Combined Anticoagulation and Antiaggregation in Acute Cervical Artery Dissection.
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SUBMITTER: von Gottberg P
PROVIDER: S-EPMC8509613 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceExtracranial carotid and vertebral artery dissection is an important cause of stroke, particularly in younger individuals. In some but not all observational studies, it has been associated with a high risk of recurrent stroke. Both antiplatelet agents (APs) and anticoagulants (ACs) are used to reduce stroke risk, but whether 1 treatment strategy is more effective is unknown.ObjectiveTo determine whether AP or AC therapy is more effective in preventing stroke in cervical dissection and the risk of recurrent stroke in a randomized clinical trial setting. A secondary outcome was to determine the effect on arterial imaging outcomes.Design, setting, and participantsRandomized, prospective, open-label international multicenter parallel design study with central blinded review of both clinical and imaging end points. Recruitment was conducted in 39 stroke and neurology secondary care centers in the United Kingdom and 7 centers in Australia between February 24, 2006, and June 17, 2013. One-year follow-up and analysis was conducted in 2018. Two hundred fifty participants with extracranial carotid and vertebral dissection with symptom onset within the last 7 days were recruited. Follow-up data at 1 year were available for all participants.InterventionsRandomization to AP or AC (heparin followed by warfarin) for 3 months, after which the choice of AP and AC agents was decided by the local clinician.Main outcomes and measuresThe primary end point was ipsilateral stroke and death. A planned per protocol (PP) analysis was performed in patients meeting the inclusion criteria following central review of imaging to confirm the diagnosis of dissection. A secondary end point was angiographic recanalization in those with imaging confirmed dissection.ResultsTwo hundred fifty patients were randomized (118 carotid and 132 vertebral), 126 to AP and 124 to AC. Mean (SD) age was 49 (12) years. Mean (SD) time to randomization was 3.65 (1.91) days. The recurrent stroke rate at 1 year was 6 of 250 (2.4%) on ITT analysis and 5 of 197 (2.5%) on PP analysis. There were no significant differences between treatment groups for any outcome. Of the 181 patients with confirmed dissection and complete imaging at baseline and 3 months, there was no difference in the presence of residual narrowing or occlusion between those receiving AP (n = 56 of 92) vs those receiving AC (n = 53 of 89) (P = .97).Conclusions and relevanceDuring 12 months of follow-up, the number of recurrent strokes was low. There was no difference between treatment groups in outcome events or the rate of recanalization.Trial registrationISRCTN.com Identifier: CTN44555237.
| S-EPMC6563567 | biostudies-literature
Project description:Background and objectivesIn young people aged < 50 years, cervical artery dissection (CeAD) is among the most common causes of stroke. Currently, there is no consensus regarding the safest and most effective antithrombotic treatment for CeAD. We aimed to synthesize concrete evidence from studies that compared the efficacy and safety of antiplatelet (AP) versus anticoagulant (AC) therapies for CeAD.MethodsWe searched major electronic databases/search engines from inception till September 2021. Cohort studies and randomized controlled trials (RCTs) comparing anticoagulants with antiplatelets for CeAD were included. A meta-analysis was conducted using articles that were obtained and found to be relevant. Mean difference (MD) with 95% confidence interval (CI) was used for continuous data and odds ratio (OR) with 95% CI for dichotomous data.ResultsOur analysis included 15 studies involving 2064 patients, 909 (44%) of whom received antiplatelets and 1155 (56%) received anticoagulants. Our analysis showed a non-significant difference in terms of the 3-month mortality (OR 0.47, 95% CI 0.03-7.58), > 3-month mortality (OR 1.63, 95% CI 0.40-6.56), recurrent stroke (OR 0.97, 95% CI 0.46-2.02), recurrent transient ischaemic attack (TIA) (OR 0.93, 95% CI 0.44-1.98), symptomatic intracranial haemorrhage (sICH) (OR 0.38, 95% CI 0.12-1.19), and complete recanalization (OR 0.70, 95% CI 0.46-1.06). Regarding primary ischaemic stroke, the results favoured AC over AP among RCTs (OR 6.97, 95% CI 1.25-38.83).ConclusionOur study did not show a considerable difference between the two groups, as all outcomes showed non-significant differences between them, except for primary ischaemic stroke (RCTs) and complete recanalization (observational studies), which showed a significant favour of AC over AP. Even though primary ischaemic stroke is an important outcome, several crucial points that could affect these results should be paid attention to. These include the incomplete adjustment for the confounding effect of AP-AC doses, frequencies, administration compliance, and others. We recommend more well-designed studies to assess if unnecessary anticoagulation can be avoided in CeAD.
