Restart or stop antithrombotics after intracerebral haemorrhage (ICH)?

Transcription

1 Restart or stop antithrombotics after intracerebral haemorrhage (ICH)? Rustam Al-Shahi Salman professor of clinical neurology & honorary consultant neurologist /bleedingstroke

2 My declarations Salary (paid to me) Editorial boards (paid to me) Research grants/awards/donations (paid to my employer)

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5 77 year-old woman Sudden aphasia, dysarthria, and right hemiparesis PMH Ischaemic stroke 2015 CLL, GORD, diverticular disease, osteoporosis, BCC etc Aspirin, lansoprazole, folic acid, bisoprolol Diagnostic CT 3-month MRI (GRE & FLAIR)

6 Her aspirin was discontinued What will you do when you see her in clinic? 1. Restart aspirin 2. Permanently discontinue aspirin 3. Leave it up to the general (family) practitioner 4. I m not sure

7 Why bother? Antithrombotic drugs are more common at ICH onset nowadays Antiplatelet drugs Anticoagulant drugs No antithrombotic drugs Antiplatelet drugs Anticoagulant drugs No antithrombotic drugs Lancet Neurology 2007;6:487-93

8 Why worry? Similar risks of recurrent ICH & ischaemic stroke after ICH in cohort studies Study Sample size Time (yrs) Recurrent ICH, %/year (95%CI) Ischaemic stroke, %/year (95%CI) Vermeer et al ( ) 1.4 ( ) Azarpazhooh et al ( ) 3.7 ( ) Yokota et al ( ) 4.0 ( ) Zia et al ( ) 6.8 ( ) JNNP 2014;85:660-7

9 But + =?

10 Before blaming anti-thrombotic drugs, reflect on major risk factors for ICH in case-control studies Lancet 2010;376:112-23

11 Aspirin wasn t associated with ICH in another case-control study Aspirin use ICH cases (n=331) Controls (n=331) Adjusted OR* (95%CI) Aspirin in past 2/52 55/300 58/ ( ) Aspirin dose in past 2/52: None 245/ /322 Less than alternate days 19/299 28/ ( ) 1,225mg/week 16/299 21/ ( ) >1,225mg/week 19/299 9/ ( ) * Adjusted for hypertension, serum cholesterol concentration, diabetes, previous cardiovascular disease, body mass index, exercise, alcohol intake, and smoking BMJ 1999;318:759-64

12 Aspirin wasn t associated with ICH in a big cohort study over ~5 years Aspirin use ICH cases (n=660) Controls (n=10,000) Adjusted RR* (95%CI) Current use in <7 days 312 4, ( ) Duration in current users: <1 year 87 1, ( ) 1-<5 years 122 1, ( ) 5 years ( ) 75mg 238 3, ( ) mg ( ) * Adjusted for age, sex, calendar year, number of GP visits, smoking, BMI, alcohol use, hypertension, AF, ischaemic stroke/tia, prior intracranial bleed, clopidogrel, warfarin Neurology 2017;89:1-8

13 Antiplatelet drugs don t significantly increase ICH risk in RCTs Outcome event Control (%/yr) Aspirin (%/yr) Absolute difference Event rate ratio (95%CI) Serious vascular event ( ) Ischaemic stroke ( ) Major coronary event ( ) Haemorrhagic stroke ( ) Lancet 2009;373:

14 No increase in ICH with aspirin after intracranial haemorrhage in cohort studies Study Patients Intervention / Comparator Outcome associations with aspirin use ICH Ischaemic stroke Acute coronary syndrome All serious vascular events Flynn et al Scotland PICH Aspirin 297 none NS NS NS NS Biffi et al USA Lobar CAA-ICH Aspirin 88 none NS NS NS NS Teo et al Hong Kong Antiplateletassociated ICH 37 Aspirin 72 none NS - NS - Chong et al Hong Kong PICH, SAH, SDH Aspirin 384 none NS NS = no significant association with aspirin use = significant increase with aspirin use = significant decrease with aspirin use Stroke 2010, Neurology 2010, Thromb Haemost 2012, World Neurosurg 2017

15 RCTs are needed 81-year-old woman with sudden aphasia PMH cognitive decline and TIAs Aspirin 75mg daily Aspirin withheld Stroke 2014;45:

16 2 cerebral microbleeds are associated with recurrent ICH CAA-unrelated ICH 2-4 microbleeds 5-10 microbleeds >10 microbleeds CAA-related ICH 2-4 microbleeds 5-10 microbleeds >10 microbleeds OR ICH more frequent with brain microbleeds Neurology 2017;89:820-9

17 So let s randomise! RCTs of antiplatelet drugs after ICH Acronym Sample size Contact RESTART 505 Rustam Al-Shahi Salman RESTART-Fr 13 Charlotte Cordonnier STATICH 0 Eivind Berge Cochrane Database Syst Rev 2017;5:CD012144

18 REstart or STop Antithrombotics Randomised Trial On antithrombotics for vaso-occlusive disease prevention + spontaneous ICH Pre-randomisation: brain MRI (optional sub-study) Randomisation (web-based) 1:1 360 START antiplatelet drugs* 360 AVOID antiplatelet drugs Follow-up for 2 years (central via GP, after local hospital discharge) * Aspirin or clopidogrel or dipyridamole

19 Apr Jul Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr 505 recruits at 124 sites Original grant target Actual recruitment extension ISRCTN

20 What about anticoagulants? 73 year-old man with hypertension, nonvalvular AF Taking warfarin Presents with alexia, dysphasia, nausea and headache CHA 2 DS 2 -VASc score = 2

21 Observational studies of OAC for AF after ICH Study Study design Antithrombotic drug use ICH (%/yr) IS (%/yr) Any SVE (%/yr) All hospitals in Denmark (Nielsen) 19 hospitals in Germany (Kuramatsu) Population of Taiwan (Chao) AF treated with OAC <6 months before intracranial haemorrhage Followed 1 year. AF and VKA-associated primary intracerebral haemorrhage Followed 1 year. AF, CHA 2 DS 2 -VASc 2, and a past history of intracranial haemorrhage Followed mean 3.3 years. 1,089 none antiplatelet OAC none warfarin ,211 none ,552 antiplatelet ,154 warfarin Circulation 2015, JAMA 2015, Circulation 2016

22 Start or STop Anticoagulants Randomised Trial Intracranial haemorrhage, atrial fibrillation, and CHA 2 DS 2 -VASc score 2 Pre-randomisation: brain MRI (optional sub-study) Randomisation (central) 1:1 START oral anticoagulation* AVOID oral anticoagulation Follow-up for 1 year (local hospital discharge, then central via GP and patient) * Direct / non-vitamin K OAC (NOAC/DOAC) or warfarin

23 So let s randomise! RCTs of anticoagulant drugs after ICH Acronym Sample size Contact APACHE-AF NASPAF-ICH SoSTART A 3 ICH STATICH 40 Karin Klijn & Bart van der Worp 3 Ashkan Shoamanesh 0 Rustam Al-Shahi Salman 0 Charlotte Cordonnier 0 Eivind Berge Cochrane Database Syst Rev 2017;5:CD012144

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