Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

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]; Pinteraction=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.

Antiplatelet use and CADASIL: a retrospective observational analysis.

OBJECTIVES: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is hallmarked by age-dependent accumulation of microangiopathy with antiplatelet medications commonly used for stroke prevention though without known therapeutic benefit. Our objective was to identify whether antiplatelet therapy impacted the incidence of acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH) in those with reported CADASIL. MATERIALS AND METHODS: Owing to the rarity of the disease, we performed a retrospective study of anonymized data from the international TriNetX Research Network (Oct 2015 through January 2021). Individuals had an ICD-10 code (I67.850) for CADASIL. The primary outcome was incidence of validated ICD-10 codes for AIS (I63) and ICH (I61) linked with unique hospital admission encounters. The primary exposure was use of an antiplatelet medication for at least 1 month prior to the primary outcome. Age-adjusted logistic regression was used for likelihood ratios. RESULTS: We identified 455 individuals: 36% female, 40 (8.8%) antiplatelet exposed. Those with antiplatelet use were older (antiplatelet: 61±12 years vs. unexposed: 57±14 years, p = 0.034) with similar rates of AIS [antiplatelet: 23%(9/40) vs. unexposed: 14%(60/415); p=0.18] and ICH [antiplatelet: 3%(1/40) vs. unexposed: 5%(19/415); p = 0.54) and without significant impact on age-adjusted AIS likelihood (OR 1.62, 95%CI 0.73-3.60, p=0.23). Sample size precluded ICH regression analyses. CONCLUSIONS: Our data suggests that antiplatelet use did not significantly impact incidence of AIS or ICH within a group of individuals with suspected CADASIL This study highlights the need for further understanding of the pathophysiology of CADASIL to lead to disease modifying treatments.

Intravenous Thrombolysis in Patients With Cervical Artery Dissection: A Secondary Analysis of the STOP-CAD Study.

OBJECTIVES: Cervical artery dissection (CeAD) accounts for 25% of ischemic strokes in young adults. This study evaluated the benefits and harms of intravenous thrombolysis (IVT) in patients presenting with spontaneous CeAD and acute ischemic stroke symptoms. METHODS: This analysis used data from the retrospective STOP-CAD study and included patients with spontaneous CeAD who presented within 1 day of acute ischemic stroke symptoms. Patients were dichotomized into those who received IVT and those managed without IVT. We assessed the association between IVT and 90-day functional independence (modified Rankin Scale scores 0-2) and the incidence of symptomatic intracranial hemorrhage (ICH, defined as ICH causing new or worsening neurologic symptoms within 72 hours after CeAD diagnosis). RESULTS: This study included 1,653 patients from the original STOP-CAD cohort of 4,023. The median age was 49 years, and 35.1% were women; 512 (31.0%) received IVT. IVT was associated with 90-day functional independence (adjusted odds ratio [aOR] = 1.67, 95% CI 1.23-2.28, p = 0.001), but not with symptomatic ICH (aOR = 1.52, 95% CI 0.79-2.92, p = 0.215). DISCUSSION: In patients with spontaneous CeAD and suspected ischemic stroke, IVT improved functional outcomes, without increasing symptomatic ICH risk. These findings support current guideline recommendations to consider thrombolysis for otherwise eligible patients with CeAD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IVT significantly increases the probability of 90-day functional independence in patients with CeAD.

Pre-stroke Adherence to Hypertension Medications in a Bi-racial United States Stroke Belt.

INTRODUCTION: Blood pressure is not optimally reduced in 3 of 4 patients with hypertension (HTN) in the United States. AIM: We analyzed for factors associations with premorbid non-adherence to HTN medications in acute stroke patients. METHODS: This cross-sectional study included 225 acute stroke patients with self-reported adherence to HTM medications in a stroke registry in the Southeastern United States. We defined medication non-adherence as < 90% of prescribed. Logistic regression analyzed demographic and socioeconomic factors for prediction of adherence. RESULTS: There were 145 (64%) patients with adherence and 80 (36%) with non-adherence. The likelihood of adherence to HTN medications was decreased among black patients, OR 0.49 (95% CI 0.26-0.93), p = 0.03, and those without health insurance, OR 0.29 (95% CI 0.13-0.64), p = 0.002. Specific reasons for non-adherence were high medication cost in 26 (33%), side effects in 8 (10%), and other unspecified reasons in 46 (58%) patients. CONCLUSION: In this study, adherence to HTN medications was significantly lower among black patients and those without health insurance.

Small vessel disease is associated with later onset of major adverse cardiovascular events after acute cervicocerebral artery dissection.

BACKGROUND: Cerebral small vessel disease (CSVD) is common among the elderly and has been associated with an increased risk of major adverse cardiac events (MACE) and increased risk of long-term disability. Little is known whether CSVD affects outcomes after cervicocerebral artery dissection (CAD), which predominantly affects younger patients. Specifically, there is a paucity as to whether CSVD increases the risk of MACE after CAD and whether this risk is different for early versus late events. METHODS: We retrospectively analyzed 140 consecutive patients with acute CAD. We determined CSVD on MRI using the STRIVE criteria and calculated the CSVD sum score based on the individual CSVD components. For statistical analysis the CSVD burden was dichotomized to mild (score 0-1) versus severe (score 2-4). The primary outcome of interest was the 6-month MACE risk. Secondary outcomes of interest were early versus late MACE, stroke at presentation, and good 90-day outcome (modified Rankin Scale score 0-2). RESULTS: There was no difference in overall MACE between subjects when stratified by CSVD burden (10.1% versus 9.8%, Log-rank P = 0.953). We found that patients with severe CSVD had significantly more late MACE as compared to mild CSVD (9.8% versus 1.1%, P = 0.024). There was no significant difference in the prevalence of stroke at the time of CAD diagnosis (50.6% versus 47.1%, P = 0.690) and the 90-day disability-free survival in subjects with mild versus severe CSVD (93.7% versus 91.7%, P = 0.729). CONCLUSION: Severe CSVD burden was associated with a significantly greater risk of late MACE. CSVD assessment in CAD patients may aid risk stratification and treatment optimization.