| S-EPMC9433613 | biostudies-literature
Project description:Objective: The optimal management for cervical artery dissection (CAD) is uncertain. This study aimed to summarize the current randomized controlled trials (RCTs) to compare the efficacy and safety of antiplatelet and anticoagulation therapies for CAD. Methods: A literature search was conducted in the major databases, such as MEDLINE, Embase, and the Cochrane Library. Only the RCTs comparing the antiplatelet and anticoagulation therapies for the patients with CAD were included. Combined estimates of the relative risk (RR) of antiplatelet vs. anticoagulation were analyzed. Heterogeneity was measured using the I 2 statistical analysis. The analyses were performed in the intention-to-treat (ITT) and per-protocol (PP) population, respectively. Results: Two RCTs involving 444 patients in the ITT population and 370 patients in the PP population were included. The quality of studies was high overall. In the ITT population, compared with the patients in the anticoagulation group, the patients in the antiplatelet group showed a higher rate of ischemic stroke within 3 months (RR = 6.73 [95% CI, 1.22-37.15], I 2 = 0%, P = 0.029). No difference between these two treatment groups was found for the outcomes of transient ischemic attack (RR = 0.37 [95% CI, 0.09-1.58], I 2 = 0%, P = 0.181), intracranial hemorrhage (RR = 0.33 [95% CI, 0.01-7.98], I 2 = 0%, P = 0.494), major extracranial bleeding (RR = 0.31 [95% CI, 0.01-7.60], I 2 = 0%, P = 0.476), or the composite of these outcomes within 3 months. For the PP population, the results of the meta-analysis of outcomes between the antiplatelet and anticoagulation groups were consistent with the ITT population. Conclusions: Compared with the antiplatelet group, the anticoagulation group has a lower risk of ischemic stroke without increasing bleeding risk when treating CAD. Anticoagulation seems to be superior over the antiplatelet in treating CAD but needs to be further tested by specifying several issues, such as location, initial symptom types, and treatment protocols.
| S-EPMC8651981 | biostudies-literature
Project description:BackgroundGenetic and environmental risk factors are assumed to contribute to the susceptibility to cervical artery dissection (CeAD). To explore the role of genetic imbalance in the etiology of CeAD, copy number variants (CNVs) were identified in high-density microarrays samples from the multicenter CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study and from control subjects from the CADISP study and the German PopGen biobank. Microarray data from 833 CeAD patients and 2040 control subjects (565 subjects with ischemic stroke due to causes different from CeAD and 1475 disease-free individuals) were analyzed. Rare genic CNVs were equally frequent in CeAD-patients (16.4%; n=137) and in control subjects (17.0%; n=346) but differed with respect to their genetic content. Compared to control subjects, CNVs from CeAD patients were enriched for genes associated with muscle organ development and cell differentiation, which suggests a possible association with arterial development. CNVs affecting cardiovascular system development were more common in CeAD patients than in control subjects (p=0.003; odds ratio (OR) =2.5; 95% confidence interval (95% CI) =1.4-4.5) and more common in patients with a familial history of CeAD than in those with sporadic CeAD (p=0.036; OR=11.2; 95% CI=1.2-107).ConclusionThe findings suggest that rare genetic imbalance affecting cardiovascular system development may contribute to the risk of CeAD. Validation of these findings in independent study populations is warranted.
