Farmeco 2014;15(Suppl 1)5-14.html

Farmeconomia. Health economics and therapeutic pathways 2014; 15(Suppl 1): 5-14

http://dx.doi.org/10.7175/fe.v15i1S.973

Original Research

Budget impact analysis of apixaban versus other NOACs for the prevention of stroke in Italian atrial fibrillation patients

Lorenzo Pradelli 1, Mario Calandriello 2, Roberto Di Virgilio 3, Marco Bellone 1, Marco Tubaro 4

1 AdRes, Health Economics & Outcome Research, Turin, Italy

2 Bristol-Myers Squibb Italy, Rome, Italy

3 Pfizer Italy, Rome, Italy

4 ICCU, Cardiovascular Department, San Filippo Neri Hospital, Rome, Italy

Abstract

OBJECTIVE: This study aims to perform a budget impact analysis of the use of three available novel oral anticoagulant agents (NOACs) for preventing thromboembolic events in Italian patients with non-valvular atrial fibrillation (NVAF).

METHODS: Estimated Italian population of patients was run through a previously published lifetime decision tree/Markov model 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 (20 mg/uid), and apixaban (5 mg/bid). Effectiveness and safety estimates derive from an adjusted indirect treatment comparison using warfarin as link. The main clinical events considered in the model are ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor) and cardiovascular hospitalizations, besides treatment discontinuations. Epidemiological data and unit costs, actualized to 2013, are collected from Italian published sources. The budget impact analysis evaluates the financial impact of apixaban introduction by comparing expected 1,2, and 3 years costs in hypothetical scenarios: with and without apixaban. Italian NVAF patient population estimation is based on official apixaban reimbursement criteria, applying the characteristics of the trial population to national epidemiologic data. Numbers of patients for each regimen are estimated by projecting share evolution. Sensitivity analysis is performed on an alternative non-experimental population of NVAF patients.

RESULTS: Among available NOACs, apixaban was expected to be the least expensive in an estimated patient population of 364,000 Italian patients, allowing for savings of € 1,180,549, € 3,841,429 and € 5,368,918 at 1,2, and 3 years, respectively. Results of the simulation run on an alternative non-experimental population of NVAF patients yields comparable estimates.

CONCLUSIONS: The different safety and effectiveness profiles of the three available NOACs emerging from the adjusted indirect comparison indicate that apixaban could improve health care expenditure control while maintaining or increasing therapeutic appropriateness in the Italian NVAF population.

Keywords

Apixaban; Novel oral anticoagulant agents; Atrial fibrillation

Corresponding author

Lorenzo Pradelli

l.pradelli@adreshe.com

Disclosure

Study funded by Bristol-Myers Squibb and Pfizer

Introduction

Atrial fibrillation (AF) is the most prevalent form of arrhythmia, involving about 1-2% of the population in industrialized countries [1]. Its prevalence increases with age, reaching values above 5% in the over 65 years old, and of 9% in octogenarians [2].

In Italy, a prevalence of 600,000 AF patients was estimated for year 2010, and a further increase is expected due to the increasing age of the population and the improved survival of cardiovascular patients [3]. Stroke is the main complication of AF [4]: over 20% of ischemic strokes are linked to some form of arrhythmia [1], and in these patients, they tend to be more severe than in non-arrhythmic patients [5]. About 40% of stroke survivors presents moderate to severe disability; applying these rates to the prevalent population, it has been calculated that around 384,000 are not autonomous in Italy due to stroke, and this figure is expected to rise up to 440,000 by 2020 [6].

