. 8. Pharmacological treatment in acute stroke 8.3 Antiplatelet and anticoagulant treatment in stroke due to arterial dissection

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1 . 8. Pharmacological treatment in acute stroke 8.3 Antiplatelet and anticoagulant treatment in stroke due to arterial dissection Reference Evidence Tables PHARM4 What is the safety and efficacy of anticoagulants versus antiplatelets for the treatment of patients with acute arterial dissection Lyrer P, Engelter S. Antithrombotic drugs for carotid artery dissection. Cochrane Database of Systematic Reviews. 2003; Ref ID: 1446 Study type Evidence level Cochrane systematic review 3 (no RCTs or case controlled series identified) Number of patients 26 studies (N=327) (inclusion criteria of 4 or more eligible patients) Patient characteristics Patients with extracranial internal carotid dissection Intervention Comparison Length of follow-up Outcome measures Antiplatelets (either compared with anticoagulants or compared with other treatments) (either compared with antiplatelets or compared with other treatments) Not reported Death Disability First or recurrent stroke Intracranial haemorrhage Source of funding Authors employed by Eli Lilly *Death (N=327 based on 26 case series) Two of 109 patients (1.8%) treated with antiplatelet drugs were reported dead, and 4 of 218 (1.8%) treated with anticoagulants, respectively (Peto odds ratio (OR) 1.59, 95%CI 0.22 to 11.59; NS) *Death from all causes or disabled (N=178 based on 20 case series) 14 of 59 patients (23.7%) treated with antiplatelet drugs met the criteria, compared to 17 of 119 (14.3%) patients treated with anticoagulants. The difference was not significant (OR 1.94; 95%CI 0.76 to 4.91; NS) Other studies on antithrombotic treatment 48 patients had antiplatelets of whom none were dead and 10 were reported disabled. There were a further 196 patients who had anticoagulants of these, seven were reported dead and 34 disabled. From all 64 studies (all studies reporting on antithrombotic treatment), 91 patients had no treatment. From these, 23 (25%) patients were reported dead and 13 (14%) disabled. *First or recurrent stroke

2 Of the 157 patients given antiplatelets, six (3.8%) had first or recurrent stroke. Of 414 patients given anticoagulants 5 (1.2%) were reported to have a first or recurrent stroke on treatment. *Intracranial haemorrhage Two (1.5%) patients on antiplatelet therapy and two (1.5%) patients on anticoagulant therapy had an intracranial haemorrhage whilst on treatment. Arauz A, Hoyos L, Espinoza C et al. Sequential observational N=130 (over a ten yr period) Angiographically proven dissection of cervical arteries Aspirin (heparin Dissection of cervical study 3 oral anticoagulants arteries: Long-term Patient population: Mean 35.4 yrs and CAD N=44 for 3-6 months) 50% male. follow-up study of 130 VAD N=38 CAD N=14 consecutive cases.[see Carotid artery dissection (N=58): comment]. Dissection type n (%): nontraumatic 39 VAD N=34 Cerebrovascular (67%), minor trauma 13 (22%), Major Diseases. 2006; 22(2- trauma 16 (10%) 3): Ref ID: 1607 Vertebral artery dissection (N=72) Dissection type n (%): Nontraumatic 46 (64%), minor trauma 20 (28%), major trauma 6 (8%) Death Modified Rankin Scale (mrs) Recanalisation Recurrent stroke Median 19 months (range 6 to 120 months) None reported *Death Modified Rankin Scale 0-2 on admission: CAD 9 (16%) and VAD 38 (53%) (p=0.0001) For CAD, 4 (9%) aspirin-treated patients died compared to none treated with anticoagulants For VAD, there were no deaths in the aspirin or anticoagulant groups. *Modified Rankin Scale For CAD, there were no statistically significant differences between the number of aspirin-treated and anticoagulant-treated patients with a mrs 0-2 (11 (24%) vs 5 (39%), respectively; NS) or with a mrs 3 (34 (76%) vs 8 (62%), respectively; NS). For VAD, there were no statistically significant differences in the number of patients on aspirin compared with anticoagulants with a mrs 0-2 (27 (71%) vs 29 (85%), respectively; NS) or 3 (11 (30%) vs 5/ (15%), respectively; NS). *Recanalisation For CAD, there was no statistically significant difference in the recanalisation rates between the aspirin and anticoagulant therapy treated patients (Complete 5 (11%) vs 3 (23%), respectively; NS) (Partial 12 (27%) vs 4 (31%); NS).