| S-EPMC5345335 | biostudies-literature
Project description:Spontaneous coronary artery dissection (SCAD) is a relatively rare and frequently misdiagnosed disease. The current knowledge of its pathophysiology and management is limited and based mostly on hypotheses. We present a patient with recurrent SCAD whose condition worsened soon after discontinuation of anticoagulation, prompting us to question the current management and review the evidence about pathophysiology, anticoagulation, and antiplatelet therapy.
| S-EPMC9112293 | biostudies-literature
Project description:Cervical artery dissection (CeAD) occurs in healthy young individuals and often entails ischemic stroke. Skin biopsies from most CeAD-patients show minor connective tissue alterations. We search for rare genetic deletions and duplication that may predispose to CeAD. Forty-nine non-traumatic CeAD-patients with electron microscopic (EM) alterations of their dermal connective tissue (EM+ patients) and 21 patients with normal connective tissue in skin biopsies (EM- patients) were analyzed. Affymetrix 6.0 microarrays (Affymetrix) from all patients were screened for copy number variants (CNVs). CNVs absent from 403 control subjects and from 2402 published disease-free individuals were considered as CeAD-associated. The genetic content of undentified CNVs was analyzed by means of the Gene Ontology (GO) Term Mapper to detect associations with biological processes. In 49 EM+ patients we identified 13 CeAD-associated CNVs harboring 83 protein-coding genes. In 21 EM- patients we found five CeAD-associated CNVs containing only nine genes (comparison of CNV gene density between the groups: Mann-Whitney P=0.039). Patients' CNVs were enriched for genes involved in extracellular matrix organization (COL5A2, COL3A1, SNTA1, P=0.035), collagen fibril organization COL5A2, COL3A1, (P=0.0001) and possibly for genes involved in transforming growth factor beta (TGF)-beta receptor signaling pathway (COL3A1, DUPS22, P=0.068). We conclude that rare genetic variants may contribute to the pathogenesis of CeAD, in particular in patients with a microscopic connective tissue phenotype.
| S-EPMC3499738 | biostudies-literature
Project description:IntroductionThe potential role of genetic alterations in cervical artery dissection (CeAD) pathogenesis is poorly understood. We aimed to identify pathogenic genetic variants associated with cervical artery dissection by using whole exome sequencing.Patients and methodsCeAD-patients with either a family history of cervical artery dissection (f-CeAD) or recurrent cervical artery dissection (r-CeAD) from the CeAD-databases of two experienced stroke centres were analysed by whole exome sequencing.Variants with allele frequency <0.05 and classified as pathogenic by predicting algorithms (SIFT or Polyphen-2) or the ClinVar database were explored. First, we analysed a panel of 30 candidate genes associated with arterial dissection (any site) or aneurysm according to the OMIM (online Mendelian Inheritance of Men) database. Second, we performed a genome-wide search for pathogenic variants causing other vascular phenotypes possibly related to cervical artery dissection.Findings were classified as CeAD-causing (pathogenic variants in genes from the arterial dissection or aneurysm panel) or suggestive (pathogenic variants in genes associated with other vascular phenotypes and variants of unknown significance in genes from the arterial dissection or aneurysm panel). All other variants were classified as benign/uncertain.ResultsAmong 43 CeAD-patients, 28 patients (17 pedigrees) had f-CeAD and 15 had r-CeAD. No CeAD-causing variants were identified in r-CeAD patients. Among f-CeAD-patients, 5/17 pedigrees carried CeAD-causing variants in COL3A1, COL4A1, COL4A3, COL4A4, COL5A1, COL5A2 and FBN1. Suggestive variants in ABCC6, COL3A1, COL5A2, MEF2A, and RNF213 were detected in three pedigrees with f-CeAD and six patients with r-CeAD.Discussion and conclusion: CeAD-causing variants were rare and exclusively found in f-CeAD-patients, suggesting differences between the genetic architectures of f-CeAD and r-CeAD. The identified variants indicate a high genetic heterogeneity of the study sample.