Therapeutic goals in the management of AF patients include symptom control, but also the prevention of thromboembolic complications, stroke in primis. This was traditionally pursued with the administration of vitamin K antagonists (VKA), or with antiplatelet agents, mainly aspirin, in subjects intolerant or contraindicated to VKAs [7]. In the last years, however, the class of novel oral anticoagulant agents (NOACs) has been introduced, which is associated with a more favourable risk/benefit ratio than VKAs. Until recently, dabigatran, a direct thrombin inhibitor, and rivaroxaban, a direct and selective coagulation factor Xa inhibitor, were the only NOACs licensed for thromboembolic prevention in non-valvular AF (NVAF, about 70% of all AF cases). Apixaban, also a direct and selective coagulation factor Xa inhibitor [8], is facing the launch on the market for this indication, with the following reimbursement restrictions: NVAF with both CHA2DS2-VASc ≥ 11 and HAS-BLED > 32, or time in therapeutic range (TTR) < 70% or objective difficulties in measuring INR [9].

Aim of the present analysis is the comparative, short-term economic evaluation of the use of the three available NOACs in the prevention of thromboembolic events in the indicated Italian population of patients with NVAF. A budget impact analysis for the Italian National Health Service, which covers both the pharmaceutical cost and the costs for management of clinical events is performed to evaluate the financial impact following the entry of apixaban among NOACs.

Methods

The analysis is conducted with a simulation study, performed through the adaptation and run of an international previously published model [10,11] and executed with epidemiological, clinical practice and unit costs pertinent to the Italian setting. The model is designed to reproduce the experience of a cohort of NVAF patients of user defined features, alternatively treated with the available therapeutic options: for the present study, dabigatran at two dose levels (110 mg/bid for the over 80 years old, 150 mg/bid for younger NVAF patients), rivaroxaban, and apixaban. During the simulation, events and consumed resources from the Italian National Health System perspective are recorded by the model; main clinical outcomes monitored are ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor), cardiovascular hospitalizations, and death.

Model structure

The model is designed as a decision tree with Markov chains as branches; the experience of a NVAF patient is divided and represented in 17 possible and mutually exclusive health states (Figure 1). Transitions among health states are determined by probability matrices derived from the relevant literature as detailed elsewhere [11].

At the end of each 6 week cycle, patients can stay in the current health state, or experience a clinical event and forward to the corresponding state; some events only imply a resource consumption, whilst others – i.e. stroke, myocardial infarction (MI), and systemic embolism – also modify the chance of incurring in further events. Stroke survivors distribute among subsequent health states basing on the assigned severity distribution of the specific event. Following a major bleeding, patients may continue to receive the initial anticoagulant, or switch to a second line treatment, associated with specific clinical event risks.

img_01_01.jpg

Figure 1. Simplified structure of the Markov model

Population

The simulation is run on two cohorts (Table I): the first (base-case) reproducing clinical and demographic features of the ARISTOTLE trail population [12], the second those of a non-experimental population of NVAF patients studied by Olesen et al. [13]. In this cohort study, Olesen et al. assessed the individual risk factors composing the CHADS2 and CHA2DS2-VASc score calculating the capability of the schemes to predict thromboembolism in a nationwide cohort of Danish real-world patients.

Base-case – ARISTOTLE population [12]

Alternative case – Real-world population [13]

% males

65

53

Mean age (years)

70

77

CHADS2 score (%)

0-1

34

53

2

36

23

> 2

30

24

Table I. Baseline characteristics of the simulated populations: base-case patient populations, from ARISTOTLE trial [12], and alternative-case population, from a nationwide cohort of real-world patients, registered in the Danish patient registry [13]

Clinical outcomes rates

In general, the model assigns baseline clinical risks basing on the demographic and clinical features of the patients; these risks evolve according to the time elapsed from the beginning of the simulation, to the risk-modifying clinical events experienced by the patient, and to the preventive regimen administered.

The effectiveness and safety profile of apixaban reflects event rates recorded in the ARISTOTLE trial [12] integrated with patient-level data made available by Lip et al. [11], which showed that apixaban was associated with a reduction in the risk of stroke or systemic embolism, in bleeding, and in all-cause mortality in AF patients, as compared to warfarin. The choice of the ARISTOTLE trial, a randomised head-to-head clinical trial, is related to the comparator, warfarin, which is common to the pivotal trials in AF of the other NOACs. The baseline risk profile can be adjusted for different distributions in the simulated population vs. the ARISTOTLE population of the CHADS2 and TTR, for stroke and bleeding, respectively.

