Cost-effectiveness of evolocumab in treatment of heterozygous familial hypercholesterolaemia in Bulgaria: measuring health benefit by effectively treated patient-years*

Figures & data

Figure 1. Evolocumab economic model structure.

CHD, coronary heart disease; CVD, cardiovascular disease; ECVD, established CVD; IS, ischaemic stroke; HF, heart failure; MI, myocardial infarction

Table 1. Patient demographics and baseline characteristics.

Characteristic	HeFH patients (N = 329)
Age, years (SD)	51.16 (12.60)
Female, %	42.25
Current smoking, %	15.81
Type 2 diabetes mellitus, %	7.29
Hypertensive therapy, %	32.52
Acetylsalicylic acid use, %	38.60
Systolic blood pressure, mmHg (SD)	125.73 (13.63)
Body mass index <20 kg/m^2, %	1.82
Mean LDL-C, mg/dL (SD)	155.46 (44.93)
Mean Total-C, mg/dL (SD)	231.56 (48.66)
Mean HDL-C, mg/dL (SD)	51.13 (15.60)
Number of vascular beds*	1.21
Atrial fibrillation*, %	11.70
Previous CVD event (i.e. SP), %	38.30
Initial SP health state, %
ECVD	61.11
Post-MI	25.40
Post-IS	2.38
Post-HF	0.79
Composite health states	10.32
Predicted 10-year risk of CVD events^†	55%

SD, standard deviation; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; SP, secondary prevention; CVD, cardiovascular disease; ECVD, established CVD; IS, ischaemic stroke; HF, heart failure; HeFH, heterozygous familial hypercholesterolaemia; MI, myocardial infarction

* Imputed based on the REACH Registry (Wilson et al. [32]) because of non-availability in RUTHERFORD-2 [18]

^† One or more fatal and non-fatal CVD event

Table 2. CVD event rate ratio per 1 mmol/L (38.67 mg/dL) of LDL-C reduction.

Event	Rate Ratio (99% CI)	Source
ECVD	0.71 (0.58–0.87)	Assumed to be equivalent to MI
MI	0.71 (0.58–0.87)	CTTC [11] Figure 2 (more vs less statin)
IS	0.69 (0.50–0.95)	CTTC [11] Figure 2 (more vs less statin)
CHD death	0.80 (0.76–0.85)	CTTC [12] Webfigure 3 and 8 (overall)
IS death	1.00	Assumed equal to 1 because of statistical non-significance (1.04; 95% CI: 0.77–1.41) [11]
Revascularisation*	0.66 (0.60–0.73)^†	CTTC [11] Figure 2 (more vs less statin)

CI, confidence interval; ECVD, established cardiovascular disease; IS, ischaemic stroke; CHD, coronary heart disease; CTTC, Cholesterol Treatment Trialists’ Collaboration; MI, myocardial infarction

* Defined as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)

† Denoting a 95% CI

Figure 2. Univariate sensitivity analyses.

CVD, cardiovascular disease; ECVD, established CVD; HeFH, heterozygous familial hypercholesterolaemia; LDL-C, low-density lipoprotein cholesterol; MI, myocardial infarction

Table 3. CVD event costs per patient per year.

	Annual direct cost (BGN)
Modelled health state	Acute (year 1)	Post-event (subsequent years)	Source
No CVD	0.00	–	Assumption
ECVD*	–	582.05	[47,50]
MI	7,384.10	582.05	[47,50]
IS	4,154.84	223.03	[47,50]
HF	2,569.28	2,564.61	[47,50]
CHD death	5,171.50	–	[47,50]
28.3% Fatal UA	5,270.00
56.6% Fatal MI	6,380.00
15% Fatal HF	420.00
IS death	8,095.00	–	[47,50]
Non-CVD death	0.00	–	Assumption
Revascularisation	5,498.92	–	[47,50]
78.5% PCI	4,238.00
21.5% CABG	10,100.00

CABG, coronary artery bypass grafting; CVD, cardiovascular disease; ECVD, established CVD; IS, ischaemic stroke; HF, heart failure; CHD, coronary heart disease; UA, unstable angina; MI, myocardial infarction; HF, heart failure; MI, myocardial infarction; PCI, percutaneous coronary intervention

* Assumed to be equivalent to the costs attributed to subsequent years of MI (BGN 582.05)

Table 4. Predicted CVD event rates, ETPYs and costs.

	Evolocumab + SoC	SoC alone	Increment (∆)
Total LYs*	12.07	11.15	0.93
Total ETPYs*	9.52	0.22	9.30
CVD events	1.81	2.92	−1.11
MI	0.72	1.63	−0.92
IS	0.11	0.26	−0.16
HF	0.44	0.36	0.08
Fatal CVD	0.54	0.65	−0.11
Revascularisation	0.65	1.65	−1.00
Costs (BGN)
Total cost	139,741	19,412	120,329
Medication	128,592	1,432	127,160
Non-fatal acute CVD events	3,239	7,088	−3,849
Fatal CVD events	1,201	1,545	−344
Revascularisation	1,866	4,862	−2,995
Post-event	3,480	3,381	99
ICER (BGN/ETPY gained)			12,937
Probabilistic sensitivity analysis results
Mean ETPY	9.51	0.22	9.29
Mean cost (BGN)	139,853	19,400	120,454
ICER (BGN/ETPY gained)			12,963

SoC, standard of care; LYs, life-years; ETPYs, effectively treated patient-years; CVD, cardiovascular disease; IS, ischaemic stroke; HF, heart failure; ICER, incremental cost-effectiveness ratio; MI, myocardial infarction

* Discounted

Wilson PWF, D’Agostino R, Bhatt DL, et al. An international model to predict recurrent cardiovascular disease. Am J Med. 2012;125:695–703.

 PubMed Web of Science ®Google Scholar

Raal FJ, Stein EA, Dufour R, et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385:331–340.

 PubMed Web of Science ®Google Scholar

Cholesterol Treatment Trialists Collaboration (CTTC). Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. Elsevier Ltd. 2010;376:1670–1681.

 Web of Science ®Google Scholar

Cholesterol Treatment Trialists Collaboration (CTTC). The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–590.

 Web of Science ®Google Scholar

National Health Insurance Fund (Национална Здравноосигурителна Каса [НЗОК]). Ordinance No. 10 from 24. 03.2009 for the conditions and order for payment of medicinal products under article 262, al 6, p. 1 and p. 2 [Internet]. [cited 2016 Jan 13]. Available from: http://www.nhif.bg/web/guest/67

 Google Scholar

National Health Insurance Fund (Национална Здравноосигурителна Каса [НЗОК]). Ordinance No. 40 from 24. 11. 2004 for defining the basic package of healthcare activities, guaranteed by the budget of NHIF [Internet]. [cited 2016 Jan 13]. Available from: http://www.nhif.bg/web/guest/67

 Google Scholar