A novel cost-effectiveness model of prescription eicosapentaenoic acid extrapolated to secondary prevention of cardiovascular diseases in the United States

Figures & data

Table 1. Base case input parameters: clinical events.

Parameter						Source(s)
Event, % experiencing over 5 years	EPA-plus-statin therapy		Statin monotherapy
Sudden cardiac death	0.7		2.0			JELIS^5; PROVE-IT-TIMI 22^23
Fatal MI	0.3		1.0			JELIS^5; Assumption*
Nonfatal MI	1.4		4.9			JELIS^5; TNT^22
Unstable angina	4.8		7.5			JELIS^5; Assumption†
CABG/PTCA	7.0		10.0			JELIS^5; CTT^19
Stroke	1.9		3.0			JELIS^5; CTT^19
Distribution of CABG vs PCTA, %
CABG	35					FREEDOM^24; SYNTAX^25
PCTA	65
Distributions of events over time, % per year
Year	1	2	3	4	5
CABG/PCTA	33.3	33.3	11.1	11.1	11.1	FREEDOM^24; SYNTAX^25; expert opinion, guided by literature
Other MACCE	20	20	20	20	20	Expert opinion, guided by literature

* Assumption based on expert opinion and values calculated from Dieleman et al.²⁶ for non-Japanese population.

† Assumption based on values reported for PROVE-IT-TIMI 22²³ extrapolated to 5 years and corrected to reflect improved medical management.

CABG, coronary artery bypass grafting; CTT, Cholesterol Treatment Trialists’ Collaboration; EPA, eicosapentaenoic acid; FREEDOM, Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease; JELIS, Japan Eicosapentaenoic Acid Lipid Intervention Study; MACCE, major adverse cardiovascular and cerebrovascular events; MI, myocardial infarction; PROVE-IT-TIMI 22, Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22; PTCA, percutaneous transluminal coronary angioplasty; SYNTAX, Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery; TNT, Treating to New Targets study.

Table 2. Base case input parameters: costs.

Parameter	Annual per-patient cost (USD)*	Source(s)
Sudden cardiac death	$34,501	Russell et al.^30, 1998
Fatal MI	$34,501	Russell et al.^30, 1998
Non-fatal MI	$47,139	Wang et al.^31, 2013; Azoulay et al.^32, 2003
Subsequent non-fatal MI	$3,446	Applies ratio from Cowie et al.^33, 2011
Unstable angina	$33,935	Kongnakorn et al.^34, 2009; Russell et al.^30, 1998
Subsequent unstable angina	$3,875	Bloom et al.^35, 1999
CABG	$48,050	Osnabrugge et al.^36, 2014; Brown et al.^37, 2008; Wang et al.^31, 2013; Magnuson et al.^24, 2013; Eisenberg et al.^38, 2005; Cohen et al.^25, 2014
PTCA	$27,363	Magnuson et al.^24, 2013; Cohen et al.^25, 2014
Subsequent revascularization	$5,183	Cohen et al.^25, 2014
Stroke	$67,383	Kongnakorn et al.^34, 2009
Subsequent stroke	$15,147	Applies ratio from Cowie et al.^33, 2011
US EPA (icosapent ethyl): 12•WAC	$2,504	Medispan – PriceRx 1/21/2015
Statins (annual)	$1,000	Assumption^†

* Costs were inflated to 2014 values and discounted 3%/year as described in the Methods.

† Statin costs were an approximation and blended from generic and brand costs³⁹ and can be changed in the model.

CABG, coronary artery bypass grafting; EPA, eicosapentaenoic acid; MI, myocardial infarction; PTCA, percutaneous transluminal coronary angioplasty; USD, United States dollars; WAC, wholesale acquisition cost.

Table 3. Base case input parameters: utilities.

Parameter	Value	Source(s)
Baseline utility	0.7800	Luengo-Fernandez et al.^40, 2013
Year with non-fatal MI or revascularization	0.6864	McConnachie et al.^41, 2014 (based on 24% decrement for half year)
Year(s) following non-fatal MI or revascularization	0.7332	Assumption: midpoint of baseline and event year*
Year with unstable angina	0.7059	McConnachie et al.^41, 2014 (based on 19% decrement for half year)
Year(s) following unstable angina	0.7332	Assumption: midpoint of baseline and event year*
Year with stroke	0.6353	McConnachie et al.^41, 2014 (based on 37.1% decrement for half year)
Year(s) following stroke	0.7077	Assumption: midpoint of baseline and event year*

MI, myocardial infarction.

