Economic evaluation of ezetimibe treatment in combination with statin therapy in the United States

Figures & data

Figure 1. Model schematic. CVD, cardiovascular disease.

Table 1. Characteristics of patients identified from PMTX + claims and EMR databases.

Characteristic	n = 548
Age (years), mean ± SD	57.8 ± 8.0
Male patients, n (%)	304 (55.5)
LDL-C level (mg/dL), mean ± SD	94.55 ± 21.0
Current smoker, n (%)	104 (19.0)
Comorbidity, n (%)
Hypertension	394 (71.9)
Diabetes	195 (35.6)
History of stroke	189 (34.5)
History of PAD	108 (19.7)
History of CHF	0
History of AF	41 (7.5)
Statin and dose, n (%)
Atorvastatin 10 mg	45 (8.2)
Atorvastatin 20 mg	61 (11.1)
Atorvastatin 40 mg	71 (13.0)
Atorvastatin 80 mg	36 (6.6)
Simvastatin 10 mg	34 (6.2)
Simvastatin 20 mg	78 (14.2)
Simvastatin 40 mg	84 (15.3)
Simvastatin 80 mg	15 (2.7)
Rosuvastatin 5 mg	22 (4.0)
Rosuvastatin 10 mg	44 (8.0)
Rosuvastatin 20 mg	35 (6.4)
Rosuvastatin 40 mg	23 (4.2)

AF: atrial fibrillation; CHF: congestive heart failure; LDL-C: low-density lipoprotein cholesterol; EMR: Electronic Medical Record; PAD: peripheral artery disease; PMTX+: IMS Health’s PharMetrics Plus Health Plan Claims database; SD: standard deviation.

Table 2. Model parameters for base-case scenario and one-way sensitivity analyses.

Parameter		One-way sensitivity			Source
Parameter group	Specific parameter	Base	Minimum	Maximum
LDL-C lowering efficacy	Ezetimibe added	−0.234	−0.244	−0.225	—
Rate reductions (Relative Risk)	For fatal CHD	0.81	0.75	0.87	Ara et al.^36
	For non-fatal CHD	0.74	0.70	0.79	Ara et al.^36
	For fatal stroke	0.91	0.74	1.11	Ara et al.^36
	For non-fatal stroke	0.83	0.78	0.88	Ara et al.^36
Cost: primary (2013 US Dollars; $)	No event	783.00	626.40	939.60	Pandya et al.^24
	Non-CVD death	0.00	0.00	0.00	Pandya et al.^24
	Fatal CHD	17,259.00	13,807.20	20,710.80	Pandya et al.^24
	Fatal stroke	10,647.00	8,517.60	12,776.40	Pandya et al.^24
	Acute CHD	62,200.00	49,760.00	74,640.00	Pandya et al.^24
	Acute stroke	20,509.00	16,407.20	24,610.80	Pandya et al.^24
Cost: history of CHD (2013 US Dollars; $)	No event	3,201.00	2,560.80	3,841.20	Pandya et al.^24
	Non-CVD death	0.00	0.00	0.00	Pandya et al.^24
	Fatal CHD	17,259.00	13,807.20	20,710.80	Pandya et al.^24
	Fatal stroke	10,647.00	8,517.60	12,776.40	Pandya et al.^24
	Acute CHD	62,200.00	49,760.00	74,640.00	Pandya et al.^24
	Acute stroke	20,509.00	16,407.20	24,610.80	Pandya et al.^24
Cost: history of stroke (2013 US Dollars; $)	No event	2,115.00	1,692.00	2,538.00	Pandya et al.^24
	Non-CVD death	0.00	0.00	0.00	Pandya et al.^24
	Fatal CHD	17,259.00	13,807.20	20,710.80	Pandya et al.^24
	Fatal stroke	10,647.00	8,517.60	12,776.40	Pandya et al.^24
	Acute CHD	62,200.00	49,760.00	74,640.00	Pandya et al.^24
	Acute stroke	20,509.00	16,407.20	24,610.80	Pandya et al.^24
Cost: history of CHD and stroke (2013 US Dollars; $)	No event	3,201.00	2,560.80	3,841.20	Pandya et al.^24
	Non-CVD death	0.00	0.00	0.00	Pandya et al.^24
	Fatal CHD	17,259.00	13,807.20	20,710.80	Pandya et al.^24
	Fatal stroke	10,647.00	8,517.60	12,776.40	Pandya et al.^24
	Acute CHD	62,200.00	49,760.00	74,640.00	Pandya et al.^24
	Acute stroke	20,509.00	16,407.20	24,610.80	Pandya et al.^24
Utility weights	Acute CHD	0.770	0.62	0.92	Ara et al.^36
	Acute stroke	0.629	0.50	0.75	Ara et al.^36
	Stable CHD	0.847	0.68	1.00	Ara et al.^36
	Stable stroke	0.692	0.55	0.83	Ara et al.^36

Ara et al.³⁶; Pandya et al.²⁴.

CHD: coronary heart disease; CVD: cardiovascular disease; LDL-C: low-density lipoprotein cholesterol.

Table 3. Costs of statin treatments.

Statin	Dose (mg)	WAC/day (US Dollars; $)
Atorvastatin	10	0.37
	20	0.52
	40	0.52
	80	0.52
Simvastatin	10	0.18
	20	0.19
	40	0.19
	80	0.19
Rosuvastatin	5	8.28
	10	8.28
	20	8.28
	40	8.28

Data were obtained from First DataBank, and reflect published catalog or list price as of October 5, 2015.

