Atrial fibrillation cost-effectiveness of therapy: Difference between revisions
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==Overview== | ==Overview== | ||
[[Warfarin]] has been approved by the FDA since 1954 and is available in inexpensive [[generic]] forms that can cost as little as $4 a month. Warfarin can reduce [[stroke]] in AF patients by more than 50% and reduces absolute risk of stroke per year by 2%.<ref name="pmid17693178">{{cite journal| author=Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY et al.| title=Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. | journal=Lancet | year= 2007 | volume= 370 | issue= 9586 | pages= 493-503 | pmid=17693178 | doi=10.1016/S0140-6736(07)61233-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17693178 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18063732 Review in: Evid Based Med. 2007 Dec;12(6):172] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17975861 Review in: ACP J Club. 2007 Nov-Dec;147(3):59] </ref><ref name="pmid17577005">{{cite journal| author=Hart RG, Pearce LA, Aguilar MI| title=Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. | journal=Ann Intern Med | year= 2007 | volume= 146 | issue= 12 | pages= 857-67 | pmid=17577005 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17577005 }} </ref> Patients taking warfarin require frequent monitoring with blood tests and there are high medical costs associated with potential complications from over- or under-[[anticoagulation]]. | [[Warfarin]] has been approved by the FDA since 1954 and is available in inexpensive [[generic]] forms that can cost as little as $4 a month. Warfarin can reduce [[stroke]] in AF patients by more than 50% and reduces absolute risk of stroke per year by 2%.<ref name="pmid17693178">{{cite journal| author=Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY et al.| title=Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. | journal=Lancet | year= 2007 | volume= 370 | issue= 9586 | pages= 493-503 | pmid=17693178 | doi=10.1016/S0140-6736(07)61233-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17693178 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18063732 Review in: Evid Based Med. 2007 Dec;12(6):172] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17975861 Review in: ACP J Club. 2007 Nov-Dec;147(3):59] </ref><ref name="pmid17577005">{{cite journal| author=Hart RG, Pearce LA, Aguilar MI| title=Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. | journal=Ann Intern Med | year= 2007 | volume= 146 | issue= 12 | pages= 857-67 | pmid=17577005 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17577005 }} </ref> Patients taking warfarin require frequent monitoring with blood tests and there are high medical costs associated with potential complications from over- or under-[[anticoagulation]]. | ||
Alternative newer agents such as [[dabigatran]], [[apixaban]], [[rivaroxaban]], and [[edoxaban]] are also available for treatment and prevention of stroke and [[hemorrhage]] in AF patients. Unlike on warfarin, patients taking these NOACs do not require regular monitoring. NOACs are, however, more expensive than warfarin. The debate regarding the cost-effectiveness of NOACs is ongoing, as it depends on the drugs’ price, risk of bleeding, and quality-of-life for patients taking the medication. Multiple studies have demonstrated that overall NOACs are cost-effective medications compared to warfarin among patients with poor control of [[international normalized ratio]] ([[INR]]) with warfarin or with an increased risk of stroke or hemorrhage.<ref name="pmid23549134">{{cite journal| author=Harrington AR, Armstrong EP, Nolan PE, Malone DC| title=Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. | journal=Stroke | year= 2013 | volume= 44 | issue= 6 | pages= 1676-81 | pmid=23549134 | doi=10.1161/STROKEAHA.111.000402 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23549134 }} </ref><ref name="pmid23796283">{{cite journal| author=Coyle D, Coyle K, Cameron C, Lee K, Kelly S, Steiner S et al.| title=Cost-effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with atrial fibrillation. | journal=Value Health | year= 2013 | volume= 16 | issue= 4 | pages= 498-506 | pmid=23796283 | doi=10.1016/j.jval.2013.01.009 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23796283 }} </ref><ref name="pmid25512096">{{cite journal| author=Janzic A, Kos M| title=Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control. | journal=Pharmacoeconomics | year= 2015 | volume= 33 | issue= 4 | pages= 395-408 | pmid=25512096 | doi=10.1007/s40273-014-0246-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25512096 }} </ref> | Alternative newer agents such as [[dabigatran]], [[apixaban]], [[rivaroxaban]], and [[edoxaban]] are also available for treatment and prevention of stroke and [[hemorrhage]] in AF patients. Unlike on warfarin, patients taking these NOACs do not require regular monitoring. NOACs are, however, more expensive than warfarin. The debate regarding the cost-effectiveness of NOACs is ongoing, as it depends on the drugs’ price, risk of bleeding, and quality-of-life for patients taking the medication. Multiple studies have demonstrated that overall NOACs are cost-effective medications compared to warfarin among patients with poor control of [[international normalized ratio]] ([[INR]]) with warfarin or with an increased risk of stroke or hemorrhage.