Dabigatran was compared to warfarin in AF patients in the RELY trial, in which it demonstrated similar efficacy in stroke and thromboembolic prevention and lower bleeding risk, at the 110 mg bid, and superior stroke and embolism prevention, with similar bleeding risk, at the 150 mg bid dose [14].

Rivaroxaban was compared to warfarin in the ROCKET-AF trial, demonstrating non inferiority in the prevention of stroke and thromboembolism in NVAF patients, and similar bleeding risk [15].

Data from the VKA-suitable population of these trials (ARISTOTLE, RELY, and ROCKET-AF) were included in indirect treatment comparisons, using warfarin as common comparator, to obtain relative risks or hazard ratios of each of the NOACs vs. apixaban, for each evaluated outcome [11] (Table I).

For apixaban, the risk of incurring an ischemic stroke (IS) is directly extrapolated from the ARISTOTLE in the base-case analysis, and adjusted for the CHADS2 distribution in Olesen et al. [13] for the alternative scenario; for the competing NOACs, the rate is calculated by applying the relevant HR to the apixaban hazard in both analyses. Increasing age is associated with higher IS risk; in the model, this is accounted for by applying a HR of 1.4 per decade [16]. Severity distribution of IS is classified according to the modified Rankin scale (mRS – mild 0-2; moderate 3-4; severe 5 and fatal 6) specific to the AC treatment and was derived from published literature (Table II).

Apixaban
[10,11]

Dabigatran (110 mg) [11]

Dabigatran (150 mg) [11]

Rivaroxaban [11]

Aspirin (2nd line) [10,11]

IS*

Rate/100 pts-yr

0.98

3.456

HR (95% CI) vs. apixaban

1.20 (0.88-1.64)

0.82 (0.59-1.14)

0.98 (0.72-1.33)

Pts distribution (%)

  • Mild mRS (0-2)

53

35

35

49

365

  • Moderate mRS (3-4)

21

28

22

18

385

  • Severe mRS (5)

8

10

8

6

155

  • Fatal mRS (6)

18

27

35

27

115

ICH*

Rate/100 pts-yr

0.33

0.326

HR (95% CI) vs. apixaban

0.73 (0.43-1.26)

1.02 (0.62-1.68)

1.73 (1.08-2.77)

Other ICH (%)

23

36

59

43

455

Case Fatality Rates (%)

133

132

132

132

135

Proportion of HS (%)

77

64

41

57

555

  • Mild mRS (0-2)

23

35

35

49

75

  • Moderate mRS (3-4)

32

28

22

18

205

  • Severe mRS (5)

10

10

8

6

275

  • Fatal mRS (6)

35

27

35

27

465

Other MB*

Rate/100 pts-yr

1.79

0.896

HR (95% CI) vs. apixaban

1.21 (0.97-1.50)

1.37 (1.10-1.70)

1.44 (1.15-1.79)

Case Fatality Rates

23

22

22

22

25

Proportion of GI Bleeds

38

41

49

45

395

CRNM*

Rate/100 pts-yr

2.08

2.946

HR (95% CI) vs. apixaban

1.16 (0.99-1.35)

1.30 (1.11-1.53)

1.49 (1.26-1.76)

MI*

Rate/100 pts-yr

0.53

1.116

HR (95% CI) vs. apixaban

1.474 (0.96-2.27)

1.46 (0.95-2.24)

0.94 (0.64-1.38)

SE

Rate/100 pts-yr

0.09

0.404

HR (95% CI) vs. apixaban

12

12

12

Other CV Hosp

Rate/100 pts-yr

10.461

13.576

HR (95% CI) vs. apixaban

12

12

12

Other Treat Disc

Rate/100 pts-yr

13.18

-

HR (95% CI) vs. apixaban

1.45 (1.31-1.61)