WAC: wholesale acquisition cost.

Figure 2. Total fatal cardiovascular disease for all patients with LDL-C levels ≥70 mg/dL (n = 548). LDL: low-density lipoprotein.

Figure 3. Total cardiovascular events (fatal and non-fatal) for all patients with LDL-C levels ≥70 mg/dL (n = 548). CVD: cardiovascular disease; LDL: low-density lipoprotein.

Table 4. ICER summary for base-case analysis of patients with a history of ASCVD and LDL-C levels ≥70 mg/dL.

Parameter	Base statin	Ezetimibe combined with statin	Incremental
Treatment cost	3,170.27	10,344.20	7,173.93
Event cost	96,824.45	91,181.02	–5,643.44
Total costs	99,994.72	101,525.22	1,530.50
Life years	15.67	15.87	0.20
QALYs	11.63	11.80	0.17
ICER			9,149

All costs are in US dollars.

ASCVD: atherosclerotic cardiovascular disease; ICER: incremental cost-effectiveness ratio; LDL-C: low-density lipoprotein cholesterol; QALY: quality-adjusted life year.

Table 5. One-way sensitivity analysis for patients with a history of ASCVD and LDL-C levels ≥70 mg/dL (n = 548).

Parameter group	Specific parameter	Incremental cost of combination ezetimibe/statin vs base statin therapy
		Low	High
LDL-C level lowering efficacy	Statin	9,149	9,149
	Ezetimibe combined with statin	7,400	10,857
Rate reductions	Fatal CHD	8,817	9,680
	Non-fatal CHD	3,413	16,514
	Fatal stroke	9,051	9,316
	Non-fatal stroke	8,119	10,250
	Costs	15,895	2,402
Utility weights	Acute CHD	8,500	9,905
	Acute stroke	9,065	9,229
	Stable CHD	12,609	7,310
	Stable stroke	9,521	8,813
Baseline risk adjustments	Non-fatal CHD	28,194	−28,332
	Fatal CHD	7,610	10,308
	Non-fatal stroke	10,914	5,913
	Fatal stroke	8,786	9,791
—	Allocation for CVD death	9,238	9,068
—	Ezetimibe price reduction of 95% to 80%	−3,645	34,735

All costs are in US dollars.

ASCVD: atherosclerotic cardiovascular disease; CHD: coronary heart disease; CVD: cardiovascular disease; LDL-C: low-density lipoprotein cholesterol.

Table 6. ICER summary for sub-group analyses of patients with LDL-C levels ≥100 mg/dL and patients diagnosed with diabetes mellitus with LDL-C levels ≥70 mg/dL.

Parameter	Patients with LDL-C levels ≥100 mg/dL			Patients with diabetes mellitus and LDL-C levels ≥70 mg/dL
	Base statin therapy	Ezetimibe combined with statin	Incremental	Base statin therapy	Ezetimibe combined with statin	Incremental
Treatment cost	2,852.28	10,128.69	7,276.41	2,982.85	9,841.84	6,858.99
Event cost	97,860.37	90,761.59	−7,098.78	104,549.66	97,813.44	−6,736.22
Total costs	100,712.65	100,890.28	177.63	107,532.50	107,655.28	122.78
Life years	15.94	16.20	0.25	14.47	14.74	0.27
QALYs	11.82	12.04	0.21	10.67	10.89	0.22
ICER			839			560

All costs are in US dollars.

ICER: incremental cost-effectiveness ratio; LDL-C: low-density lipoprotein cholesterol; QALY: quality-adjusted life year.

Table 7. One-way sensitivity analyses of patient sub-groups.

Parameter group	Specific parameter	Incremental cost of combination ezetimibe/statin vs base statin therapy
		Patients with LDL-C levels ≥100 mg/dL (n = 179)		Patients with diabetes mellitus and LDL-C levels ≥70 mg/dL (n = 195)
		Low	High	Low	High
LDL-C level lowering efficacy	Statin	839	839	560	560
	Ezetimibe combined with statin	−557	2,203	−711	1,803
Rate reductions	Fatal CHD	2,075	−1,132	2,138	−1,965
	Non-fatal CHD	−4,766	8,041	−4,811	7,474
	Fatal stroke	1,915	–979	1,903	−1,714
	Non-fatal stroke	78	1,655	−193	1,363
	Costs	7,546	−5,868	6,708	−5,588
Utility weights	Acute CHD	780	908	524	603
	Acute stroke	831	847	556	564
	Stable CHD	1,156	671	766	450
	Stable stroke	873	809	589	535
Baseline risk adjustments	Non-fatal CHD	19,400	−35,714	17,955	−33,438
	Fatal CHD	−4,206	4,441	−5,461	4,896
	Non-fatal stroke	2,273	−1,877	1,896	−1,997
	Fatal stroke	336	1,731	0	1,563
—	Allocation for CVD death	594	1,069	237	862
—	Ezetimibe price reduction  of 95% to 80%	−9,497	21,510	−8,471	18,622

All costs are in US dollars.

CHD: coronary heart disease; CVD: cardiovascular disease; LDL-C: low-density lipoprotein cholesterol.

Ara R, Pandor A, Stevens J, et al. Early high-dose lipid-lowering therapy to avoid cardiac events: a systematic review and economic evaluation. Health Technol Assess 2009;13:1-74, 75-118

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Pandya A, Sy S, Cho S, et al. Cost-effectiveness of 10-year risk thresholds for initiation of statin therapy for primary prevention of cardiovascular disease. JAMA 2015;314:142-50

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