Setting priorities in the health care sector – the case of oral anticoagulants in nonvalvular atrial fibrillation in Denmark

Figures & data

Table 1 Risk reduction in stroke and bleeding events* using NOACs compared with warfarin

RCT study data	Stroke	Intracranial bleeding	Gastrointestinal bleeding	Other bleedings
Dabigatran (Connolly et al, 2009)^Citation8
1-year event risk among warfarin patients	1.69%	0.74%	1.02%	1.60%
Relative risk (HR) in events using dabigatran 110 mg/150 mg compared with warfarin (CI)	1.00**/0.66 (NS: 0.91; CI: 0.74–1.11/0.66; CI: 0.53–0.82)	0.31/0.40 (0.31; CI: 0.20–0.47/0.40; CI: 0.27–0.60)	1.00**/1.50 (NS: 1.10; CI:0.86–1.41/1.50; CI: 1.19–1.89)	1.00**/1.00** (0.85; CI: NA/0.83; CI: NA)
Rivaroxaban (Patel et al, 2011)^Citation9
1 year event risk among warfarin patients	2.40%	0.73%	1.33%	1.28%
Relative risk (HR) in events using rivaroxaban compared with warfarin (CI)	1.00** (0.88; CI: 0.75–1.03)	0.67 (CI: 0.30–0.58)	1.45 (CI: NA)	1.00 (0.78; CI: NA)
Apixaban (Granger et al, 2011)^Citation10
1 year event risk among warfarin patients	1.60%	0.80%	0.86%	2.27%
Relative risk (HR) in events using apixaban compared with warfarin (CI)	0.79 (CI: 0.66–0.95)	0.42 (CI: 0.30–0.58)	1.00** (CI:0.7–1.15)	0.79 (CI: 0.68–0.93)
Edoxaban (Giugliano et al, 2013)^Citation11
1-year event risk among warfarin patients	1.80%	0.85%	1.23%
Relative risk (HR) in events using edoxaban 60 mg compared with warfarin (CI)+	1.00** (NS: 0.87; CI: 0.73–1.04)	0.47 (CI: 0.34–0.63)	1.23 (CI: 1.02–1.50)

Notes:

* “Other bleedings” are reported in some of the clinical trials. These are severe bleedings together with intracranial bleedings and gastrointestinal bleedings and summed up in these clinical trials as “major bleedings” following treatment. Because “other bleedings” were not reported in all four trials, these bleeding types were omitted from the present analysis;

** all relative risks (HR) that were not found significant in the clinical trials (NS = not significant) were set to 1.0 in the cost analysis; ;

+ only the 60 mg dose is included for edoxaban as this is the only approved dosage according to their SmPC.

Abbreviations: NA, not applicable; NOAC, non-vitamin K oral anticoagulants; RCT, randomized clinical trial; SmPC, Summary of Product Characteristics; CI, confidence interval; HR, hazard ratio.

Figure 1 Different cost perspectives in oral anticoagulant therapy.

Abbreviation: INR, international normalized ratio.

Figure 2 Annual costs per NVAF patient receiving warfarin versus dabigatran 110 mg and 150 mg (US$).^**

Notes: ^*Including the costs of stroke and bleedings; ^**annual costs for the warfarin alternative are presented in the white boxes in the figure, whereas the annual costs in the dabigatran alternative are presented in the gray shaded boxes.
Abbreviation: NVAF, nonvalvular atrial fibrillation.

Figure 3 Annual costs per NVAF patient receiving warfarin versus rivaroxaban 20 mg (US$).^**

Notes: ^*Including the costs of stroke and bleedings; ^**Annual costs for the Warfarin alternative are presented in the white boxes in the figure, whereas the annual costs in the rivaroxaban alternative are presented in the gray shaded boxes.
Abbreviation: NVAF, nonvalvular atrial fibrillation.

Figure 4 Annual costs per NVAF patient receiving warfarin versus apixaban 5 mg (US$).^**

Notes: ^*Including the costs of stroke and bleedings; ^**annual costs for the warfarin alternative are presented in the white boxes in the figure, whereas the annual costs in the apixaban alternative are presented in the gray shaded boxes.
Abbreviation: NVAF, nonvalvular atrial fibrillation.

Figure 5 Annual costs per NVAF patient receiving warfarin versus edoxaban 60 mg (US$).^**

Notes: ^*Including the costs of stroke and bleedings; ^**annual costs for the warfarin alternative are presented in the white boxes in the figure, whereas the annual costs in the edoxaban alternative are presented in the gray shaded boxes.
Abbreviation: NVAF, nonvalvular atrial fibrillation.

Table 2 Annual average costs of INR monitoring of warfarin patients (US$)

INR monitoring at:	Share of type of monitoring^Citation13	Danish Health Authorities^Citation13 – adjusted to 2015 charges*	Langkilde et al^Citation14 – adjusted to 2015 charges*	Vestergaard et al (2015)^Citation15	Average annual costs of INR monitoring
The general practitioner	60%	US$ 492	US$ 728	US$ 750	US$ 657
Hospital, ambulatory visit**	39%	US$ 1,269
Self-monitoring at home	1%	US$ 654
Tele-medicine monitoring	0.4%	US$ 680
Distributed total costs of INR monitoring		US$ 799	US$ 941	US$ 954	US$ 898‡

Notes:

* Cost calculations in Danish Health Authorities (Sundhedsstyrelsen, 2012)¹³ and in Langkilde et al. (2012)¹⁴ have for the INR monitoring in the GP setting been adjusted to 2015 charges¹⁶ (2015 prices);

** 12 annual visits assumed (one visit per month);

‡ the societal annual costs of INR-monitoring are calculated to US$ 1,212. The extra costs come from the patients transporting direct expenses and time used visiting the clinic for INR-monitoring following calculations by the Danish Health Authorities.¹³

Abbreviation: INR, international normalized ratio.

Table 3 Total extra costs of first-incident stroke and first-incident bleeding events in AF patients – 3-year present values (US$)

Cost elements	Stroke^Citation18,Citation19	Intracranial bleeding^Citation19	Gastrointestinal bleeding^Citation19
Health care sector costs	20,507	20,234	16,235
Municipality social care costs	8,080	8,429	3,428
Lost production costs	2,338	2,288	355
Total societal costs	30,925	30,950	20,019

Abbreviation: AF, atrial fibrillation.

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