<ref name="pmid23549134">{{cite journal| author=Harrington AR, Armstrong EP, Nolan PE, Malone DC| title=Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. | journal=Stroke | year= 2013 | volume= 44 | issue= 6 | pages= 1676-81 | pmid=23549134 | doi=10.1161/STROKEAHA.111.000402 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23549134 }} </ref><ref name="pmid23796283">{{cite journal| author=Coyle D, Coyle K, Cameron C, Lee K, Kelly S, Steiner S et al.| title=Cost-effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with atrial fibrillation. | journal=Value Health | year= 2013 | volume= 16 | issue= 4 | pages= 498-506 | pmid=23796283 | doi=10.1016/j.jval.2013.01.009 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23796283 }} </ref><ref name="pmid25512096">{{cite journal| author=Janzic A, Kos M| title=Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control. | journal=Pharmacoeconomics | year= 2015 | volume= 33 | issue= 4 | pages= 395-408 | pmid=25512096 | doi=10.1007/s40273-014-0246-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25512096 }} </ref> | ||
==Cost-Effectiveness of Therapy== | |||
===Warfarin=== | ===Warfarin=== | ||
[[Warfarin]] is an inexpensive anticoagulant that has been demonstrated to have efficacy in lowering risk of stroke in individuals with AF. One study found that warfarin had a $12,000 cost per quality adjusted life year (QALY) when compared to [[aspirin]], well below the typical $50,000 threshold for cost-effectiveness.<ref name="pmid21606397">{{cite journal| author=Shah SV, Gage BF| title=Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. | journal=Circulation | year= 2011 | volume= 123 | issue= 22 | pages= 2562-70 | pmid=21606397 | doi=10.1161/CIRCULATIONAHA.110.985655 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21606397 }} </ref> Despite its benefits, patients taking warfarin report a higher risk of fatal bleeding than on other newer NOAC agents.<ref name="pmid19717844">{{cite journal| author=Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A et al.| title=Dabigatran versus warfarin in patients with atrial fibrillation. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 12 | pages= 1139-51 | pmid=19717844 | doi=10.1056/NEJMoa0905561 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19717844 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20083817 Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-2] </ref> However, there is ultimately a consensus that warfarin is a cost-effective treatment compared to no therapy and aspirin in both moderate- and high-risk patients with AF. Due to the very low cost of warfarin, the cost-effectiveness of newer agents is always compared to that of warfarin. | [[Warfarin]] is an inexpensive anticoagulant that has been demonstrated to have efficacy in lowering risk of stroke in individuals with AF. One study found that warfarin had a $12,000 cost per quality adjusted life year (QALY) when compared to [[aspirin]], well below the typical $50,000 threshold for cost-effectiveness.<ref name="pmid21606397">{{cite journal| author=Shah SV, Gage BF| title=Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. | journal=Circulation | year= 2011 | volume= 123 | issue= 22 | pages= 2562-70 | pmid=21606397 | doi=10.1161/CIRCULATIONAHA.110.985655 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21606397 }} </ref> Despite its benefits, patients taking warfarin report a higher risk of fatal bleeding than on other newer NOAC agents.<ref name="pmid19717844">{{cite journal| author=Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A et al.| title=Dabigatran versus warfarin in patients with atrial fibrillation. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 12 | pages= 1139-51 | pmid=19717844 | doi=10.1056/NEJMoa0905561 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19717844 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20083817 Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-2] </ref> However, there is ultimately a consensus that warfarin is a cost-effective treatment compared to no therapy and aspirin in both moderate- and high-risk patients with AF. Due to the very low cost of warfarin, the cost-effectiveness of newer agents is always compared to that of warfarin. | ||
Latest revision as of 19:55, 13 August 2015
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rebecca Cohen
Overview
Warfarin has been approved by the FDA since 1954 and is available in inexpensive generic forms that can cost as little as $4 a month. Warfarin can reduce stroke in AF patients by more than 50% and reduces absolute risk of stroke per year by 2%.[1][2] Patients taking warfarin require frequent monitoring with blood tests and there are high medical costs associated with potential complications from over- or under-anticoagulation.
