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Antithrombotic management in the setting of Intracerebral Hemorrhage

Antithrombotic management in the setting of Intracerebral Hemorrhage. Girish Hiremath , MD, FAANS. Introduction. Spontaneous ICH ( sICH ) 15% of all acute strokes Deadliest stroke subtype 1 month mortality of 40% At 1 year, 75% die or are severely disabled

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Antithrombotic management in the setting of Intracerebral Hemorrhage

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  1. Antithrombotic management in the setting of Intracerebral Hemorrhage GirishHiremath, MD, FAANS

  2. Introduction • Spontaneous ICH (sICH) • 15% of all acute strokes • Deadliest stroke subtype • 1 month mortality of 40% • At 1 year, 75% die or are severely disabled • Initial hematoma volume remains strongest predictor of 30-day mortality and functional outcome • Only modifiable predictor of outcome Qureshi, Lancet 2009 Van Asch, Lancet Neurol 2010 Broderick, Stroke 1993

  3. Hematoma Volume • Larger more likely to expand • Early presentation after symptom onset • Anticoagulation use • Presence of APOE ε2 allele • CTA spot sign • Newer marker for hematoma expansion • Poor functional outcome, death • Low sensitivity Cucchiara, Stroke 2008 Broderick, Stroke 2007 Delgado, Stroke 2010 Brouwers, Stroke 2012

  4. Should patients be anticoagulated after a history of ICH? • Dilemma: pt with past ICH develops clear indication for A/C such as Afib • Risk of thromboembolism is 4.5% with Afib • Efficacy of warfarin for stroke prevention: 68% • Decision analysis models (no RCT’s) • Assumptions: • Relative risk of bleeding on ASA in this cohort—SDH = 2.0 • Relative risk of bleeding on A/C—ICH = 2.0; SDH = 4.0 • For 1000 patients with lobar ICH, A/C would result in 31 fewer thromboembolic events, but 150 additional ICH’s • Conclusions: • A/C not indicated after lobar ICH • A/C resumption unclear after deep ICH (probably no unless very high risk of ischemic stroke) • ASA indicated only if RR for deep ICH is < 1.3 and for lobar ICH < 1.04 Eckman, Stroke 2003

  5. If no anticoagulation, is antiplatelet better than no treatment at all?

  6. Case Example • 72 year old white man presents with expressive aphasia, headache, declining mental status • Likely spontaneous—no specific hx of trauma • On ASA/PLAVIX for CAD • L Acute SDH (2cm) with 1cm MLS; L inferior frontal contusion/ICH • Underwent platelet tx, emergent craniotomy, evacuation of SDH

  7. POD #1

  8. POD 2—more lethargic, worse expressive aphasia (cont’d plttx); CT shows recurrent L frontal ICH, SDH, MLS Redo Urgent Craniotomy…

  9. POD 4: doing well clinically, but draining scalp incision

  10. 3 wks later—wound infection/infected bone flap—wound washout, craniectomy

  11. ASA stopped (10 days prior), underwent Cranioplasty 5 months later with postop EDH (developed 12h after surgery with presentation of weak RUE, expressive aphasia)--underwent take back for evacuation

  12. Eventually did well—sutures out… (5 surgeries later)

  13. Story doesn’t end… • 1 week later: • Admitted to OSH with massive MI, resulting in resumption of ASA/PLAVIX…

  14. Antiplatelet use and ICH • 22071 male physicians (aged 40-84) randomly assigned to 325mg ASA or placebo qOD • At 5 yrs: • ASA use was associated with 2.14 X higher risk of hemorrhagic stroke • Swedish Aspirin Low-dose Trial (SALT) • 1360 pts with hx of TIA/minor stroke randomly assigned to 75mg/d of ASA or placebo for 2.8 yrs • ASA use associated with 2.78 X higher risk of hemorrhagic stroke Steering Committee of the Physicians’ Health Study Research Group; NEJM 1989 SALT Collaborative Group; Lancet 1991

  15. Antiplatelet use and ICH… • Meta-analysis of 16 RCT’s on ASA use • International study of 55462 participants • RR reduction of MI with ASA • RR reduction of ischemic stroke with ASA • RR increase in hemorrhagic stroke with ASA (84% increased RR) • (all three were significant at P <.001) He et al, JAMA 1998

  16. What about Recurrent ICH? • Meta-analysis of 1880 ICH survivors between 1982 and 2000 • Mean age 65 • Mean f/u: 3.4 yrs from index ICH • Stroke recurrence: • 59% hemorrhagic • 26% ischemic • Recurrent ICH occurs at 2X the rate of ischemic stroke in survivors of primary ICH • 2.4% per year rate of recurrent ICH • Higher risk with lobar hemorrhage Bailey et al; Neurology 2001

