1. Cost Analysis: Is it Still Cost Effective to Use Prasugrel or Ticagrelor vs. Generic Clopidogrel?
Adnan K. Chhatriwalla, MD
Saint-Luke’s Mid America Heart Institute
Assistant Professor of Medicine
University of Missouri-Kansas City School of Medicine

2. Adnan K. Chhatriwalla, MD
I/we have no real or apparent conflicts of interest to report.

3. Background
Recently, prasugrel and ticagrelor have been approved for use in patients with ACS
Although these agents offer clear benefits over standard anti-platelet therapy (i.e., ASA + clopidogrel), they also are associated with specific risks (e.g., bleeding) and higher costs
Economic factors are an important consideration in identifying the optimal patient population and treatment duration for these agents

4. Cost-Effectiveness of Prasugrel

5. Mahoney EM, et al. Circulation 2010;121:71-9

6. Economic Study Design Study population: All patients from 8 countries
United States – Italy
Canada – Spain
Australia – UK
Germany – France
Analytic Perspective: U.S. healthcare system
Time Horizon: Lifetime

7. Economic Study Methods
Medical resource utilization tracked for all patients from randomization through last f/u visit
Costs were calculated by multiplying resource counts by U.S.- specific unit costs derived from Medicare data
Study drug costs were based on net wholesale price as of 8/09
Clopidogrel = $4.62/day ($141/month)
Prasugrel = $5.45/day ($166/month)
Life expectancy for each surviving pt was calculated using statistical models based on long-term f/u of a comparable group of ACS patients (from Saskatchewan Canada)

8. Cost-Effectiveness: Base Case
D Cost = -$221 D Life Exp. = yrs
ICER = Dominant
% Dominant: 79.7%
D Cost (Prasugrel – Clopidogrel)
Based on these results, prasugrel is economically dominant, meaning that prasugrel improves outcomes while reducing overall costs. Furthermore, the probability that the cost-effectiveness ratio for prasugrel is < $50,000/LYG is 99.8%
% <$50,000/LYG: 99.8%
D Life Years (Prasugrel – Clopidogrel)

9. Subgroup Analyses ∆ Cost D Life Expect. ICER % Dom-inant % Dom-inated
% < $50K/LYG
Diabetes
-$695
0.183
Dominant
86.5%
0.6%
97.9%
No Diabetes
-$94
0.078
63.2%
2.9%
95.0%
STEMI
-$547
0.145
78.5%
1.6%
95.5%
NSTEMI/UA
-$139
0.091
70.3%
0.9%
98.3%
DES
$26
0.080
$326/LYG
44.0%
3.0%
95.1%
No DES
-$875
0.180
92.3%
0.2%
99.2%
“On-Label” *
-$234
0.128
78.4%
0.1%
99.9%
Furthermore, if we analyze specific subgroups, we find that prasugrel treatment is cost-effective in the presence or absence of diabetes, in STEMI as well as other ACS, with the use of DES or no DES. In most of these subgroups, prasugrel remains economically dominant.
* Age <75, weight >=60kg, no h/o stroke or TIA (post-hoc)

10. Impact of Generic Clopidogrel
Treatment Over Full Trial Duration
Cost of Generic Clopidogrel = $1/day
Cost = +$996 D Life-years= 0.102
ICER = $9,727/LYG
% Dominant: 0%
D Cost (Prasugrel – Clopidogrel)
When comparing prasugrel therapy to generic clopidogrel at a cost of $1 per day, prasugrel is no longer dominant, but remains cost-effective with an ICER of $9,727/LYG and the probability that the cost-effectiveness ratio for prasugrel is < $50,000/LYG is 98.2%.
% <$50,000/LYG: 98.2%
D Life Years (Prasugrel – Clopidogrel)

