ALI R. RAHIMI, BOBBY WRIGHTS, MD, HOSSEIN AKHONDI, MD & CHRISTIAN M. RICHARD, MSC

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

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

9. Nature of the variables collected 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

10. Results

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