Updates from 2017 International Stroke Conferences Ravi Menon, MD Swedish Neuroscience Institute May 11, 2017 Seattle, WA 1
Disclosures No relevant financial disclosures Clinical trial involvement: Former site PI SOCRATES; sub-investigator for PRISMS, icas; Blinded examiner REFLECT AAN Stroke Quality Working Group Will discuss non-fda approved use/clinical trial study of cilostazol, head position, imaging, ticagrelor, anticoagulation 2
Objectives: Discuss recent completed/pending trials in ischemic stroke diagnosis and treatment involving interventions at the bedside and in the angiography suite Evaluate recent intracerebral hemorrhage trials utilizing imaging selection and coagulant interventions Analyze new research involving the use of antithrombotics in the setting of ischemic stroke and prior intracerebral hemorrhage 3
Objectives: Discuss recent completed/pending trials in ischemic stroke diagnosis and treatment involving interventions at the bedside and in the angiography suite Evaluate recent intracerebral hemorrhage trials utilizing imaging selection and coagulant interventions Analyze new research involving the use of antithrombotics in the setting of ischemic stroke and prior intracerebral hemorrhage 4
International Stroke Conference (AHA/ASA) My bottom line is that you can only attend this conference if you are on antidepressants. Basically, almost all of the presented studies were negative. This is partly due to the medical problem being studied, but many of these trials also had serious design problems or were underpowered. Flawed Studies Define This Year's International Stroke Conference Hans-Christoph Diener, MD, PhD COMMENTARY Medscape 5
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AHA ischemic stroke guidelines In nonhypoxic patients able to tolerate lying flat, a supine position is recommended patients at risk for airway obstruction or aspiration and those with suspected elevated ICP should have the head of the bed elevated 15 to 30 The ideal position of a stroke patient to optimize these parameters, however, is unknown, and the clinician must balance often cometing interests, as well as patient tolerance 7
HeadPoST: Head Position in Stroke Trial Randomized to two head positions after acute ischemic stroke OR ICH Head up >=30 vs Head flat Interventionw/in first 24 hrs Design: international, multicenter, cluster crossover clinical trial; central blind telephone outcome assessment 8
Strengths: >11,000 patients from 114 hospitals in 9 countries Simple, pragmatic intervention- largest randomized crossover Nursing care trial Central randomization and rigorous outcome assessment Pre-specified statistical analysis Good adherence to protocol and intervention Weaknesses Population <1/3 large volume/severe; although low NIHSS more common globally, overall wrong population (median NIHSS 4) Patients presented late Uncertainty optimal head position; variable intervention (nonmechanical bed/ pillows); duration intervention Bias/confounding Clinical scenario challenging/ impact practice- severe/icp cases 9
Take Home Message No difference in effects on disability outcome Positioning is safe - no differential SAEs or pneumonia (design limitations) Primary outcome: 90 day mrs : No difference between the head-up or head-down position No difference subgroups: age/demographics, stroke-type/anatomical region or time from symptom onset Patients: Acute stroke, uncertainty principle SAEs including pneumonia no difference Lying flat is uncomfortable Subgroups = No clear benefits (or harms): Time from onset of symptoms Initial stroke severity Age Region (resource poor- lay flat / pillows) AIS including subtype of ischemic stroke vs. ICH 10
http://www.pablopicasso.org/three-musicians.jsp 11
Prior ICH: OK for antithrombotics? ICH guidelines suggest: Anticoagulation after nonlobar ICH and antiplatelet monotherapy after any ICH might be considered, particularly when there are strong indications for these agents (Class IIb; Level of Evidence B) Cilostazol Versus Aspirin in Ischemic Stroke Patients With Intracerebral Hemorrhage or Multiple Microbleeds PreventIon of CArdiovascular events in ischemic Stroke patients with high risk of cerebral hemorrhage (PICASSO) study: Aims: investigate the safety and efficacy of cilostazol in ischemic stroke patients prone for cerebral hemorrhage. 12
PreventIon of CArdiovascular events in ischemic Stroke patients with high risk of cerebral hemorrhage (PICASSO) study Kwon, S. et. al. Multicenter (SKorea, China, Phillipines) Randomized control trial of ischemic stroke patients with high-risk cerebral hemorrhage; history or an imaging finding of intracerebral hemorrhage or multiple microbleeds Results: Among 1512 participants 755 Cilostazol and 757 ASA Mean follow-up of 2.0 years Cilostazol (200mg/day) or aspirin (100mg/day) Co-primary endpoints of safety and efficacy: Time to event of ICH (spontaneous IPH/SAH) Composite of CVA, MI, Vascular death Non-inferiority test for efficacy / Superiority test for safety 13