* The model assumes that patients’ utility values increase halfway back to baseline (i.e. the midpoint value between the utility during the event year and the baseline utility).

Figure 1. Decision analytic model flow.

Table 4. Model results: base case.

	EPA-plus-statin therapy	Statin monotherapy
First year costs* and outcomes
Pharmacologic agents	$3,497	$994
Costs of MACCE	$1,547	$2,666
Utilities	0.775	0.771
Second year costs* and outcomes
Pharmacologic agents	$3,386	$958
Costs of MACCE	$1,886	$4,020
Utilities	0.748	0.740
Third year costs* and outcomes
Pharmacologic agents	$3,277	$924
Costs of MACCE	$1,328	$5,422
Utilities	0.724	0.713
Fourth year costs* and outcomes
Pharmacologic agents	$3,173	$891
Costs of MACCE	$4,020	$6,452
Utilities	0.700	0.686
Fifth year costs* and outcomes
Pharmacologic agents	$3,071	$859
Costs of MACCE	$4,191	$7,401
Utilities	0.679	0.665
5 year totals
Total cost*	$29,377	$30,587
Total utilities	3.627	3.575
Incremental cost-effectiveness ratio	EPA-plus-statin dominates statin monotherapy

* All costs are per patient. EPA, eicosapentaenoic acid; MACCE, major adverse cardiovascular and cerebrovascular events.

Table 5. Modeled sensitivity analyses.

Scenario and/or changes from base case	Cost/QALY
Base case	EPA plus statin dominates statin monotherapy
Vary event rates
JELIS scenario	$210,294/QALY; EPA is not cost-effective
Alternate scenario*	EPA plus statin dominates statin monotherapy
Sudden cardiac death event rate 0.7% for both EPA plus statin and statin only	EPA plus statin dominates statin monotherapy
Fatal MI event rate 0.4% for both EPA plus statin and statin only	EPA plus statin dominates statin monotherapy
For non-fatal MI, statin-only event rate 2%	$52,938/QALY; EPA is cost-effective with intermediate value†
For CABG/PTCA, statin-only event rate 8%	$12,070/QALY; EPA is cost-effective with high value†
Sudden cardiac death event rate 0.7% and fatal MI event rate 0.4% for both EPA plus statin and statin only	EPA plus statin dominates statin monotherapy
Sudden cardiac death event rate 0.7% and fatal MI event rate 0.4% for both EPA plus statin and statin only, event rate for non-fatal MI 3% for statin only	$100,357/QALY; EPA is cost-effective with intermediate value
Sudden cardiac death event rate 0.7%, fatal MI event rate 0.4%, and stroke rate 1.9% for both EPA plus statin and statin only, event rate for non-fatal MI 3% for statin only	$202,078/QALY; EPA is not cost-effective
CABG vs PTCA: all events CABG or all events PTCA	EPA plus statin dominates statin monotherapy
Vary timing of events
CABG: evenly distributed over 5 years	EPA plus statin dominates statin monotherapy
CABG: back-loaded (15% in each of first 2 years, evenly distributed afterward)	$798/QALY; EPA is cost-effective with high value†
MI: back-loaded (15% in each of first 2 years, evenly distributed afterward)	EPA plus statin dominates statin monotherapy
Vary costs
Discount rate: varies from 0% to 5%	EPA plus statin dominates statin monotherapy
Costs: varied by 25% above or below base case	EPA plus statin dominates statin monotherapy
Statin cost: decreased to $150 annually or increased to $2,000 annually	EPA plus statin dominates statin monotherapy
Vary inputs: utilities
Utilities: varied by 10% above or below base case	EPA plus statin dominates statin monotherapy

* Alternate scenario: statin-only group having ∼2–3.5× higher event rates than the EPA plus statin group; scenario influenced by well-controlled outcome trials (CTT¹⁹, TNT²², PROVE-IT–TIMI 22²³).

† Results were interpreted based on the joint ACC/AHA statement on cost/value methodology⁴².

ACC/AHA, American College of Cardiology/American Heart Association; CABG, coronary artery bypass grafting; EPA, eicosapentaenoic acid; JELIS, Japan Eicosapentaenoic Acid Lipid Intervention Study; MI, myocardial infarction; PTCA, percutaneous transluminal coronary angioplasty; QALY, quality-adjusted life year.

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