The Cost of Clopidogrel Use in Atrial Fibrillation

1. The Cost of Clopidogrel Use in Atrial Fibrillation A Health Economic Analysis of ACTIVE-A Andre Lamy Wesley Tong Peggy Gao Susan Chrolavicius Salim Yusuf Stuart J Connolly

2. Role of the Sponsor • The ACTIVE A trial and this economic analysis were funded by grants from sanofi-aventis and Bristol-Myers Squibb. • The authors had free access to the complete study data and performed all of the analyses independently.

3. The ACTIVE A trial • The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events – Aspirin trial • Clopidogrel with aspirin (C+A) vs aspirin alone • For patients with atrial fibrillation unsuitable for vitamin K antagonist • 7554 patients in 33 countries • AF patients at high risk of stroke • N Eng J Med 2009; 360:2066-78

4. Stroke Graph courtesy of the ACTIVE group

5. Stroke Types and Severity Table courtesy of the ACTIVE group

6. Summary of Clinical Findings • The risk of stroke was reduced by 28% • However the risk of major bleeding increased by 57% • Most common site was the GI tract. • In 1000 patients treated for 3 years, clopidogrel with aspirin will: • Prevent 28 strokes (17 fatal/disabling) • Prevent 6 Myocardial Infarctions • Result in 20 major bleeds (3 fatal)

7. ACTIVE-A Economic Analysis • Clopidogrel + aspirin shown to reduce stroke risk but increase risk of bleeding • Objective: To determine the economic impact of adding clopidogrel to aspirin in the ACTIVE-A population

8. Design • In-trial analysis • Study time horizon used (average follow-up: 3.6 years) • Only direct medical costs • Based on utilization data from CRFs • Canadian healthcare perspective • All costs in 2008 CAD • Discounted at 3% per year • Hypothesis: Clopidogrel + aspirin is cost neutral compared to aspirin alone.

9. Cost Components Average Cost Per Patient Study drug Events Procedures Non-study drugs List Price ODB Formulary Drugs Treatments HHS OCCP Length of Stay Investigations

10. Cost of Stroke • Stroke costs include: • Hospital • Ambulatory care • Physician fees • Tests and procedures • All medications • Assistive devices • Allied health professionals • Home modifications • Caregiver expenses • Goeree R, Blackhouse G, Petrovic R, Salama S. J Med Econ 2005;8:147-67

11. Unit Costs

12. Statistical Analysis • Bootstrap method (5000 samples) for SE and 95% CI. • Bias corrected and accelerated method for confidence intervals Sensitivity Analyses • Clopidogrel cost ($2.52/day 2008 CAD) • 50% of base • 200% of base

13. Results

14. Results $14,132 $13,756

15. $16,289 $13,756 $14,132 $13,054

16. Limitations • Only direct health care costs (mostly hospitalizations) • Indirect costs for C+A vs A alone presumably lower due to fewer strokes • Wide Confidence Intervals (CI) • Due to large standard error in event cost • Bootstrapping and jackknife showed similar results • Absolute difference in cost is within predefined margins for cost neutrality (+/- 5%)

17. Applicable to the United States? • Resource Utilization • No likely significant difference as treatments of AF patients are similar. • Unit costs • Canadian costs are comparable to Medicare costs. • Cost of clopidogrel will be the determinant factor between cost-saving, cost-neutral or cost-effective

18. Conclusion • Cost of clopidogrel + aspirin not significantly different from aspirin alone • Supports the use of clopidogrel + aspirin in patients unsuitable for Vitamin K antagonist therapy in the ACTIVE-A trial

20. Results with CIs

21. Sensitvity Analysis – Drug Cost

22. Bleeding Table courtesy of the ACTIVE group

23. Benefits and Risks: Compared to Warfarin *Hart RC et al. Meta-analysis: Antithrombotic therapy to prevent stroke in patients who have non-valvular AF . Ann Intern Med 2007: 146: 857-67 Table courtesy of the ACTIVE group