1.51 (1.36-1.67)

1.18 (1.08-1.29)

Background mortality°

Rate/100 pts-yr

3.08

-

HR (95% CI) vs. apixaban

12

12

12

Table II. Summary of main clinical inputs used in the analysis

CRNM: Clinically Relevant non Major Bleeds; GI: Gastro-Intestinal Bleeds; HS: Hemorrhagic Stroke; ICH: IntraCranial Hemorrhages; IS: Ischemic Stroke; MI: Myocardial Infarction; Other CV Hosp: Other Cardio-Vascular Hospitalization; Other MB: other Major Bleeds; Other TreatDisc: Other Treatment Discontinuation; pts: patients; SE: Systemic Embolism; yr: year

1 Assume same rate as the apixaban’s rate observed among the VKA unsuitable population

2 Assume same risk as apixaban

3 Pooled sample percentages

4 Assume same rate as ASA first line observed in the VKA unsuitable population

5 Assume same distribution as ASA first line

6 Subgroup of patients who had VKA-unsuitability “demonstrated” (i.e., previously failed warfarin)

* Stroke, bleeds and MI risks are adjusted over time to take into account the increased risks with aging: HR for adjunctive decade of 1.4 [16], 1.97 [17], and 1.3 [20], respectively, are applied

° For the duration of the trial follow-up

As with IS, in the base-case analysis the absolute intracranial hemorrhage (ICH) hazard rate for apixaban is directly obtained from ARISTOTLE; specific HRs are applied to these rates to determine the hazard rates for dabigatran and rivaroxaban. The model accounts for age-related increase in ICH risk by applying a 1.97 HR per decade [17]. Hemorrhagic strokes (HS) are determined as a treatment-specific percentage of ICHs; similarly, their severity distribution, again expressed in terms of mRS, is treatment-specific.

IS and HS survivors are at risk of recurrence: this is modelled according to a real-life registry indicating a cumulative incidence of 4.1 and 3.0 per 100 patient-years, respectively [18]; the severity distribution of recurrent strokes for all alternatives is conditional on the severity of the first stroke, as observed in ARISTOTLE and AVERROES [19].

As with IS and ICH, the model accounts for increasing MI risk with higher ages by applying an HR of 1.30 per decade [20]. MI case fatality rates applied in the simulation are specific for gender (10.8% in men and 15.6% for women), differently than for SE (9.4%) [21].

During the simulation, patients may discontinue treatment, either completely, or by switching to another AC regimen, as a consequence of clinical events incurred, or for other reasons as described on Dorian et al. [10] and Lip et al. [11]

Besides the already described case fatality rates for stroke, bleeding, and MI, the population is subjected to a background mortality derived from ARISTOTLE for the duration of the trial follow-up; given the lack of sound comparative mortality rates, the same background mortality has been applied to all NOACs.

Beyond the trial duration, mortality is projected based on Gompertz distributions fitted on Italian age- and gender-specific population rates [22], corrected for the HRs associated to AF, MI, stroke, and SE, as shown in Table III.

Health condition

NVAF [23]

Stroke [24-26]

MI [27]

SE*

Mild

Moderate

Severe

Female

Male

HR

1.34

3.18

5.84

15.75

4.16

2.56

1.34

Table III. Death hazard ratios according to the health condition of the simulated patient

* Assumption

Costs

Drug

Daily dose (mg/die)

Daily cost (€)

Aspirin

100

0.04

Apixaban

10

1.90

Dabigatran (110 mg)

220

1.90

Dabigatran (150 mg)

300

1.90

Rivaroxaban

20

1.80

Table IV. Drug acquisition costs, at negotiated net prices [28]

Costs are evaluated from the perspective of the National Health System (SSN); accordingly, only direct health care costs are considered:

  • Drug acquisition costs, at negotiated net prices [28] (Table IV);
  • Routine visits [29] for all treated patients;
  • Acute event management (strokes, bleeds, myocardial infarction, and other CV hospitalizations);
  • Long-term post-event management for stroke, MI, and SE;
  • Other health care costs associated with AC management (Table V).

