Stroke prophylaxis in an atrial fibrillation patient with chronic subdural hematoma – a double-edged sword Adam Mah, LMPS resident SPH/LGH Pod October 12 th , 2017 1
Learning objectives • Critically appraise the literature for OAC for patients with history of chronic subdural hematoma and atrial fibrillation (AF) • Weigh the benefits and risks of OAC in a patient with non-valvular A-fib and history of chronic subdural hematoma • Compare and contrast anticoagulation strategies for an inpatient with AF and history of chronic subdural hematoma 2
BW, 87 yo female admitted Sept 20 th to PIMS, ID transferred to CTU on Sept 26 th Back pain C/C Slipped and fell while using walker, found down HPI but conscious by son in bathroom PMHx - TIA (2008) - CAD - Hypothyroidism - Paroxysmal AF - COPD - Chronic constipation - Recurrent falls, last 2016 - HTN - Chronic subdural hematoma (~2008) - Pacemaker for 2 nd degree heart block Non-contributory for CV risk and osteoporosis FHx Lives in residential care, no smoking, no EtOH, SHx no illicits 3
Vitals BP 160/80, HR 70, RR 20 (90% 2L NP), temp not documented now RR 16 saturating 94% on RA CNS/Psyc AAOx3, GCS 15 delirious last HS, not easily rousable HEENT Pt refused full exam in ED Resp Chest clear to ascultation, no wheezes CV Pt refused full exam in ED. C HA D S2 = 4 GI Exam normal GU JVP not observed. No CVA tenderness Endo Not thirsty; A1c 5.6% (Sept 20) Heme No bruising, no hemoptysis or hematemesis MSK 7-9/10 pain to lumbar spine region (L3 to L4) Derm Unremarkable Allergies NKDA 4
Labs and diagnostics • Admission (current) – Na 140 (133), K 4.6 (4.2), SCr 104 (118), eGFR 42 (36), CrCl 30 (27) – INR 2.7 (1.2), albumin 32 (24), lactate 0.8 – NT-pro-BNP 3155, troponin 39, QTc 607 ms – TSH 0.31, A1c 5.6, random BG 6.5 • CT head : chronic subdural hematoma that is “stable and hasn’t grown”, no acute changes. CT spine : compression fracture • Dx: vertebral fracture secondary to mechanical fall 5
Held home Continued home medications medications Warfarin 4 mg PO daily Melatonin 3-6 mg PO 2 hrs before HS Amlodipine 2.5 mg PO Vitamin D 10 000 units PO daily weekly on Wednesdays Perindopril 2 mg PO daily L-thyroxine 137 mcg PO daily 6
Medications in hospital Sufentanil 12.5-25 mcg SL/SC 30 Ipratropium 0.5 mg nebs QID and q4h PRN mins before turns (max 4 Salbutamol 2.5 mg nebs QID and q4h PRN doses/day) Ca carbonate 1250 mg PO daily with food PEG 17 g PO daily Lactulose 30 mL PO daily Bisacodyl 10 mg PO daily HS Sennosides 8.6-17.2 mg PO HS PRN Hydromorphone 0.25 mg PO BID Acetaminophen 975 mg PO/PR QID ASA 81 mg PO/325 mg PR daily Atorvastatin 80 mg PO daily Captopril 12.5-25 mg SL q30min PRN SBP >220 7
DTPs – BW is… 1. At risk of recurrent cardiogenic ischemic stroke secondary to not receiving anticoagulation 2. At risk of VTE secondary to not receiving anticoagulation prophylaxis while in hospital 3. At risk of recurrent ischemic stroke secondary to not receiving antihypertensive therapy 4. At risk of barrier to discharge secondary to receiving nebulized ipratropium 5. At risk of barrier to discharge secondary to receiving nebulized salbutamol 8
Goals of therapy • Minimize risk of cardioembolic stroke • Minimize expansion of chronic subdural hematoma • Avoid neurological sequelae • Minimize adverse drug reactions 9
Where does a subdural hematoma (SDH) occur? http://www.primehealthchannel.com/wp-content/uploads/2011/02/Subdural-Hematoma-photos.jpg 10
Are all ICHs made equal? • SDH = Usually from head injury, mix of serous fluid and clotted blood 1 • Lobar ICH = Higher risk of re-bleed on anticoagulants 2 • Symptoms = decreasing cognition, headaches 1 • As time progresses, risk of clot goes up and risk of bleed goes down 2 11
Guidelines for ICH and resumption of anticoagulation • AHA/ASA 3 : After non-lobar ICH, may be considered if “strong indication” – Avoid anticoagulants for >4 weeks • Canada 4 : Decision whether to restart on “case - by- case” basis. Evidence unclear regarding timing • ESO (Europe) 5 : “In the absence of RCTs…cannot make firm recommendations…” 12
Treatment alternatives • No anticoagulation • Antiplatelet: ASA and/or clopidogrel • Re-initiate warfarin • Factor Xa inhibitors – Rivaroxaban – Edoxaban – Apixaban • Dabigatran 13
PICO P Patients with indication for anticoagulation but have suffered subdural hematoma Anticoagulation or antiplatelet I C Anticoagulation, antiplatelet, or placebo O Mortality, recurrent ICH, recurrent ischemic stroke, disability, bleed requiring hospitalization 14