Cilostazol Pluripotent effect Inhibit SMC proliferation, induce vasodilation, reduce inflammation Kwon, S. ISC 2017 14
PICASSO Results CILOSTAZOL NOT INFERIOR TO ASPIRIN Composite Vascular Event rate 63 events (4.27/100 person-year) vs ASA 80 events (5.33/100 person-year) Safety outcome, 8 events (1.1%, 0.61/100 person-year) Cilostazol versus ASA (2.1%, 1.20/person-year) in the aspirin group (p=0.0916) LESS STROKE w/cilostazol (48 events, 3.25/100 person-year) vs ASA (73 events, 4.86/100 person-year; p=0.0273) MORE MYOCARDIAL INFARCTION w/cilostazol (9 events, 0.61/100 person-year) VS ASA (2 events, 0.13/100 person-year; p=0.0319) OVERALL SAME BLEEDING - NOT SUPERIOR BLEEDING RISK w/cilostazol vs ASA trend toward less ICH w/cilostazol 15
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PICASSO Message Cilostazol can be used for secondary stroke prevention Decreased stroke/vascular events in comparison to aspirin Weigh risk myocardial infarction carefully Individual patient risk:benefit East Asian experience safety West PAD; > experience 17
ICH Guidelines, AHA 2015 Anticoagulation after nonlobar ICH and antiplatelet monotherapy after any ICH might be considered, particularly when there are strong indications for these agents (Class IIb; Level of Evidence B) The optimal timing to resume oral anticoagulation after anticoagulantrelated ICH is uncertain. Avoidance of oral anticoagulation for at least 4 weeks, in patients without mechanical heart valves, might decrease the risk of ICH recurrence (Class IIb; Level of Evidence B) If indicated, aspirin monotherapy can probably be restarted in the days after ICH, although the optimal timing is uncertain (Class IIa; Level of Evidence B) The usefulness of dabigatran, rivaroxaban, or apixaban in patients with atrial fibrillation and past ICH to decrease the risk of recurrence is uncertain (Class IIb; Level of Evidence C) 18
ICH Risk:Beneft 2003 study model ICH Afib Lobar vs Deep ICH? Anticoagulate Lobar ICH= NO Deep ICH +Afib = NO Deep ICH + >high-risk cva Or low risk ICH = Maybe 19
Resumption of Oral Anticoagulation after Intracerebral Hemorrhage is Associated with Decreased Mortality and Favorable Functional Outcome Biffi, A. et. al. Overall Study Goal: Determine whether OAT resumption after Lobar vs. Non-lobar ICH is associated with long-term outcome 20
Background ICH location (lobar vs. non-lobar): provides information on underlying etiology (CAA vs. HTN) associated with different ICH recurrence rates The impact of ICH location on OAT resumption after ICH has never been systematically investigated Prior studies of OAT resumption after ICH focused on mortality/stroke recurrence, neglecting functional outcome Impact of ICH location on functional outcome after OAT resumption has not been explored. 21
Methods Meta-analysis of individual-level data from 3 ICH studies: RETRACE study (multi-center), Germany (n=542) MGH longitudinal ICH study, Boston USA (n=268) ERICH study (multi-center), USA (n=217) Inclusion Criteria: Acute ICH (CT-confirmed) Age 18 years or older at time of ICH No history of prior ICH (before index event) Event on (OAT) with VKA/NOAC for prevention of cardioembolic stroke due to non-valvular atrial fibrillation Examined association of OAT at one year from index ICH with: Mortality / favorable functional outcome (mrs 0-3) Recurrent ICH and ischemic stroke 22
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Outcomes at 1 year post-oat resumption (both lobar and non-lobar ICH) Decreased mortality risk Improved functional outcome Decreased ischemic stroke risk OAT resumption after CAA-related ICH (per Boston criteria) was associated with decreased mortality and improved outcome Support conducting clinical trials of OAT resumption and outcome after primary ICH 25
Limitations Observational study Only 1 year followup Very few patients on NOAC 26
References AHA/ASA Guidelines for the Management of Spontaneous Intracerebral Hemorrhage Hemphill, C et. al. Stroke July 2015 AHA/ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Jauch EC, et al. Stroke 2013; 44: 870-947 Resumption of Oral Anticoagulation after Intracerebral Hemorrhage is Associated with Decreased Mortality and Favorable Functional Outcome Thursday. Biffi, A. et. al. AHA/ASA International Stroke Conference February 23, 2017 Cilostazol versus Aspirin in Ischemic Stroke Patients with Cerebral Macroor Micro-Hemorrhage Kwon, S. et. al. AHA/ASA International Stroke Conference February 23, 2017 HeadPoST: Head Position in Stroke Trial. Anderson CS, et. al. AHA/ASA International Stroke Conference February 22, 2017 27