Presentación "Análisis de coste efectividad con los nuevos antiagregantes. Causas de infra-utilización en España" del Dr. José Luis Ferreiro durante la Mesa Redonda de Antiagregación de la XXV Reunión Anual de la Sección de Hemodinámica y Cardiología Intervencionista (SHCI) de 2014 en Córdoba.

1. Análisis de coste efectividad con los
nuevos antiagregantes.
Causas de infrautilización en España
Mesa redonda: Antiagregación. 12/06/2014
Dr. José Luis Ferreiro
Hospital Universitario de Bellvitge - IDIBELL
Área de Enfermedades del Corazón
Unidad de Cardiología Intervencionista - Laboratorio de Investigación Cardiovascular

2. CONFLICTS OF INTEREST
• Honoraria for lectures:
– Eli Lilly Co; Daiichi Sankyo, Inc.; AstraZeneca; Roche
Diagnostics
• Advisory boards:
– AstraZeneca; Eli Lilly Co; Ferrer, The Medicines
Company
• Research grants:
– Spanish Society of Cardiology; AstraZeneca

3. DISCLOSURES
• I am not an expert in cost-effectiveness…
…but I will do my best
• The intention is to compare certain aspects of
new P2Y12 inhibitors (not among them) vs.
clopidogrel

4. INDEX
• Cost-effectiveness
• Underuse of new antiplatelet agents in Spain?
• Reasons for underutilization

5. COST-EFFECTIVENESS

6. Clopidogrel Prasugrel Ticagrelor
PVP IVA
Clopidogrel 75mg 28 comp:
21,04€ (costof reference)
Efient 10mg 28 comp: 63,38€
Efient 5mg 28 comp: 57,68€
Brilique 90mg 56 comp: 89,61€
Cost of treatment
(year) 280 € 824 € 1.171 €
Incremental cost
(year) + 544 € + 891 €
Incremental cost of treatment with the new ADP antagonists
COST-EFFECTIVENESS

7. ACS
Variable Prasugrel Ticagrelor
NNT (CI 95%) ICE (CI 95%) NNT (CI 95%) ICE (CI 95%)
CV death, non-fatal MI,
non-fatal stroke
43 (33-88) 25.024 €
(17.408-47.872 €)
56 (39-113) 49.896 €
(34.749-100.683 €)
CV death -- n.a. 95 (69-223)
84.645 €
(57.024-206.712 €)
Non-fatal MI 46 (33-73)
25.024 €
(17.952-39.712 €)
93 (60-300)
82.683 €
(53.460-267.300 €)
Non-fatal stroke -- n.a. -- n.a.
Death by any cause --
n.a.
79 (56-158)
70.389 €
(49.896-140.778 €)
Stent thrombosis
81 (65-117) 44.064 €
(33.360-63.648 €)
1.771 (106-590)
157.451 €
(94.446-525.690 €)
Incremental cost-effectiveness compared to clopidogrel
Prasugrel: 15 months / Ticagrelor: 12 months
COST-EFFECTIVENESS
Too simplistic approach…

8. COST-EFFECTIVENESS
AVAC / QALY
USA: 50.000$ = 36.275€
UK: 30.000£ = 35.190€
Prasugrel Ticagrelor
ACS 3.435£ (4.029€) ACS 3.521£ (4.130€)
STEMI 2.167£ (2.542€) STEMI 2.551£ (2.992€)
NSTEACS / UA 4.494£ (5.271€) NSTEACS 5.217£ (6.120€)
UA 5.310£ (6.229€)

9. COST-EFFECTIVENESS
Cost-effectiveness acceptability curve in Spain
ACS-PCI ACS
Davies A et al. Farm Hosp. 2013;37:307-16 Delgado JL et al. XXXII Jornadas de Economía de la Salud. 2012
Prasugrel Ticagrelor
SCA 9.489 € SCA 3.944 €
IAMEST 5.913 € IAMEST 4.035 €
SCASEST / AI 12.414 € SCASEST 3.860 €
AI 4.971 €
Prasugrel and ticagrelor are more cost-effective than clopidogrel
with a threshold of 30.000€/QALY gained
Differences in methodology: unable to compare among drugs

10. UNDERUSE OF NEW
ANTIPLATELET AGENTS IN SPAIN?

13. USE OF NEW P2Y12 ANTAGONISTS
STEMI NSTEACS
SWEDE-HEART Registry
Wallentin L et al. Thromb Haemost. 2014;112
Orange = Clopidogrel and Ticagrelor
Purple = Ticagrelor
Yellow = Clopidogrel and Prasugrel
Pink = Prasugrel
Green = Clopidogrel

14. USE OF NEW P2Y12 ANTAGONISTS
Alexopoulos D et al. Am Heart J. 2014;167:68-76.e2
GRAPE Registry: 8 PCI hospitals from Greece
In-hospital treatment
Use of new APT
(only+switch)
Overall (n=1794) 59.3% (489 + 575)
STEMI (n=941) 63.4% (335 + 262)
NSTEMI + UA (n=853) 54.7% (154 + 313)