Stroke management costs have been elaborated basing on data reported in an observational study conducted on 411 Italian stroke survivors, followed up for 12 months [30]: for each severity category within ischemic and hemorrhagic strokes, the mean long-term maintenance cost has been approximated to the monthly cost recorded in the second semester; the costs for the acute phase correspond to the sum of the corresponding DRG tariff [31] and the difference between the costs accrued in the first and second follow-up semester.

For acute and long-term MI management, cost data are elaborated basing on three-year follow-up data reported for Italian MI survivors [32]. The costs attributed to the other clinical events considered are equalled to the corresponding DRG-based tariff paid to hospitals by the Italian NHS [31].

Other AC related costs considered are related to dyspepsia management (€ 71.46/year [33], rates of dyspepsia from ARISTOTLE for apixaban and warfarin, from adjusted indirect comparison for dabigatran, and assumed equal to apixaban for rivaroxaban) and to renal function monitoring for dabigatran treated patients at risk (19.4%, according to RELY data), equalled to the corresponding tariff of € 8.16 [31].

All historical cost data have been actualized to 2013 values using official indices [22] (Table V).

Unit cost (€)

Unit

Duration

Source

Routine visit

15.37

per visit

N/A

Lucioni et al. [29]

Ischemic Stroke

Mild

  • Acute

4,663.06

per episode

2 weeks

Fattore et al. [30]

  • Maintenance

81.76

per month

Simulation length

Fattore et al. [30]

Moderate

  • Acute

6,137.96

per episode

2 weeks

Fattore et al. [30]

  • Maintenance

139.04

per month

Simulation length

Fattore et al. [30]

Severe

  • Acute

10,311.34

per episode

2 weeks

Fattore et al. [30]

  • Maintenance

327.95

per month

Simulation length

Fattore et al. [30]

Fatal

3,891.00

per episode

N/A

DRG 14 [31]

Hemorrhagic stroke

Mild

  • Acute

6,321.14

per episode

2 weeks

Fattore et al. [30]

  • Maintenance

118.11

per month

Simulation length

Fattore et al. [30]

Moderate

  • Acute

10,073.43

per episode

2 weeks

Fattore et al. [30]

  • Maintenance

200.86

per month

Simulation length

Fattore et al. [30]

Severe

  • Acute

20,932.42

per episode

2 weeks

Fattore et al. [30]

  • Maintenance

473.77

per month

Simulation length

Fattore et al. [30]

Fatal

3,891

per episode

N/A

DRG 14 [31]

Other ICH

25,812

per episode

N/A

DRG 528 [31]

Other major bleeding

3,317

per episode

N/A

DRG 174 [31]

CRNMB

2,091

per episode

N/A

DRG 175 [31]

IM

  • Acute

6,275.21

per episode

N/A

Mantovani et al. [32]

  • Maintenance

157.97

per month

Simulation length

Mantovani et al. [32]

SE

  • Acute

4,663.06

per episode

2 weeks

Assumption

  • Maintenance

81.76

per month

Simulation length

Assumption

Other CV hospitalization

4,742

per episode

N/A

DRG 479 [31]

Table V. Cost inputs

Budget impact analysis

The budget impact analysis evaluates the financial impact of apixaban introduction by comparing expected 1,2, and 3 years cost in two hypothetical scenarios: with and without apixaban.

Total, undiscounted costs per patient estimated by the simulation for the considered regimens are applied to the corresponding market shares estimated for the two scenarios at 1,2, and 3 years. Numbers of patients for each regimen are estimated by projecting share evolution based on IMS market research [34].

Results

In Table VI, main results of the simulation for all alternatives at 1,2, and 3 years are shown: among available NOACs, it can be seen that apixaban results the least expensive in all considered years.

