Cost-effectiveness of edoxaban compared to warfarin for the treatment and secondary prevention of venous thromboembolism in the UK

Figures & data

Figure 1. Structure of the Markov model.

Table 1. Efficacy and safety inputs of edoxaban vs. warfarin, from the Hokusai-VTE clinical trial.

Parameter	Base case value [DSA range]
Odds Ratio (OR) of edoxaban vs. warfarin	First six months	Following months
VTE recurrence	0.83 [0.59–1.17]*	0.82 [0.25–2.68]*
CRNMB	0.78 [0.66–0.93]	0.89 [0.59–1.32]*
Non-ICH MB	1.15 [0.75–1.75]*	0.44 [0.13–0.42]
ICH	0.23 [0.07–0.81]	0.39 [0.08–2.02]*
Baseline monthly probabilities (event rate in warfarin arm)	First six months	Following months
VTE recurrence	1.8% [1.4–2.2%]	0.2%[0.0–0.4%]
CRNMB	1.7%[1.4–2.0%]	0.4%[0.2–0.6%]
Non-ICH MB	0.16%[0.07–0.26%]	0.04%[0.00–0.10%]
ICH	0.03%[0.00–0.08%]	0.03%[0.00–0.08%]

*Odds-ratios which were set to 1 in the scenario analysis. DSA: Deterministic sensitivity analysis, OR: Odds-ratio, VTE: Venous Thromboembolism, CRNMB: Clinically relevant non major bleeding, ICH: Intracranial haemorrhage.

Table 2. Inputs for the base case analysis and ranges of values used for the deterministic sensitivity analysis.

Parameter	Base case value [DSA range]
Clinical parameters
Proportion of PE in index events [8]	40.1% [39.1–41.2%]
Proportion of PE with also DVT in index events [8]	44.1% [42.4–45.8%]
Proportion of PE among VTE recurrences [8]	56.5% [50.7–62.4%]
Probability of VTE recurrence while off treatment [10]	0.42% [0.36–0.49%]
Probability of developing CTEPH after a PE [10]	4.8% [2.3–9.6%]
Probability of developing PTS after a DVT [11]	2.7% [2.7–8.1%]
Probability to become disable after ICH event [12]	65% [56–75%]
Death after PE recurrence [13]	6.1% [3.0–30.8%]
Death after non-ICH MB [8]	6.1% [1.4–10.8%]
Death after ICH [8]	26.1% [8.1–44.0%]
Death after pulmonary endarterectomy (CTEPH) [15]	4.4% [2.6–6.2%]
Long-term monthly mortality post-ICH [14]	3.3% [1.4–3.3%]
Long-term monthly mortality post-CTEPH [16]	0.7% [0.6–0.7%]
Utility parameters
Utility PE [20]	0.67 [0.30–0.72]
Utility DVT [20]	0.71 [0.54–0.80]
Utility decrement with warfarin (vs. edoxaban) [21]	1.4% [0.0–1.9%]
Utility decrement due to CRNMB [22]	5% [0–10%]
Utility decrement due to Non-ICH MB [22]	32% [9–48%]
Utility decrement due to ICH [22]	65% [44–85%]
Utility decrement due to disability following ICH [22]	65% [44–85%]
Utility decrement due to CTEPH [23]	30% [26–34%]
Utility decrement due to PTS [22]	14% [0–31%]
Resource use & economic parameters
Anticoagulant treatment and heparin
Warfarin monthly costs (£) (eMIT)	1.22
Edoxaban monthly costs (first/subsequent) (£)	44.5/53.3
Heparin daily cost (incl. administration costs) (£) (BNF)	12.8 [7.9–15.5]
Days of heparin lead-in with warfarin/edoxaban	6.5 [5.0–8.5]/5.0 [5.0–7.5]
INR Monitoring while on warfarin
Cost INR visit First/Subsequent (£) [24]	87 [42–92]/26 [16–37]
INR visits for titration	4.0 [3.0–6.0]
Monthly INR visits (after 1st month)	1.0 [0.8–1.7]
VTE event costs
Costs per PE event (£) [24]	1,647 [1,238–3,668]
Cost per DVT event [24]	551 [654–1,086]
Costs due to Bleeding Complications (£)
Monthly costs for disabled ICH	524 [164–1,053]
Inpatient cost due to ICH [24]	3,012 [1,964–6,493]
Non-ICH MB (inpatient) [24]	2,940 [2,330–5,610]
CRNMB (inpatient + outpatient) [24]	384 [308–461]
CTEPH & PTS
Monthly PTS costs (First/Subsequent) (£) [24]	168 [167–173]/23 [23–24]
Cost of Pulmonary endarterectomy (£) [24]	7,824 [6,540–10,227]
% CTEPH patients undergoing endarterectomy [28]	50% [40–60%]
Monthly drug costs (£) (BNF)	1,348[1,078–1,617]

DSA: Deterministic sensitivity analysis, PE: Pulmonary embolism, DVT: Deep venous thrombosis, VTE: Venous thromboembolism, CTEPH: Chronic thromboembolic pulmonary hypertension, PTS: Severe post-thrombotic syndrome, MB: Major bleeding, CRNMB: Clinically relevant non major bleeding, INR: International normalised ratio, BNF: British National Formulary.