15. Source of data: IMS Health.
UNDERUTILIZATION IN SPAIN?
April 2014 PRASUGREL TICAGRELOR CLOPIDOGREL
ESPAÑA 11,3 9,8 71,3
ANDALUCIA 12,4 11,6 69,1
ARAGON 6,6 10,5 73,9
ASTURIAS 4,3 6,8 76,0
BALEARES 8,8 15,4 65,5
CANARIAS 12,5 7,1 76,4
CANTABRIA 14,0 5,1 63,6
CASTILLA LA MANCHA 11,0 14,7 67,6
CASTILLA Y LEÓN 14,3 5,3 72,5
CATALUÑA 8,8 8,3 78,1
CEUTA 9,2 4,0 78,2
C. VALENCIANA 12,5 12,5 66,2
EXTREMADURA 8,2 18,8 64,3
GALICIA 5,4 1,8 83,3
LA RIOJA 11,5 10,6 68,9
MADRID 12,5 12,5 66,8
MELILLA 17,2 11,7 80,8
MURCIA 4,5 9,5 71,3
NAVARRA 8,7 9,7 77,9
PAIS VASCO 8,2 1,7 65,6
Market share / Percentage of sales (not percentage of patients)
Caution with interpretation:
What is the percentage of clopidogrel due to an ACS?
Differences in cost (e.g. if a drug is more expensive, this value
overstimate the real percentage of patients treated)

16. Source of data: IMS Health.
UNDERUTILIZATION IN SPAIN?
April 2014 PRASUGREL TICAGRELOR CLOPIDOGREL
ESPAÑA 3,7 2,2 92,0
ANDALUCIA 4,1 2,7 92,0
ARAGON 2,1 2,3 94,3
ASTURIAS 1,3 1,4 94,5
BALEARES 3,0 3,7 92,2
CANARIAS 3,9 1,6 92,5
CANTABRIA 4,5 1,2 91,0
CASTILLA LA MANCHA 3,7 3,5 90,1
CASTILLA Y LEÓN 4,6 1,2 93,1
CATALUÑA 2,7 1,8 93,9
CEUTA 2,8 0,8 95,0
C. VALENCIANA 4,2 3,0 91,2
EXTREMADURA 2,8 4,6 90,3
GALICIA 1,5 0,4 95,3
LA RIOJA 3,6 2,4 86,5
MADRID 5,9 2,8 88,3
MELILLA 1,4 2,0 96,6
MURCIA 2,8 2,2 93,7
NAVARRA 2,3 0,3 87,5
PAIS VASCO 5,0 1,0 89,0
DOTs (days of treatment), accounting sales by price and pills/day
Caution with interpretation:
What is the percentage of clopidogrel due to an ACS?

17. UNDERUTILIZATION IN SPAIN?
Let’s play… (do not consider as real data)
% of clopidogrel due to
ACS
Clopidogrel
New agents
(Prasugrel + Ticagrelor)
25% due to ACS 79.7% 20.3% (12.7 + 7.7)
50% due to ACS 88.7% 11.3% (7.0 + 4.3)
75% due to ACS 92.2% 7.8% (4.8 + 3.0)
Assuming use only of clopi / pras / tica in ACS…
It might even vary among regions…

19. REASONS FOR
UNDERUTILISATION

20. REASONS FOR UNDERUTILIZATION
• Increased short-term costs
– Cost-effectiveness often not considered
• Therapeutic / Clinical inertia
– Failure of health care providers to initiate or intensify therapy
when indicated
– Encompasses the underuse of therapy that is efficacious and
effective in preventing serious endpoint clinical outcomes
– Particularly important in common chronic diseases in which
certain therapies have adequate evidence of effectiveness
Allen JD et al. J Manag Care Pharm. 2009;167:690-5

21. Allen JD et al. J Manag Care Pharm. 2009;167:690-5
Factors contributing to apparent clinical inertia (hypertension)
THERAPEUTIC INERTIA
Non-Adherence

22. BALANCING ISCHEMIA / BLEEDING
Inhibition of platelet aggregation
High risk of
ischemic events
High risk of
bleeding events“Sweet spot”
Ischemic risk Bleeding riskIschemic risk Bleeding risk
Ferreiro JL et al. Thromb Haemost 2010;103:1128-35.
Several agents: Individualize therapy
‘‘The lower the bleeding risk, the higher the ischemic risk’’

23. CONCLUSIONS
• Prasugrel and Ticagrelor are cost-effective when compared to clopidogrel
• New P2Y12 antagonists in Spain probably underused
– Differences among regions
– Concern: interruption/change of treatment during follow-up
• Several reasons for underutilization:
– Short-term costs
– Therapeutic inertia: Proactive measures are needed
• Challenge: Not to reach a percentage, but to individualize therapy
(balance ischemia/bleeding) and choose the best drug for each patient

24. GRACIAS POR SU ATENCIÓN