BUDGET IMPACT ANALYSIS OF APIXABAN VERSUS OTHER NOACs FOR THE

PREVENTION OF STROKE IN ITALIAN NON-VALVULAR ATRIAL FIBRILLATION

PATIENTS

L.Pradelli1, MD, M.Calandriello2, MBA, R.Di Virgilio3, MD, M.Bellone1, PharmD, M.Tubaro4, MD 1 AdRes Health Economics & Outcomes Research, Turin Italy, ² Bristol-Myers Squibb, Rome Italy, ³ Pfizer, Rome Italy, 4 ICCU, Cardiovascular Department, San Filippo Neri Hospital, Rome Italy

• The different safety and effectiveness profiles of the available NOACs emerging from the adjusted indirect

comparison indicate that the introduction of apixaban could improve health care expenditure control while

maintaining or increasing therapeutic appropriateness in the Italian NVAF population, due to lower costs for

managing thromboembolic and bleeding events.

Conclusions

References

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16. IMS Health of MAT September 2012, market shares of anticoagulants in atrial fibrillation (data on-file)

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Among available NOACs, apixaban is expected to be the least expensive at 1,2, and 3 years (Table II); the

excess pharmaceutical cost, due to improved persistence with the prescribed AC regimen with apixaban, is

completely offset by reduced costs for event management, leading to the overall saving.

In an estimated patient population of 363,994 Italian patients, the introduction of apixaban will temper the cost

associated with expanding market shares of NOACs, allowing for savings of over 5 million € by the third year

(Table III).

The analysis on a non-experimental population of NVAF patients confirms the estimates of the base-case

analysis (Figure II).

Exclusive use of apixaban for three years in the identified population would allow for savings of € 8,8 million, €

14,4 million and € 27,3 million when compared with dabigatran 110 mg, dabigatran 150 mg and rivaroxaban,

respectively.

Results

This study aims to perform a budget impact analysis (BIA) of the use of

three available novel oral anticoagulant agents (NOACs) for preventing

thromboembolic events in Italian patients with non-valvular atrial

fibrillation (NVAF).

The BIA evaluates the financial impact of apixaban introduction by

comparing expected 1,2, and 3 years costs in scenarios with and without

apixaban.

Objective

• This analysis was funded by Bristol-Myers Squibb and Pfizer. LP and MB are employees of AdRes which

received funding from Bristol-Myers Squibb and Pfizer in connection with conducting this analysis and

development of this poster.

Acknowledgements

Ischemic and hemorrhagic strokes are the main complication of non-

valvular AF (NVAF) [1]. Anticoagulation therapy is recommended to

prevent these thromboembolic complications [2].

Novel oral anticoagulant agents (NOACs) have been recently introduced

for prevention of stroke and systemic embolism in adult NVAF patients

who have one or more risk factors.

Apixaban and rivaroxaban are direct and highly selective active site

inhibitors of factor Xa, that reduce the conversion of prothrombin in

thrombin, whilst dabigatran is a potent, competitive, reversible direct

thrombin inhibitor [3].

Background

Estimated Italian population of patients is run through a previously

published decision tree/Markov model [4], simulating their treatment with

the available therapeutic options: dabigatran at two dose levels (110

mg/bid for the over 80 years old, 150 mg/bid for younger NVAF patients),

rivaroxaban, and apixaban.

The effectiveness and safety profile of apixaban reflects event rates

recorded in the ARISTOTLE trial [5].

For the competing NOACs (dabigatran 110 mg, dabigatran 150 mg and

rivaroxaban) effectiveness parameters derive from adjusted indirect

comparison, using warfarin as common comparator, due to lack of head-

to-head trials [4].

Main clinical outcomes monitored are ischemic (IS) and hemorrhagic

stroke (HS), systemic thromboembolism (SE), myocardial infarction (MI),

bleeds (Bs) (both major and clinically relevant minor), cardiovascular

hospitalizations (CV-H), and death. Expected survival is projected

beyond trial duration using national mortality data [6] adjusted for

individual clinical risks [4].

Direct health care unit costs (€), updated at 2013 values [6], include drug

acquisition [7], routine visits [8], IS and HS [9], MI [10], Bs management

and CV-H [11], and other health care costs associated with anticoagulant

(AC) management [11].