The target population is estimated in about 364,000 patients (Table VII), calculated by applying a 1.7% AF prevalence rate [35], of which 70% are NVAF subjects, to the Italian resident population, and considering that about 50% satisfy the criteria for reimbursement issued by AIFA, i.e. CHA2DS2-VASc ≥ 1 and HAS-BLED > 3 (9,38%) [36,37], or TTR < 70% (40%) [38] or objective difficulties in measuring INR.

Strategy

Total cost (€)

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

Table VI. Base-case: main simulation results

%

N

Source

Residents in Italy

61,175,388

ISTAT [22]

AF Prevalence

1.70

1,039,982

Bollettino Ufficiale Regione Veneto [35]

NVAF

70

727,987

ESC, 2010 [1]

AIFA criteria*

50

363,994

Friberg, 2012 [36]; ATA-AF, 2013 [37]; Nichol, 2008 [38]

Table VII. Target population per BI

* About 50% of patients satisfy the criteria for reimbursement issued by AIFA: NVAF with both CHA2DS2-VASc ≥ 1 and HAS-BLED > 3, or time in therapeutic range (TTR) < 70% or objective difficulties in measuring INR

It has to be noted that the eligible patient population identified by AIFA through these criteria appears inconsistent with the assigned pharmaceutical expense cap for the class, indicated by AIFA itself in 60 M €/year: it can be easily calculated (basing on an approximate cost of 650 €/year per patient) that this budget is sufficient to cover a maximum of about one fourth of the patients who are expected to benefit the most from the availability of the innovative NOACs.

The expected penetration of NOACs on the market in the next three years has been estimated based on the market evolution from the approval of NVAF as indication for the NOACs (Table VIII); in the scenario in which apixaban is present, an increasing percentage of the NOAC – treated population is prescribed apixaban, with shares subtracted proportionally to the comparators, as shown in Table VIII. Cumulative cost estimates, as estimated by the model and shown in detail in Table VI are applied to the resulting patient numbers for each regimen and added up to obtain the expected budget dedicated to the target population: the budget impact is calculated as the difference among the total costs expected without and with the introduction of apixaban.

Resulting patient numbers per regimen are displayed in Table VIII, alongside the expected cumulative impact: under the detailed assumptions, 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.

Main results of the simulation run on non-experimental population of NVAF patients [13] for all alternatives at 1, 2, and 3 years are presented in Table IX. Resulting expected financial impact obtained by applying these results to the identified target population are displayed in Table X, and substantially confirm the estimates of the base-case analysis.

Year 1

Year 2

Year 3

Common scenario

Target pts (n.)

363,994

363,994

363,994

NOACs

  • n.

71,204

133,481

150,559

  • %

20

37

41

Warfarin

  • n.

292,790

230,513

213,435

  • %

80

63

59

Scenario w/o apixaban

Dabigatran 110 mg (n.)

20,107

36,551

40,654

Dabigatran 150 mg (n.)

25,383

46,144

51,323

Rivaroxaban (n.)

25,714

50,786

58,582

Apixaban (n.)

0

0

0

Scenario w/ apixaban

Dabigatran 110 mg (n.)

9,414

14,093

11,407

Dabigatran 150 mg (n.)

11,884

17,792

14,401

Rivaroxaban (n.)

12,039

19,582

16,437

Apixaban (n.)

37,867

82,014

108,314

BI (€)

-1,180,549

-3,841,429

-5,368,918

Table VIII. Base-case – Budget impact

Regimen

Total cost (€)

Year 1

Year 2

Year 3

Apixaban

1,419

2,942

4,366

Dabigatran (110 mg)

1,441

2,971

4,385

Dabigatran (150 mg)

1,454

2,992

4,413

Rivaroxaban

1,453

3,004

4,445

Table IX. Real world population [13] – main simulation results

Year 1

Year 2

Year 3

Common scenario

Target pts (n.)

363,994

363,994

363,994

NOACs

  • n.

