1. ALI R. RAHIMI, BOBBY WRIGHTS, MD, HOSSEIN AKHONDI, MD & CHRISTIAN M. RICHARD, MSC Clinical Correlation Between Effective Anticoagulants & Risk of Stroke: Are We Using Evidence-Based Strategies Trina La PharmD. Candidate Oct 20 th, 2011 Southern Medical Journal 2004;97: 924-931

2. Introduction Atrial fibrillation (AF) can predispose patients to blood clots that can cause stroke If untreated, one in three people with nonvalvular AF will suffer a stroke The importance & efficacy of anticoagulation therapy in preventing a stroke is a common knowledge & has become the standard of care

3. Introduction Warfarin was reported to be substantially more efficacious than aspirin Anticoagulant prophylaxis is effective as INR of 2 to 3, and is associated with a lower risk of bleeding However, despite extensive evidence & recommendations for its use, anticoagulant prophylaxis is underused in the management of AF

4. Study’s Objective Primary endpoint: To define correlation between effective anticoagulant prophylaxis and risk of thromboembolic stroke Secondary endpoint: To observe & investigate the role of other factors, such as practice patterns in different settings

5. Study Design Patients with a diagnosis of AF requiring anticoagulation therapy & who were admitted between years 1997 & 2000 to community-based teaching hospital in Southeast Georgia were identified through a retrospective chart review The sample consisted of 297 patients  91 patients who suffered a stroke at any point during the study period  206 patients who did not suffer a stroke by the end of year 2000

6. Study design Patients demographics, clinical diagnoses, findings & treating physicians were extracted from admission records History of AF, duration of the disease, treatment modalities, indicators for anticoagulation therapy, & risk factors for comorbid diseases were obtained from hospital charts

7. Study design Two study groups  Warfarin: 124 patients  No Warfarin: 166 patients  No record of anticoagulation therapy: 7 patients INR  Between 2.0 & 3.0 as therapeutic Prescribing physician specialties  Neurologists  Cardiologists  General internists  Others

8. Inclusion Exclusion A diagnosis of AF requiring anticoagulation therapy Hypercoagulable state Hemorrhagic stroke Carotid stenosis Peripheral vascular disease Dilated cardiomyopathy Inclusion & Exclusion

9. Variables collected Data Analysis Age INR Gender Race Co-morbidities Managing Physician Specialty Normal probability plots & the Shapiro-Wilks test to assess the normality assumption Chi-square test of independence to compare patients prescribed/not prescribed warfarin for each indicator variables The risk of stroke associated with anticoagulation tx was assessed using 2x2 contingency table & stratified Mantel-Haenszel analysis Nature of the variables collected

10. Results VariablesWarfarin (n=124) Non-Warfarin (n=166) Statistical test P value Age72.95 ± 10.6074.23 ± 11.920.232 Gender Male Female 46.8% 53.2% 44.8% 55.2% 0.754 INR2.51 ± 2.031.19 ± 0.45<0.001 Comorbidities CVA CHF CAD HTN Diabetes 24.2% 29.8% 22.6% 54.8% 25.0% 13.3% 27.1% 18.1% 58.4% 25.9% 0.017 0.610 0.342 0.541 0.861 Managing physician Specialty Cardiology Neurology Internal Med Other 30.6% 13.7% 33.1% 22.6% 16.9% 10.8% 39.2% 33.1% 0.02 Stroke19.4%37.3%<0.001

11. Results Higher warfarin dosages  Larger values in INR (r=+0.395)  Fewer strokes (r=-0.372)  Prescribed by cardiologists (0.289) Greater occurrences of strokes are present in those patients under the care of neurologist (r=+0.394) Average dosage of warfarin prescribed  Cardiologists: 2.94 mg  Neurologists: 1.76 mg

12. Odds of Warfarin Prescription Patients who were more likely to be prescribed warfarin when  History of AF & stroke (P=0.013)  Care management by a cardiologists (P=0.035) Elderly patients were more likely to have additional comorbidities that influenced the prescription of warfarin Neurologists (P=0.308) & internists(P=0.77) have similar patterns of prescribing warfarin when compared with cardiologists

13. Odds of Stroke Patients who are not prescribed warfarin have significantly higher risk of suffering a stroke Patients with diagnosis of CHF in addition to AF were 6.8 times less likely to suffer a stroke when compared with AF patients without CHF NNT: 50

14. Author’s comment Treatment of AF & anticoagulant prophylaxis are complex & time consuming clinical undertakings that requires long-term commitments This study’s result with regard to the risk of stroke in patients with AF are consistent & in line with previously published studies The elderly patients and the presence of co-morbid diseases play a significant role in the decision making process

15. Limitations & Conclusion Limitations  Many patients’ records revealed the presence of internist in addition to other specialists  There were some overlaps between the primary providers in ordering warfarin dosages Conclusions  Despite extensive evidence supporting anticoagulation therapy, both physicians & patients are less inclined to more aggressive stroke prevention measures  Cost, fear of bleeding complications, drug interactions, & time are the factors influencing decision making  educational opportunities & an aggressive public awareness might be needed

16. Comments I think this is a very important study because it showed the correlation between effective anticoagulant on stroke prevention, and it raised the awareness of not fully use evidence-based strategies per physicians However, the study did not document some essential information  History of compliance with warfarin  When patients started taking warfarin  How the physician adjust warfarin dosing  Record of all medications, including AF medications due to potential drug interaction  History of adverse drug events and complications

17. Level of evidence