Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS)
T2 - a randomised trial
AU - Markus, Hugh S.
AU - Hayter, Elizabeth
AU - Levi, Christopher
AU - Feldman, Adina
AU - Venables, Graham
AU - Norris, John
AU - Emsley, Hedley
AU - CADISS trial investigators
N1 - Copyright © 2015 Markus et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
PY - 2015/4
Y1 - 2015/4
N2 - BACKGROUND: Extracranial carotid and vertebral artery dissection is an important cause of stroke, especially in young people. In some observational studies it has been associated with a high risk of recurrent stroke. Both antiplatelet drugs and anticoagulant drugs are used to reduce risk of stroke but whether one treatment strategy is more effective than the other is unknown. We compared their efficacy in the Cervical Artery Dissection in Stroke Study (CADISS), with the additional aim of establishing the true risk of recurrent stroke.METHODS: We did this randomised trial at hospitals with specialised stroke or neurology services (39 in the UK and seven in Australia). We included patients with extracranial carotid and vertebral dissection with onset of symptoms within the past 7 days. Patients were randomly assigned (1:1) by an automated telephone randomisation service to receive antiplatelet drugs or anticoagulant drugs (specific treatment decided by the local clinician) for 3 months. Patients and clinicians were not masked to allocation, but investigators assessing endpoints were. The primary endpoint was ipsilateral stroke or death in the intention-to-treat population. The trial was registered with EUDract (2006-002827-18) and ISRN (CTN44555237).FINDINGS: We enrolled 250 participants (118 carotid, 132 vertebral). Mean time to randomisation was 3·65 days (SD 1·91). The major presenting symptoms were stroke or transient ischaemic attack (n=224) and local symptoms (headache, neck pain, or Horner's syndrome; n=26). 126 participants were assigned to antiplatelet treatment versus 124 to anticoagulant treatment. Overall, four (2%) of 250 patients had stroke recurrence (all ipsilateral). Stroke or death occurred in three (2%) of 126 patients versus one (1%) of 124 (odds ratio [OR] 0·335, 95% CI 0·006-4·233; p=0·63). There were no deaths, but one major bleeding (subarachnoid haemorrhage) in the anticoagulant group. Central review of imaging failed to confirm dissection in 52 patients. Preplanned per-protocol analysis excluding these patients showed stroke or death in three (3%) of 101 patients in the antiplatelet group versus one (1%) of 96 patients in the anticoagulant group (OR 0·346, 95% CI 0·006-4·390; p=0·66).INTERPRETATION: We found no difference in efficacy of antiplatelet and anticoagulant drugs at preventing stroke and death in patients with symptomatic carotid and vertebral artery dissection but stroke was rare in both groups, and much rarer than reported in some observational studies. Diagnosis of dissection was not confirmed after review in many cases, suggesting that radiographic criteria are not always correctly applied in routine clinical practice.FUNDING: Stroke Association.
AB - BACKGROUND: Extracranial carotid and vertebral artery dissection is an important cause of stroke, especially in young people. In some observational studies it has been associated with a high risk of recurrent stroke. Both antiplatelet drugs and anticoagulant drugs are used to reduce risk of stroke but whether one treatment strategy is more effective than the other is unknown. We compared their efficacy in the Cervical Artery Dissection in Stroke Study (CADISS), with the additional aim of establishing the true risk of recurrent stroke.METHODS: We did this randomised trial at hospitals with specialised stroke or neurology services (39 in the UK and seven in Australia). We included patients with extracranial carotid and vertebral dissection with onset of symptoms within the past 7 days. Patients were randomly assigned (1:1) by an automated telephone randomisation service to receive antiplatelet drugs or anticoagulant drugs (specific treatment decided by the local clinician) for 3 months. Patients and clinicians were not masked to allocation, but investigators assessing endpoints were. The primary endpoint was ipsilateral stroke or death in the intention-to-treat population. The trial was registered with EUDract (2006-002827-18) and ISRN (CTN44555237).FINDINGS: We enrolled 250 participants (118 carotid, 132 vertebral). Mean time to randomisation was 3·65 days (SD 1·91). The major presenting symptoms were stroke or transient ischaemic attack (n=224) and local symptoms (headache, neck pain, or Horner's syndrome; n=26). 126 participants were assigned to antiplatelet treatment versus 124 to anticoagulant treatment. Overall, four (2%) of 250 patients had stroke recurrence (all ipsilateral). Stroke or death occurred in three (2%) of 126 patients versus one (1%) of 124 (odds ratio [OR] 0·335, 95% CI 0·006-4·233; p=0·63). There were no deaths, but one major bleeding (subarachnoid haemorrhage) in the anticoagulant group. Central review of imaging failed to confirm dissection in 52 patients. Preplanned per-protocol analysis excluding these patients showed stroke or death in three (3%) of 101 patients in the antiplatelet group versus one (1%) of 96 patients in the anticoagulant group (OR 0·346, 95% CI 0·006-4·390; p=0·66).INTERPRETATION: We found no difference in efficacy of antiplatelet and anticoagulant drugs at preventing stroke and death in patients with symptomatic carotid and vertebral artery dissection but stroke was rare in both groups, and much rarer than reported in some observational studies. Diagnosis of dissection was not confirmed after review in many cases, suggesting that radiographic criteria are not always correctly applied in routine clinical practice.FUNDING: Stroke Association.
KW - Adult
KW - Aged
KW - Aneurysm, Dissecting
KW - Anticoagulants
KW - Arteries
KW - Carotid Artery, Internal, Dissection
KW - Female
KW - Humans
KW - Ischemic Attack, Transient
KW - Male
KW - Middle Aged
KW - Odds Ratio
KW - Platelet Aggregation Inhibitors
KW - Spine
KW - Stroke
KW - Subarachnoid Hemorrhage
KW - Comparative Study
KW - Journal Article
KW - Randomized Controlled Trial
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/S1474-4422(15)70018-9
DO - 10.1016/S1474-4422(15)70018-9
M3 - Journal article
C2 - 25684164
VL - 14
SP - 361
EP - 367
JO - Lancet Neurology
JF - Lancet Neurology
SN - 1474-4422
IS - 4
ER -