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

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

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

Cost-Effectiveness of Prasugrel

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

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

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)

Cost-Effectiveness: Base Case D Cost = -$221 D Life Exp. = 0.102 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)

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)

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)

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)

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

Cost-Effectiveness of Ticagrelor

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

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

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?

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: 220-228.

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: 220-228.

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

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

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

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?

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