A Stroke of Luck in Atrial Fibrillation

1. A Stroke of Luck in Atrial Fibrillation Steven Du LMPS Resident December 19th, 2013

2. Objective • To describe the epidemiology of cardioembolic stroke in AF • To discuss choice and timing of antithrombotic therapy acutely after stroke in patients with atrial fibrillation

3. Our Patient – HP

4. Review of Systems Nov 25th

5. Investigations

7. PMH/MPTA

8. Current Medications

9. Background • Ischemic stroke: a polyetiologic disease • Cardioembolic strokes account for 25% of ischemic strokes • Associated with highest stroke severity • Atrial fibrillation, recent MI, and mitral valve disease are risk factors for cardioembolic stroke • Early recurrent stroke in AF: 5% in 2 weeks Stroke. 2001; 32: 2559-2566

10. Haemorrhagic transformation • Frequency of any HT in untreated patients was 8.5% • Clinically significant HT accompanied by neurologic deterioration was 1.5% (majority occurred within 4 days of infarct) • Risk factors: large infarcts, mass effect, hypo-density observed early after the stroke, and age older than 70 years, drug therapy J Stroke Cerebrovasc Dis. 2004 Nov-Dec;13(6):235-46 Stroke. 1997 Nov;28(11):2109-18..

11. Drug Therapy Problems • Patient is at risk of recurrent stroke and HT and would benefit from reassessment of his antithrombotic therapy • Patient is experiencing sedation in the daytime and would benefit from reassessment. • Patient is experiencing back pain and would benefit from reassessment.

12. Goals of therapy • Reduce mortality • Reduce risk of recurrent stroke • Reduce long term disability • Minimize ADR

13. Clinical Question

14. Literature Search • Searched: Medline, Embase • Terms: Acute stroke, cardioembolic, atrial fibrillation, anticoagulation, aspirin, warfarin. • Limits: Humans, English, RCT, Meta-analysis, Systematic review • Results: 3 RCT, 2 meta analysis, 1 systematic review

15. Paciaroni et al. Efficacy and Safety of Anticoagulant Treatment in Acute Cardioembolic Stroke: A Meta-Analysis of Randomized Controlled Trials Stroke. 2007 Jan 4;38(2):423–30.

16. Paciaroni et al.

17. Paciaroni et al.

18. Results

19. Conclusions • No reduction in death and disability • Events driven by IST (full dose and low dose heparin arm) • Little heterogeneity in results • Subgroup analysis non significant

20. Our Patient - HP • At risk for HT due to size of infarct • Asymptomatic petechial hemorrhage • Early anticoagulation <48 hours not beneficial vs. either placebo or early aspirin • Applicability to warfarin?

21. Chen et al. Indications for Early Aspirin Use in Acute Ischemic Stroke : A Combined Analysis of 40,000 Patients From CAST and IST Stroke. 2002 Nov 1;33(11):2722–7.

22. Chen et al.

23. Results Death or dependency: 1.2%ARR p = 0.01 Ischemic stroke: 0.7% ARR = <0.000001

24. Subgroup Analysis Recurrent Stroke Recurrent Stroke or death

25. External review of subgroup analysis Stroke. 2002;33:2722-2727.

26. Limitations • IST open label, no placebo • Assessment unblinded • Benefit driven by IST, smaller non significant benefit found in CAST which was double blinded

27. Our Patient - HP • Early ASA has a small but statistically significant reduction in death and disability • Evidence based to start ASA at 24-48hrs post event if early anticoagulation is not started. • Despite caveats mentioned previously, care should be taken when interpreting subgroup analysis

28. Guidelines • “Urgent anticoagulation, with the goal of preventing early recurrent stroke, halting neurological worsening, or improving outcomes after acute ischemic stroke, is not recommended for treatment of patients with acute ischemic stroke” (Class III; Level of Evidence A) • “Oral administration of aspirin (initial dose is 325 mg) within 24 to 48 hours after stroke onset is recommended for treatment of most patients” (Class I; Level of Evidence A) AHA/ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke 2013

29. Guidelines • “The optimal timing of oral anticoagulation following acute stroke for patients in atrial fibrillation is unclear; it is common practice to wait two to fourteen days and repeat brain imaging (CT or MRI) to rule out asymptomatic intracranial hemorrhage” Canadian Stroke Strategy Best Practice Recommendations Update 2010

30. Bottom Line • Urgent anticoagulation? No • ASA within 24-48 hours? Yes • When to start OAC? Clinical judgment • Aspirin bridging? Unclear

31. Our Patient • Around 48 hours out from onset of symptoms when assessed • No significant deficits remaining • Repeat CT was not done

32. Recommendation • ASA 325mg po x 1 dose, then 80mg daily • Start warfarin in 7-14 days If repeat CT shows no hemorrhage or progression, and clinically stable • D/C ASA and dalteparin when warfarin therapeutic

33. Monitoring

34. Course in hospital • Neurologist: Start warfarin (2 days post stroke). No ASA. • Clinically stable. No slurred speech, confusion, minimal motor impairment, near baseline ambulation by discharge. • Patient was counselled on warfarin and discharged on Day 6 of admission after therapeutic INR reached.

35. Questions?