Italian NVAF patient population estimation (Table I) is based on official

apixaban reimbursement criteria issued by Italian Medicines Agency

(AIFA) [12,13,14], applying the characteristics of the trial population to

national epidemiologic data [15,16].

The expected penetration of NOACs on the market in the next years has

been estimated based on the market evolution in the first period from the

approval of NVAF as indication for the NOACs [16]; in the scenario with

apixaban, an increasing percentage of the NOAC – treated population is

prescribed apixaban, with shares subtracted proportionally to the

comparators.

Further simulation is performed on non-experimental population of NVAF

patients: clinical and demographic features, gathered by Olesen study

[17], are applied to Italian epidemiologic data [15,16].

A comparison analysis of cost accruing after three years for the

treatment of the whole identified patient population with one of the

available NOACs is performed, in order to highlight the total potential

budget impact of systematically choosing just one of the NOACs for this

indication.

Methods

% N

Residents Italy [6] 61,175,388

AF Prevalence [15] 1.70% 1,039,982

% NVAF [18] 70% 727,987

Eligible to NOACsa 50% 363,994

Year 1 Year 2 Year 3

Apixaban € 1,425 € 2,961 € 4,436

Dabigatran 110 mg € 1,449 € 2,992 € 4,461

Dabigatran 150 mg € 1,459 € 3,007 € 4,476

Rivaroxaban € 1,459 € 3,020 € 4,511

Scenarios 1st year 2nd year 3rd year

Target patients Common 363,994 363,994 363,994

Warfarin 292,790 230,513 213,435

Dabigatran (110 mg) w/o apixaban 20,107 36,551 40,654

w/ apixaban 9,414 14,093 11,407

Dabigatran (150 mg) w/o apixaban 25,383 46,144 51,323

w/ apixaban 11,884 17,792 14,401

Rivaroxaban w/o apixaban 25,714 50,786 58,582

w/ apixaban 12,039 19,582 16,437

Apixaban w/o apixaban 0 0 0

w/ apixaban 37,867 82,014 108,314

Budget Impact -€ 1,180,549 -€ 3,841,429 -€ 5,368,918 Figure II. Total costs of current scenario (w/o apixaban) and

alternative scenario (w/ apixaban) at 1st,2nd, and 3rd year. Yellow and

orange diamonds indicate the total costs on non-experimental (non-

Ex) patient population in w/o and w apixaban scenarios, respectively.

€ 420 € 927 € 1.417

1 year 2 year 3 year

€ M

ilio

n

Alternative scenario (w/ apixaban)

Alternative scenario (w/ apixaban)_non-Ex

€ 421 € 931 € 1.423

Current scenario (w/o apixaban)

Current scenario (w/o apixaban)_non-Ex

Table I. Patients flow for budget impact

analysis.

a. AIFA criteria for reimbursement:

• NVAF with both CHAD₂S ₂ -VASC ≥ 1 and

HAS-BLED >3 [12,13];

• time in therapeutic range (TTR) < 70% [14]

or objective difficulties in measuring INR

Table III. Budget impact: calculated as the difference among the total costs

expected without and with the introduction of apixaban.

Table II. Cumulative cost per patient for each NOAC. Cost details are shown

in panel A, B and C at 1st, 2nd and 3rd year, respectively.

€ 0

€ 300

€ 600

€ 900

€ 1.200

€ 1.500

Totalcost

AC IS HS SE Bs MICV-H

Othercosts

ApixabanDabigatran 110 mgDabigatran 150 mgRivaroxaban

€ 0

€ 600

€ 1.200

€ 1.800

€ 2.400

€ 3.000

Total cost AC IS HS SE Bs MICV-H

Othercosts

Apixaban

Dabigatran 110 mg

Dabigatran 150 mg

Rivaroxaban

€ 0

€ 800

€ 1.600

€ 2.400

€ 3.200

€ 4.000

€ 4.800

Totalcost

AC IS HS SE Bs MICV-H

Othercosts

ApixabanDabigatran 110 mgDabigatran 150 mgRivaroxaban

A.

C. B.

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