Search strategy and results • PubMed, Medline • [exp Hematoma, Subdural] AND [Stroke or Atrial Fibrillation or Warfarin] AND [Anticoagulation] • Clinical trials, cohort studies, observational studies • 2 prospective observational, 1 single-arm prospective trial 15
De Vleeschouwer et al. 6 Single-centre prospective observational study Design Patients admitted Jun 1993-Dec 2000 with ICH Patient - 28 had subdural hematoma (SDH), 56 had non- population valvular A-fib (most common OAC indication) N = 108 - Median INR upon admission = 3.7 If OACs were restarted, occurrence of thromboembolic Outcomes event (TE: stroke or VTE), recurrent ICH - Median time to restarting OACs = 11 days Results - 0/25 pts who restarted had TE (n = 25 for - 8/81 pts who did not restart had TE. restarting - 3 dead, 5 severely disabled. OAC) - No SDH in non-restarters - Of those with SDH who experienced recurrent SDH while on OAC, 3 out of 4 made a good recovery 16
De Vleeschouwer et al. 6 Conclusions More prospective research needed for late management Criticisms - Enoxaparin started in all for inpatient VTE prophylaxis - Confounding by indication: majority had prosthetic valves - Heterogeneous population 17
Claassen et al. 7 Design Single-centre prospective observational study Patient -Patients admitted Nov 2001-Dec 2005 for warfarin- population associated ICH (WAICH) N = 48 - Most ICHs were lobar in nature - Avg age 70.8 in restarted arm, most had comorbid A-fib and HTN. - Counted as “restarted” if <60 days from ICH. Outcomes Mean follow-up = 43 months. Recurrent non-traumatic WAICH, traumatic ICH, extracrainal hemorrhage, thromboembolic stroke, PE, distal arterial embolus. Results OAC no OAC (n = 23 for - Thromboembolic stroke: 0/23 vs. 3/25 restarting - VTE: 0/23 vs. 2/25 OAC) - Traumatic ICH: 2/23 vs. 0/25 - GI hemorrhage: 2/23 vs. 2/25 18
Claassen et al. 7 Conclusions WAICH uncommon with resumption. Defer to clinical judgement. Lobar ICH: not resuming warfarin may result in VTE, but risk of traumatic ICH not zero. Criticisms - No documentation whether pts were on antiplatelets - Did not mention if VTE prophylaxis was utilized - Did not reach statistical significance - Only patients where warfarin was suspected cause for ICH 19
Yeon et al. 8 Design Prospective single-arm, single-centre trial Patient - Patients admitted Feb 2008-Apr 2010 for burr hole population drainage N = 20 - Had warfarin +/- antiplatelets, chronic or acute SDH, and an INR of >1.5 upon presentation . - Warfarin restarted 3 days after - Mean CHADS2 = 2.1; mean INR = 2.64 Outcomes Regular INR monitoring and brain CT scans Results - Recurrent SDH documented by CT head within a month of surgery = 3/20 - Any other ICH = 0/20 - Extracrainal hemorrhage within 6 mos = 0/20 - Ischemic stroke/TIA/VTE within 6 mos = 0/20 20
Yeon et al. 8 Conclusions Restarting warfarin therapy can be done 3 days post-op for SDH. Begs a comparative trial for warfarin resumption post-burr hole drainage Criticisms - Target INR in study was 1.7-2.5 - CHADS2 only validated in A-fib patients = 25% pts in trial - No comparator group and only included surgery pts 21
Summary of evidence Study Days to Strokes Recurrent restart OAC and VTE ICH from ICH ↓ * ↑ *, De Vleeschouwer Median 11 but ↓ et al (2005) disability ↓ * ↑ * Claassen et al <60 (2008) Yeon et al (2012) 3 0/20 3/20 22
Recommendation/rationale • Recommend D/C ASA PO and supps • Recommend start warfarin 4 mg PO daily, INR target 2-2.5, INR to be taken day 3 after initiation • Recommend start dalteparin 5000 units SC BID for at least 5 days, D/C when INR is 2-2.5 • Warfarin toxicity reversible • Only case reports exist for NOACs – ARISTOTLE 9 cannot be applied – subgroup analysis NNT 434 for ↓ ICH, 1.5% of pts had CrCl <30 mL/min • CrCl >20 mL/min, no need for heparin 23
Monitoring plan Parameter Change When ↑ to 2 -2.5 INR 3 days Heart rate Keep at 60-110 bpm Ongoing daily Arrhythmias Subjective sensation of palpitations, Ongoing daily room spinning Blood pressure Decrease to <150/90 mm Hg Ongoing daily ICH Presence of FAST symptoms, Twice daily headache or cognitive changes from baseline Cardiogenic Presence of FAST symptoms Twice daily ischemic stroke Bleeding from Presence of bleeding gums, BRBPR, Ongoing daily gums, rectum coffee ground stools/emesis VTE Hemoptysis, SOB, unilateral leg Ongoing daily swelling/tenderness 24
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