Table 3. Model results for base-case and subgroups analysis.

	1. Base case analysis, VTE population		2. Subgroup analyses
			(a) Index DVT only		(b) Index PE (± DVT)		(c) Index PE – DVT		(d) Index PE + DVT
	Edoxaban	Warfarin	Edoxaban	Warfarin	Edoxaban	Warfarin	Edoxaban	Warfarin	Edoxaban	Warfarin
Clinical outcomes (cumulative incidence over the time horizon)
VTE recurrence	105.53%	105.56%	124.42%	124.20%	83.77%	84.04%	86.15%	86.42%	78.54%	78.84%
CRNMB	13.85%	15.53%	13.51%	15.38%	14.63%	16.02%	16.41%	18.38%	11.41%	11.50%
Non-ICH MB	4.74%	4.62%	2.09%	2.15%	3.88%	3.50%	5.29%	4.62%	1.12%	1.32%
ICH MB	1.83%	2.09%	0.45%	0.74%	3.84%	4.07%	2.94%	3.25%	5.55%	5.66%
PTS	4.07%	4.07%	4.09%	4.08%	2.22%	2.22%	0.55%	0.55%	4.84%	4.85%
CTEPH	4.70%	4.70%	3.45%	3.45%	7.54%	7.55%	7.93%	7.94%	7.06%	7.06%
Specific Death	4.17%	4.29%	2.38%	2.51%	7.40%	7.51%	7.26%	7.40%	7.81%	7.87%
Health outcomes
Life years	16.523	16.494	16.678	16.645	16.169	16.143	16.141	16.109	16.186	16.170
QALYs	1.846	1.842	0.546	0.538	3.299	3.321	3.238	3.259	3.387	3.414
On treatment	10.703	10.677	12.347	12.322	8.696	8.642	8.732	8.674	8.623	8.571
Off treatment	0.040	0.040	0.046	0.046	0.034	0.034	0.034	0.034	0.032	0.032
Recurrent VTE	0.008	0.004	0.006	0.005	0.013	0.000	0.014	0.003	0.011	−0.006
Adverse Events	−0.101	−0.099	−0.082	−0.081	−0.119	−0.117	−0.102	−0.101	−0.148	−0.146
Complications (PTS & CTEPH)	1.846	1.842	0.546	0.538	3.299	3.321	3.238	3.259	3.387	3.414
Total QALYs	12.497	12.464	12.862	12.831	11.923	11.880	11.917	11.870	11.905	11.865
Costs
Treatment costs (excluding INR monitoring)	£392	£90	£392	£90	£392	£90	£391	£90	£394	£90
INR monitoring	£0	£323	£0	£323	£0	£323	£0	£323	£0	£324
Recurrent VTE (acute & treatment)	£2,045	£2,049	£1,252	£1,250	£3,063	£3,091	£3,101	£3,128	£3,016	£3,048
CRNMB	£71	£77	£39	£46	£131	£137	£123	£131	£147	£149
Non ICH MB	£92	£89	£51	£53	£82	£70	£109	£89	£27	£33
ICH (acute and long term costs)	£98	£124	£33	£62	£197	£220	£150	£180	£286	£295
Complications (PTS & CTEPH)	£4,439	£4,439	£2,431	£2,427	£7,985	£7,994	£8,168	£8,177	£7,785	£7,797
Total costs	£7,136	£7,191	£4,198	£4,252	£11,850	£11,925	£12,042	£12,118	£11,656	£11,736
Cost-effectiveness analysis
Incremental QALYs	0.033		0.031		0.043		0.046		0.046
Incremental costs	-£55		-£54		-£74		-£76		-£81
Cost per QALY gained (ICER)	Dominant		Dominant		Dominant		Dominant		Dominant
Net Monetary Benefit	£717		£680		£939		£1,005		£880

PE: Pulmonary embolism, DVT: Deep venous thrombosis, VTE: Venous thromboembolism, CTEPH: Chronic thromboembolic pulmonary hypertension, PTS: Severe post-thrombotic syndrome, MB: Major bleeding, CRNMB: Clinically relevant non major bleeding, INR: International normalised ratio, ICER: Incremental cost-effectiveness ratio.

Figure 2. Deterministic sensitivity analysis of the cost effectiveness of edoxaban vs. warfarin (the 10 most impactful parameters are shown).

Figure 3. Incremental cost-effectiveness plane (a) and cost-effectiveness acceptability curve (b) of edoxaban vs. warfarin (n = 2,000 simulations).

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