| S-EPMC6921947 | biostudies-literature
Project description:IntroductionCervical artery dissection, including carotid and vertebral artery dissection, is an important cause of stroke in the young. Risk of developing cervical artery dissection has been associated with physical activity in various forms and has been presumed to be related to minor trauma and mechanical stretching of the cervical arteries. This systematic review will aim to synthesise data on the risk of recurrent cervical artery dissection after an initial dissection. This information may be applied to further understand the natural history of this disease, and potentially to help direct evidence-based discussions on safe return to activity after dissection.Methods and analysisA broad search of multiple electronic databases (Medline, Embase, Cochrane Central Register of Controlled Trials and Web of Science) will be conducted to identify studies published as of 13 November 2019, examining all-comers with cervical artery dissection observed over time. Studies will be screened by two independent reviewers in a two-level process to determine eligibility for inclusion. Data will be pooled from eligible articles and the main outcome of recurrent cervical artery dissection at 5 years will be determined using quantitative analysis.Ethics and disseminationEthics approval is not necessary as no primary data are being collected. The information will be disseminated in the form of a systematic review article which will be submitted to a peer-reviewed medical journal.Prospero registration numberCRD42020166105.
| S-EPMC7488837 | biostudies-literature
Project description:ObjectiveTo investigate the prevalence of connective tissue abnormalities in patients with spontaneous cervical artery dissections (sCeAD).MethodsWe systematically assessed clinically detectable signs of connective tissue aberration in a series of consecutive patients with sCeAD and of age- and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) by a standard examination protocol including 68 items, and performed extensive molecular investigation for hereditary connective tissue disorders in all patients with sCeAD.ResultsThe study group included 84 patients with sCeAD (mean age, 44.5 ± 7.8 years; 66.7% men) and 84 patients with non-CeAD IS. None of the patients with sCeAD met clinical or molecular diagnostic criteria for established hereditary connective tissue disorder. Connective tissue abnormalities were detected more frequently in the group of patients with sCeAD than in the group of those with non-CeAD IS (mean number of pathologic findings, 4.5 ± 3.5 vs 1.9 ± 2.3; p < 0.001). Eighty-one patients (96.4%) in the sCeAD group had at least one detectable sign compared with 55 patients (66.7%) in the group with non-CeAD IS (p < 0.001). Skeletal, ocular, and skin abnormalities, as well as craniofacial dysmorphisms, were the clinical signs more strongly associated with sCeAD. Signs suggesting connective tissue abnormality were also more frequently represented in patients with sCeAD than in patients with traumatic CeAD (28.6%, p < 0.001; mean number of pathologic findings, 1.7 ± 3.7, p = 0.045).ConclusionsConnective tissue abnormalities are frequent in patients with sCeAD. This reinforces the hypothesis that systemic aberrations of the connective tissue might be implicated in the pathogenesis of the disease.
| S-EPMC4248452 | biostudies-literature
Project description:ObjectiveHead/neck pain is one of the primary symptoms associated with spontaneous cervical artery dissection. Still, data on pain quality, intensity, and long-term dynamics are scarce.MethodsSpontaneous cervical artery dissection subjects were included if mural hematoma was visualised through T1 fat-saturated MRI at baseline. All available medical records were evaluated and patients were invited to standardised clinical follow-up visits at least 1 year after the index event.ResultsIn total, 279 subjects were included in the ReSect-study with head/neck pain being the most frequent symptom of spontaneous cervical artery dissection (220 of 273, 80.6%). Pain was of pulling nature in 107 of 218 (49.1%), and extended to the neck area in 145 of 218 (66.5%). In those with prior headache history, pain was novel in quality in 75.4% (42 of 55). Median patient-reported pain intensity was 5 out of 10 with thunderclap-type headache being uncommon (12 of 218, 5.5%). Prior to hospital admission, head/neck pain rarely responded to self-medication (32 of 218, 14.7%). Characteristics did not differ between subjects with and without cerebral ischemia. Pain resolved completely in all subjects within a median of 13.5 days (IQR 12). Upon follow-up in 42 of 164 (25.6%) novel recurring headache occurred, heterogeneous in quality, localisation and intensity.ConclusionWe present an in-depth analysis of spontaneous cervical artery dissection-related head/neck pain characteristics and its long-term dynamics.
| S-EPMC9315176 | biostudies-literature