3 For VAD, there was a statistically significant difference in favour of anticoagulant therapy compared with aspirin on the number of patients with complete recanalisation 17 (50%) vs 9 (24%), respectively; p=0.02). There was no statistically significant differences between the aspirin and anticoagulant treated patients on the number with partial recanalisation (15/38 (40%) vs 7/34 (21%), respectively; p=0.08). *Recurrent stroke For CAD, there was no statistically significant differences between the number of recurrent strokes for patients treated with aspirin compared with anticoagulant therapy (3/44 (7%) vs 2/14 (14%), respectively; NS). For VAD, there was no statistically significant difference between aspirin and anticoagulant treated patients on the number of recurrent strokes (0/38 vs 1/34 patient, respectively; NS). Desfontaines P, Despland PA. case review 3 N=60 Patients with dissection of the Aspirin N=18 (aspirin Anticoagulant therapy N=34 Recanalisation Mean 37.5 months None reported Dissection of the internal carotid artery group) internal carotid artery: (angiography I.V heparin for 1 week confirmed) plus an oral anticoagulant Aetiology, agent (acenocounarol) symptomatology, Patient population: N=27 (heparin group) clinical and 28/60 male, mean neurosonological age 43.4 yrs (range Oral anticoagulant follow-up, and treatment in 60 consecutive cases. 13 to 63 yrs), 10/60 traumatic origin, 22/60 smokers, 9/60 therapy only N=3 (oral anticoagulation group) Acta Neurologica hypertension, focal Duration of therapy range Belgica. 1995; cerebral ischaemic 1 month to 12 months symptoms in 52/60 95(4): Ref ID: (80%) patients 235 (stroke 41/60 (68%), TIA 11/60 (18%). Of the 41 cases of internal carotid dissection associated stroke the majority involved the superficial middle cerebral artery (MCA) 12/41, deep MCA 8/41 or the total MCA 12/41

4 *Recanalisation rate Among the cases with stenotic or occlusive dissection, 21/29 (72.4%) were completely or partially recanalised. This compared with 16/24 (66.6%) patients who did not receive anticoagulant therapy (N=18 antiplatelets therapy and N=6 no specific treatment). There was no statistically significant difference between the recanalisation rate in those patients treated with anticoagulants compared with those who did not receive anticoagulation. Josien E. Extracranial vertebral artery dissection: Nine cases. Journal of Neurology. 1992; 239(6): Ref ID: 240 case review 3- N=9 Patients with extracranial vertebral artery dissection N=5 history of trivial trauma and N=4 spontaneous 66% male Age range: yrs Heparin (N=6) Individual patient data: 1) for two months aspirin 500 2) Heparin for 3 months followed by aspirin ) for 3 months aspirin 4) Aspirin 300 5) Heparin ventricular drainage 6) Aspirin or ticlopidine (N=3) Approximate range 2 months to 3 yrs 9 months Death/ recovery None reported

5 for 5 mths ticlopidine 500 7) Ticlopidine 500 8) Ticlopidine 500 9) Heparin 2 mths ticlopidine 500 *Death 1) Good recovery 2) Good recovery (tingling in arm, trunk and leg) 3) At 8 months aspirin stopped and experienced hypaesthesia and aspirin reintroduced (no further symptoms) 4) After 2 mths aspirin stopped but patient experienced dysmetria and incoordination. Restarted aspirin with no further symptoms 5) Dysmetria and ataxic gait 6) Mild hypotonia 7) Good recovery 8) Mild sensory impairment 9) Mild sensory impairment Savitz SI, Ronthal M, Caplan LR. Vertebral artery compression of the medulla. Archives of Neurology. 2006; 63(2): Ref ID: 25 case review 3-1) Aspirin. Tinnitus persists 2) Aspirin plus dipyridamole. No episodes in one year 3) Warfarin sodium. No episodes in one year 4) Aspirin. Significant improvement at 3 yrs N=8 (2 cases not reported due to surgical treatment and 1 treatment with analgesa) Patients with vertebral artery decompression of the medulla Patient population: age range 34 to 79 yrs. 3/6 males Antiplatelets N=4 aspirin N=1 Aspirin plus dipyridamole warfarin sodium N=1 Four years Recovery American Heart Association

6 5) Aspirin. No further deficits and one year 6) Aspirin. No further episodes in 4 yrs Han DH, Kwon OK, Oh CW. Clinical characteristics of vertebrobasilar artery dissection. Neurologia Medico-Chirurgica. 1998; 38 Suppl:107-13, 1998.: Ref ID: 386 case review 3- *Recovery All patients made an excellent recovery N=16 (N=7 presenting ischaemic symptoms reported here 9/16 subarachnoid haemorrhage) Patients with vertebrobasilar artery dissection Patient population: age range 15 to 58 yrs, 100% male Location of dissection: N=3 intracranial, N=2 extracranial and N=1 combined. Two patient excluded from outcome analysis (one patient with a carotid and vertebral artery dissection and one patient treated surgically) Anticoagulation N=2 Antiplatelet N=3 Recovery Range 8 to 276 months (for both SAH and ischeamic groups) Seoul National University and Seoul University Hospital