71,204

133,481

150,559

  • %

20

37

41

Warfarin

  • n.

292,790

230,513

213,435

  • %

80

63

59

Scenario w/o apixaban

Dabigatran 110 mg (n.)

20,107

36,551

40,654

Dabigatran 150 mg (n.)

25,383

46,144

51,323

Rivaroxaban (n.)

25,714

50,786

58,582

Apixaban (n.)

0

0

0

Scenario w/ apixaban

Dabigatran 110 mg (n.)

9,414

14,093

11,407

Dabigatran 150 mg (n.)

11,884

17,792

14,401

Rivaroxaban (n.)

12,039

19,582

16,437

Apixaban (n.)

37,867

82,014

108,314

BI (€)

-1.190.296

-3.971.151

-5.568.785

Table X. Real world population [13] – budget impact analysis

A comparison of total costs accruing after three years for the treatment of the whole identified patient population with one of the available NOACs is presented in Table XI, in order to highlight the total potential budget impact of systematically choosing just one of the NOAC for this indication, and to detail how the different cost components are affected by such a choice. 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 per patient saving already shown in Table VI.

Cost (€)

Delta apixaban vs.

Dabigatran (110 mg)

Dabigatran (150 mg)

Rivaroxaban

Anticoagulants

49,632,106

55,842,014

52,540,069

Ischemic Stroke

-24,362,893

-922,257

-365,284

Hemorrhagic Stroke

9,372,101

12,084,733

-3,367,459

Systemic Embolism

-973,544

-1,137,583

-459,840

Other bleedings

-16,016,517

-50,508,295

-73,677,525

MI + CV hospitalizations

-24,207,752

-27,540,021

-2,158,969

Other*

-2,276,000

-2,265,143

206,011

Total cost

-8,832,500

-14,446,551

-27,282,998

Table XI. Potential BI at three years, detailed by component (n. = 363,994)

* Other costs include routine care visit and health care costs associated with AC management

Conclusions

The expected economic differences among NOACs stem from the different safety and effectiveness profile of the NOACs emerging from the adjusted indirect comparison.

Dabigatran, at the 110 mg BID dose, appears associated with a lower ICH risk than apixaban, but this should be traded off with an apparently reduced protection against ischemic strokes; the latter may be mitigated with the higher dabigatran dose (150 mg BID) or with the use of rivaroxaban, but at the expense of much higher bleeding risks; however from a health economics point of view, neither trade-off is expected to be efficient.

In conclusion, analyses based upon demonstrated relative effectiveness and safety profiles indicate that the different balance between ischemic protection and increased bleeding risk is more favourable with apixaban than with the other NOACs from a health economics perspective: the pharmacoeconomic analyses performed and the findings presented in this paper clearly support the value of apixaban in Italian NVAF patients.

Its use in these patients, when compared with other NOACs, is expected to have the potential for relevant savings (between € 8.8 million and € 27.3 million), which are linked to its intrinsic effectiveness and to the lowest discontinuation rate among its class members (it is known that to maintain preventive effectiveness, NOACs have to be taken regularly by the patients).

References

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1 Calculates stroke risk for patients with atrial fibrillation, possibly better than the CHADS2 score. It is composed of 7 domains: age (1 point for ages 65-74, 2 points for > 74); gender (Female, 1 point); congestive heart failure history (yes, 1 point); hypertension history (yes, 1 point); stroke/TIA/thromboembolism history (yes, 2 points), vascular disease history (yes, 1 point), and diabetes mellitus (yes, 1 point).

2 HAS-BLED is an acronym for: Hypertension, Abnormal Liver/Renal Function, Stroke History, Bleeding Predisposition, Labile INR, Elderly (Age > 65), Drugs/Alcohol Usage, with each of the domains scored 1 point if present, to be added up to obtain total score, which correlates with the risk of major bleeding. Estimates risk of major bleeding for patients on anticoagulation to assess risk-benefit in atrial fibrillation care.

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