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Cost Effectiveness of Eplerenone for the Treatment of Systolic Heart Failure with Mild Symptoms in Alberta, Canada

  • Original Research Article
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Abstract

Background

Eplerenone has been demonstrated as being cost effective for the treatment of patients with systolic heart failure (HF) and mild symptoms in several jurisdictions; however, its cost effectiveness is unknown in the context of Alberta, Canada.

Methods

We used a discrete-event simulation model to compare costs and outcomes between standard care and standard care plus eplerenone for the treatment of HF with mild symptoms. We used Alberta data (whenever possible) together with a healthcare perspective, a lifetime horizon, and 3 % annual discount rate for analyses.

Results

Clinically, eplerenone prevented HF hospitalizations, atrial fibrillations, and cardiovascular (CV) deaths, but incurred more adverse events and device implantations than standard care. The remaining life of patients receiving eplerenone was 7.08 versus 5.83 years for those receiving standard care. Eplerenone gained 1.25 life-years and 1.18 quality-adjusted life-years (QALYs), with an incremental cost of $Can7200. Therefore, the incremental cost-effectiveness ratio (ICER) was $Can5700 per life-year gained and $Can6100 per QALY gained.

Conclusions

Given the most cited ICER threshold is $Can50,000, the use of eplerenone as an adjunct to standard care for treating patients with systolic HF and mild symptoms is cost effective in the context of Alberta. Eplerenone would cost the Alberta health system about $Can4.6 million a year in drug costs. Incorporating reductions in health services utilization associated with eplerenone, the budget impact is smaller. For the first year, the use of eplerenone is cost saving and for 5 years the cost is approximately $Can6 million.

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Acknowledgments

Many thanks to Dawn Lee, BresMed, for clarifying the data and assumptions, and to Al Chrosny, TreeAge Software Inc., for supporting the DES model in TreeAge Pro 2015.

Author information

Authors and Affiliations

  1. Institute of Health Economics, 1200-10405 Jasper Ave, Edmonton, AB, T5J 3N4, Canada

    Nguyen X. Thanh

  2. Department of Medicine, University of Alberta, Edmonton, AB, Canada

    Justin A. Ezekowitz & Padma Kaul

  3. School of Public Health, University of Alberta, Edmonton, AB, Canada

    Nguyen X. Thanh & Dat T. Tran

Authors
  1. Nguyen X. Thanh
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  2. Justin A. Ezekowitz
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  3. Dat T. Tran
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  4. Padma Kaul
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Corresponding author

Correspondence to Nguyen X. Thanh.

Ethics declarations

Funding

Financial support was received from Pfizer Canada. Pfizer played no direct role in the study, including the design, analysis, manuscript, or decision to submit for publication.

Conflicts of interest

JA Ezekowitz has received grants, consulting fees, and payments for lectures from Pfizer and the Canadian Institutes of Health Research. NX Thanh, DT Tran, and P Kaul declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Appendices

Appendix 1: Parameters for Time-to-Event (days) Distributions [11, 12]

 

Number of previous hospitalizations*

Distribution

Eplerenone

Standard care

Shape

Scale

Shape

Scale

CV death

0

Weibull

0.82

21612

0.82

1220

 

1

Weibull

0.89

3265

0.89

3447

 

2

Weibull

1.18

2477

1.18

1630

 

3+

Weibull

1.91

1244

1.91

1613

HF hospitalization

0

Weibull

0.77

9006

0.77

4761

 

1

Weibull

0.93

190

0.93

174

 

2

Weibull

1.01

296

1.01

336

 

3

Weibull

0.84

136

0.84

175

 

4

Weibull

1.06

91

1.06

180

 

5

Weibull

1.48

93

1.48

98

 

6

Weibull

1.01

296

1.01

336

 

7

Weibull

0.93

190

0.93

174

 

8+

Weibull

0.77

906

0.77

4761

Other CV hospitalization

0

Weibull

0.72

8895

0.72

6838

 

1

Weibull

1

308

1

343

 

2

Weibull

1.01

296

1.01

336

 

3

Weibull

0.8

151

0.8

307

 

4

Weibull

1.12

287

1.12

71

 

5

Weibull

1.52

110

1.52

41

 

6

Weibull

1

110

1

41

 

7

Weibull

1

308

1

343

 

8+

Weibull

0.72

8895

0.72

6838

Adverse event

0

Weibull

0.62

11920

0.62

17680

 