11. Cost-Effectiveness of Prasugrel
Generic Clopidogrel- Subgroup Analyses
∆ Cost
D Life Expect.
ICER ($/LYG)
Diabetes
$825
0.183
$4508
No Diabetes
$1426
0.078
$18,282
STEMI
$973
0.145
$6710
NSTEMI/UA
$1381
0.091
$15,175
DES
$1546
0.080
$19,325
No DES
$645
0.180
$3583
“On-Label” *
$1286
0.128
$10,046
Prasugrel remains cost effective when compared to generic clopidogrel for all subgroups, but note that the cost-effectiveness ratios are considerably lower for higher risk patients – such as those with diabetes or STEMI.
* Age <75, weight >=60kg, no h/o stroke or TIA (post-hoc)

12. Impact of Generic Clopidogrel by Time Period
Treat Days 1-30
Summary Statistics
D Cost = -$92 D Revasc = 0.056
ICER = Dominant
% Dominant: 70.1%
% <$50K/LYG: 96.9%
Extend treatment from Day 31 to End of Trial
Summary Statistics
D Cost = +$1088
D Revasc = 0.053
ICER = $20,714/LYG
% Dominant: 0.0%
% <$50K/LYG: 84.5%
Finally, if we look at the impact of generic clopidogrel by time period, we find that prasugrel remains dominant in the first 30 days after treatment and that it remains cost-effective, but no longer dominant after 30 days, with a cost-effectiveness ratio of $20,714/LYG

13. Cost-Effectiveness of Ticagrelor

14. Nikolic, et al. Eur Heart J 2013; 34: 220-228.

15. Economic Study Design
Study population: ACS patients enrolled in PLATO n=10,686
Analytic Perspective: Swedish healthcare system
Time Horizon: Lifetime

16. Economic Study Methods
Medical resource utilization tracked for all patients obtained from PLATO data set
Costs for hospitalizations and physician services calculated by multiplying resource counts by unit costs based on a Swedish setting
Study drug costs:
Clopidogrel = €0.06/day (reimbursed cost in Sweden)
Ticagrelor = € 2.21/day (lowest available price in 7/2011)
Note: 0.06 euros = 8 cents?

17. Cost-Effectiveness of Ticagrelor
Swedish Perspective
Primary Results
D Cost = € 362
D QALYs = 0.13
ICER = € 2753/QALY
Based on these results, ticagrelor is cost effective, with a cost effectiveness ratio of €2753/QALY.
$3672/QALY
Nikolic, et al. Eur Heart J 2013; 34:

18. Ticagrelor: Subgroup Analyses
∆ Cost
D Life Yrs
ICER (€/LYG)
All ACS
€362
0.15
€2372
Unstable Angina
€395
0.13
€3039
NSTEMI
€363
0.16
€2329
STEMI
€355
€2421
Invasive Strategy
€331
€2509
Diabetes
€437
0.22
€2023
Furthermore, ticagrelor the cost-effectiveness of ticagrelor is quite similar in subgroups of patients with …
Nikolic, et al. Eur Heart J 2013; 34:

19. Cost-Effectiveness of Ticagrelor in the U.S.
A “Back of the Envelope” Calculation by David Cohen
I thank my colleage Dr. David Cohen for his “back of the envelope” calculations of the cost-effectiveness of ticagrelor compared to generic clopidogrel in the United States, again assuming a cost of $1/day for generic clopidogrel. Again, ticagrelor appears cost-effective, with a cost-effectiveness ratio of about $14,000/LYG

20. Summary - Prasugrel
For patients with ACS undergoing PCI, treatment with prasugrel as compared with branded clopidogrel is cost saving
When compared with generic clopidogrel, prasugrel is no longer cost-saving but still cost effective
Cost effectiveness most favorable in higher-risk populations (i.e., STEMI, diabetes)
Appears to be reasonably cost-effective even after the first month

21. Summary - Ticagrelor
Ticagrelor also appears to be cost-effective compared with either branded or generic clopidogrel
Findings mainly related to significant mortality benefit after 1 year in PLATO
Cost-effectiveness favorable across virtually all patient subsets, based on Swedish cost data

22. Limitations and Questions
Two important assumptions
Prasugrel - that non-fatal MI in TRITON TIMI-38 has long-term prognostic significance similar to that seen in other observational studies
Ticagrelor - that the mortality reduction is “real” and applies to the North American population as well.
How does clopidogrel responsiveness impact cost-effectiveness?

23. Thank You