I 2 =0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

Background: Whether thrombolysis improves outcomes in non-arteritic central retinal artery occlusion (naCRAO) is uncertain. We aimed to evaluate the rate of visual recovery after intra-venous thrombolysis (IVT) or intra-arterial thrombolysis (IAT) administration of tissue plasminogen activator (tPA) or urokinase among patients with naCRAO and explore the parameters affecting the final visual acuity (VA). Aim: We systematically searched six databases. Logarithm of the minimum angle of resolution (logMAR) and VA of ⩾20/100 were used to quantify visual recovery. To explore the role of other factors on visual recovery, we defined two models for studies with aggregated data (designs 1 and 2) and 16 models for individual participant data (IPD, models 1–16). Summary of Review: We included data from 771 patients out of 72 publications in nine languages. Visual improvement for ⩾0.3 logMAR was reported in 74.3% of patients who received IVT-tPA within 4.5 h (CI: 60.9–86.0%; unadjusted rate: 73.2%) and 60.0% of those who received IAT-tPA within 24 h (CI: 49.1–70.5%; unadjusted rate: 59.6%). VA of ⩾20/100 was observed among 39.0% of patients after IVT-tPA within 4.5 h and 21.9% of those with IAT-tPA within 24 h. IPD models highlighted the association between improved visual outcomes and VA at presentation, at least 2 weeks follow-up before reporting the final VA, antiplatelet therapy, and shorter symptom onset to thrombolysis window. Conclusion: Early thrombolytic therapy with tPA is associated with enhanced visual recovery in naCRAO. Future studies should refine the optimum time window for thrombolysis in naCRAO.