1+

Weibull

0.93

213

0.93

255

Atrial fibrillation

n/a

Exponential

1

25177

1

14984

Other death

n/a

Exponential

1

33597

1

33597

Device implant

n/a

Exponential

1

12326

1

10933

Discontinuation

n/a

Exponential

1

12315

  
  1. *For adverse event, it is number of previous adverse events

Formula to estimate shape and for the Weibull distributions based on covariance information:

$${\text{Shape }} = e^{{ - { \ln }\left( p \right)}}$$
$${\text{Scale}}_{\text{Eplerenone}} = e^{{\left( { - e^{{ - { \ln }\left( p \right)}} \cdot \left( {{\text{Constant}} + {\text{Eplerenone}}} \right)^{{ - \frac{1}{{e^{{ - { \ln }\left( p \right)}} }}}} } \right)}}$$
$${\text{Scale}}_{\text{Standard Care}} = e^{{\left( { - e^{{ - { \ln }\left( p \right)}} \cdot \left( {\text{Constant}} \right)^{{ - \frac{1}{{e^{{ - { \ln }\left( p \right)}} }}}} } \right)}}$$

Covariance Information

Cardiovascular death:

No previous hospitalizations

Parameter

Coefficient

Constant

Eplerenone

ln(p)

Constant

9.40922

0.06417

−0.00926

0.01641

Eplerenone

0.57180

−0.00926

0.04659

0.00324

ln(p)

0.32673

0.01641

0.00324

0.00587

One previous hospitalization

Constant

8.14534

0.04136

−0.02449

0.01190

Eplerenone

−0.05430

−0.02449

0.05045

−0.00053

ln(p)

0.11399

0.01190

−0.00053

0.00802

Two previous hospitalizations

Constant

7.39649

0.03613

−0.02411

0.01243

Eplerenone

0.41836

−0.02411

0.07479

0.00560

ln(p)

−0.16144

0.01243

0.00560

0.01864

Three previous hospitalizations

Constant

7.38597

0.03306

−0.02947

0.01603

Eplerenone

−0.25983

−0.02947

0.05224

−0.00905

ln(p)

0.22424

0.01603

−0.00905

0.03114

Heart failure hospitalization:

No or eight or more previous hospitalizations

Parameter

Coefficient

Constant

Eplerenone

ln(p)

Constant

8.46827

0.01373

−0.00447

0.00368

Eplerenone

0.63735

−0.00447

0.01770

0.00115

ln(p)

0.26142

0.00368

0.00115

0.00192

One or seven previous hospitalizations

Constant

5.15764

0.01255

−0.01166

−0.00184

Eplerenone

0.09003

−0.01166

0.03310

−4.1E-05

ln(p)

0.07269

−0.00184

−4.1E-05

0.00391

Two or six previous hospitalizations

Constant

5.81586

0.03808

−0.03600

−0.00566

Eplerenone

−0.12714

−0.03600

0.09332

−0.00014

ln(p)

−0.01346

−0.00566

−0.00014

0.01578

Three previous hospitalizations

Constant

5.16306

0.07434

−0.06994

−0.01058

Eplerenone

−0.23199

−0.06994

0.17032

0.00340

ln(p)

0.17713

−0.01058

0.00340

0.01729

Four previous hospitalizations

Constant

5.19425

0.10553

−0.09855

−0.01721

Eplerenone

−0.67973

−0.09855

0.24626

0.00012

ln(p)

−0.06022

−0.01721

0.00012

0.04217

Five previous hospitalizations

Constant

4.58036

0.16466

−0.15729

−0.02975

Eplerenone

−0.04839

−0.15728

0.24645

0.01081

ln(p)

−0.38912

−0.02975

0.01081

0.07635

Other cardiovascular hospitalization:

No or eight or more previous hospitalizations

Parameter

Coefficient

Constant

Eplerenone

ln(p)

Constant

8.83024

0.02330

−0.00937

0.00546

Eplerenone

0.26297

−0.00937

0.02275

0.000564

ln(p)

0.32673

0.00546

0.00056

0.00236

One or seven previous hospitalizations

Constant

6.28276

0.00985

−0.00933

−0.00205

Eplerenone

−0.04146

−0.00933

0.01919

0.00023

ln(p)

−0.42635

−0.00205

0.00023

0.00722

Two previous hospitalizations

Constant

6.54293

0.00771

−0.00723

−0.00240

Eplerenone

−0.16027

−0.00723

0.01901

−0.00063

ln(p)

−0.80976

−0.00240

−0.00063

0.01514

Three previous hospitalizations

Constant

6.52225

0.02387

−0.02236

−0.00762

Eplerenone

−0.05888

−0.02236

0.06035

0.00058

ln(p)

−0.66069

−0.00762

0.00058

0.03537

Four previous hospitalizations

Constant

6.57683

0.13620

−0.13092

−0.02474

Eplerenone

−0.00437

−0.13092

0.22000

−0.00546

ln(p)

−0.66637

−0.02474

−0.00546

0.14173

Five previous hospitalizations

Constant

5.92959

0.03984

−0.03984

2.09E-18

Eplerenone

0.43647

−0.03984

0.06277

−0.02829

ln(p)