  17. Resumption of AP following ICH?Viswanathan et al • 207 patients with index ICH • Lobar • Deep • AP prescribed in 22% of survivors • Avg of 5.4 months after index ICH • Most commonly for ischemic cardiovascular dz • ICH recurred in 22% of survivors • No increase in risk of recurrent ICH with ASA resumption • (p = 0.73) • ICH location not factor (lobar vs. deep) • Limitations: • Selection bias (pts felt to be high risk for repeated ICH likely did not have AP resumption) • Resumption of ASAdid NOT significantly improve cardiovasc morbidity (p =.75) • Small sample size (only 46 pts had recurrent ICH) Viswanathan et al; Neurology 2006 Donnan and Ly; Neurology 2006

  18. Resumption of AP following ICHFlynn et al • Observational, Community-based study in Scotland • 417 pts with ICH • 120 prescribed Antiplatelet medications (28.8%) • Median time from d/c to AP use was 14.8 months • 40 ischemic strokes/MI • 14 recurrent ICH • Study found no association between AP use and recurrent ICH • Limitations: • Small sample size • Selection bias • ? Delay in resuming of AP to 14.8 months after index ICH Flynn et al; Stroke 2010

  19. In summary: When to resume ASA after ICH? • There is no good answer! • No good literature to guide the neurosurgeon (or neurologist) • There is not likely to be a RCT • In general, it is prudent to wait at least one month • Must be made on a case-by-case basis • NOT by a “protocol-driven” approach

  20. DVT Prophylaxis in the setting of ICH VTE is frequent in pts with ischemic and hemorrhagic stroke 5% of early deaths following stroke attributed to PE

  21. VTE in elective NS patients • Incidence of DVT in untreated NS pts: 18-50% • Multiple studies have shown the safety of pharmacological DVT prophylaxis in the setting of elective NS • In 555 pts undergoing elective NS procedures, LDSQUFH: • Reduced DVT by 43% (measured by U/S) • Risk reduction NOT assoc with incr hemorrhage • Did not alter the rate of PE • No correlation between DVT and PE • (In general, 30% of pts with acute PE have no LE DVT) • PE directly related only to length of procedure • (? Lack of statistical power) Khaldi et al; J Neurosurg 2011; Agnelli et al; NEJM 1998; Geerts; Chest 2001 Cage et al; J Neurooncology 2009 ChibbaroSurgNeurol 2008

  22. Mechanical Prophylaxis in sICH works! • 133/151 evaluated at day 10 after ICH • Endpoints: a/symptomatic DVT/PE • 14 asymptomatic DVT’s identified • 3 in ES only group • 11 in ES + IPC group • IPC combined with graded ES reduced the risk of asymptomatic DVT at day 10 following ICH by 71% compared with ES alone. Lacut et al; Neurology 2005 (VICTORIAh study)

  23. Anticoagulants in prevention of VTE in sICH • Meta-analysis of RCT’s of prophylactic use (within 6 days) of SQ • UFH • LMWH • Heparinoids • Endpoints: • A/symptomatic DVT • A/symptomatic PE • Death • A/symptomatic hematoma enlargement Paciaroni et al; J Thrombosis and Haemostasis 2011

  24. Anticoagulants in prevention of VTE in sICH • 4 studies included • 2 used UFH • 2 used LMWH • Results: • A/C resulted in sig reduction in: • PE • A/C resulted in NON-sig • Reduction in mortality • Reduction in DVT • Hematoma enlargement Paciaroni et al; J Thrombosis and Haemostasis 2011

  25. Other Studies… 97 patients with sICH were all given LMWH in the form of Enoxaparin or Dalteparin 2 patients developed moderate enlargement of hematoma No fatal PE’s Limitations: Non-randomized; no control group; limited sample size Kiphuth et al; Cerebrovasc Dis 2009

  26. Anticoagulants in prevention of VTE in traumatic ICH • 2 cohorts of 107, 129 pts each with tICH (1 served as a historic control) • Both groups tx with SCD’s • Following stable Head CT, 1 group underwent tx with either LMWH (Lovenox 30mg BID or SQUFH 5000 TID) • Group A (no tx): DVT rate was 5.6% • Group B (tx): DVT rate was 0% • No progression of ICH • NO sig difference in rate of PE (P = 0.179) with trend towards lower rate of PE in pts undergoing pharmacological prophylaxis Farooqui et al; J Neurosurg 2013

  27. Summary: Pharmacological DVT prophylaxis in the setting of ICH • In general, rates of DVT and PE are reduced with the use of pharmacological prophylaxis in the setting of sICH and tICH • There is probably no significant hematoma enlargement with the use of such prophylaxis • However, many studies show no significant correlation between DVT and PE; some show no significant reduction in rate of PE with pharm prophylaxis • The idea that mortality is reduced with the use of pharmacological DVT prophylaxis is yet to be proven

  28. Thank You

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