−1.61141

2.09E-18

−0.02829

0.26592

Six previous hospitalizations

Constant

5.92959

0.03984

−0.03984

0

Eplerenone

0.43647

−0.03984

0.06277

 

ln(p)

0

   

Adverse event:

No previous adverse events

Parameter

Coefficient

Constant

Eplerenone

ln(p)

Constant

9.78019

0.04347

−0.02069

0.00790

Eplerenone

−0.39420

−0.02069

0.03117

−0.00103

ln(p)

0.48244

0.00790

−0.00103

0.00238

One or more previous adverse event

Constant

5.41534

0.04454

−0.04282

−0.00436

Eplerenone

−0.05508

−0.04282

0.06807

0.00065

ln(p)

0.06899

−0.00436

0.00065

0.00942

Other death:

Parameter

Coefficient

Constant

Eplerenone

Constant

10.4222

0.01923

-

Eplerenone

0

-

-

Atrial fibrillation:

Parameter

Coefficient

Constant

Eplerenone

Constant

9.61470

0.01923

−0.01923

Eplerenone

0.51899

−0.01923

0.05048

Device implantation:

Parameter

Coefficient

Constant

Eplerenone

Constant

9.29952

0.01299

−0.01299

Eplerenone

0.11997

−0.01299

0.02707

Other discontinuation:

Parameter

Coefficient

Constant

Eplerenone

Constant

9.51684

0.01587

−0.01587

Eplerenone

−0.09820

−0.01587

0.02996

Appendix 2: One-way Sensitivity Analysis

 

Variation of ICER

Variable (range)*

From

To

Cost of eplerenone (±30%)

$5,609

$9,521

Scale of Weibull distribution for device, Eplerenone (9852-15458)

$7,696

$4,865

Scale of Weibull distribution for CV hosp, no prev hosp, Eplerenone (6451-12323)

$7,786

$5,120

Scale of Weibull distribution for device, Standard care (8733-13707)

$4,846

$7,301

Scale of Weibull distribution for HF hosp, no prev hosp, Standard care (3781-5972)

$4,982

$7,355

Scale of Weibull distribution for HF hosp, no prev hosp, Eplerenone (6721-12063)

$7,550

$5,217

Scale of Weibull distribution for CV hosp, no prev hosp, Standard care (5085-9235)

$4,993

$7,319

Cost of HF hospitalization (±30%)

$6,670

$5,487

Cost of disease management and monitoring (±30%)

$5,722

$6,435

Cost of concomitant drugs (±30%)

$5,799

$6,358

Cost of Device implantation (±30%)

$5,819

$6,338

Scale of Weibull distribution for other discontinuation (9761-15516)

$5,893

$6,234

Scale of Weibull distribution for AE, no prev AE, Standard care (11693-26499)

$5,922

$6,222

Scale of Weibull distribution for AF, Standard care (11588-19526)

$5,992

$6,198

Scale of Weibull distribution for AE, no prev AE, Eplerenone (8313-17000)

$6,170

$5,992

Probability of discontinuation after AE hospitalization (0.032-0.102)

$6,168

$6,007

Scale of Weibull distribution for AF, Eplerenone (17823-35627)

$6,167

$6,017

Scale of Weibull distribution for CV death, no prev hosp, Standard care (7413-20023)

$6,119

$5,982

Cost of adverse event (±30%)

$6,015

$6,142

Shape of Weibull distribution for CV death, no prev hosp (0.71-0.95)

$6,115

$6,006

Cost of CV hospitalization (±30%)

$6,132

$6,025

Probability of discontinuation after HF hospitalization (0.144-0.258)

$6,130

$6,025

Probability of discontinuation after CV hospitalization (0.059-0.145)

$6,120

$6,037

Scale of Weibull distribution for CV death, no prev hosp, Eplerenone (11890-39174)

$6,013

$6,078

Shape of Weibull distribution for CV hosp, no prev hosp (0.66-0.79)

$6,048

$6,096

Discount rate (0%-5%)

$6,056

$6,083

Shape of Weibull distribution for AE, no prev AE (0.56-0.68)

$6,098

$6,079

Scale of Weibull distribution for other death (26120-43262)

$6,049

$6,032

Shape of Weibull distribution for HF hosp, no prev hosp (0.71-0.84)

$6,104

$6,096

  1. *descending sorted by variation of ICER; AE=adverse event; AF= atrial fibrillation; hosp=hospitalization; prev=previous; CV=cardiovascular; HF=heart failure

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Thanh, N.X., Ezekowitz, J.A., Tran, D.T. et al. Cost Effectiveness of Eplerenone for the Treatment of Systolic Heart Failure with Mild Symptoms in Alberta, Canada. Am J Cardiovasc Drugs 16, 365–376 (2016). https://doi.org/10.1007/s40256-016-0177-0

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