Alternative newer agents such as dabigatran, apixaban, rivaroxaban, and edoxaban are also available for treatment and prevention of stroke and hemorrhage in AF patients. Unlike on warfarin, patients taking these NOACs do not require regular monitoring. NOACs are, however, more expensive than warfarin. The debate regarding the cost-effectiveness of NOACs is ongoing, as it depends on the drugs’ price, risk of bleeding, and quality-of-life for patients taking the medication. Multiple studies have demonstrated that overall NOACs are cost-effective medications compared to warfarin among patients with poor control of international normalized ratio (INR) with warfarin or with an increased risk of stroke or hemorrhage.[3][4][5]
Cost-Effectiveness of Therapy
Warfarin
Warfarin is an inexpensive anticoagulant that has been demonstrated to have efficacy in lowering risk of stroke in individuals with AF. One study found that warfarin had a $12,000 cost per quality adjusted life year (QALY) when compared to aspirin, well below the typical $50,000 threshold for cost-effectiveness.[6] Despite its benefits, patients taking warfarin report a higher risk of fatal bleeding than on other newer NOAC agents.[7] However, there is ultimately a consensus that warfarin is a cost-effective treatment compared to no therapy and aspirin in both moderate- and high-risk patients with AF. Due to the very low cost of warfarin, the cost-effectiveness of newer agents is always compared to that of warfarin.
Dabigatran
One NOAC that has been studied extensively for cost-effectiveness is dabigatran (Padraxa). Dabigatran is an oral anticoagulant approved for stroke prophylaxis in Europe at either a high-dose (150 mg) or a low-dose (110 mg) and approved by the FDA only at the 150 mg dosage. Dabigatran costs approximately $9 a day, though this higher cost compared to warfarin is somewhat offset by the lack of required regular blood tests.
Studies have demonstrated that high-dose dabigatran is more cost-effective than the lower dosage. Compared to warfarin, high-dose dabigatran costs between $6,944 and $45,372 per QALY.[8][3][4][9][6][10][5] The cost per QALY of low-dose dabigatran compared to warfarin ranges from $23,016 per QALY [10] to $86,000 per QALY[6], though most estimates fall in the range of $51,000 to $66,000 per QALY [8][4][9], which are above the $50,000 threshold for cost-effectiveness. It should be noted that the study with the highest estimations of the marginal cost per QALY for both high- and low-dose dabigatran has a higher average patient age than other dabigatran cost-effectiveness studies. Dabigatran 150 mg is superior to dabigatran 110 mg, as it had a lower increase in QALYs at a higher incremental cost. For this reason, high-dose dabigatran is the preferred therapy in terms of cost-effectiveness and low-dose dabigatran is not cost-effective for patients with AF at risk of stroke or hemorrhage.[4][9][10] Estimates of cost-effectiveness are sensitive to the time horizon (shorter time horizon increased cost) and the effectiveness of warfarin in controlling INR risk of hemorrhage (higher cost per QALY when INR is well controlled by warfarin).
Apixaban
Apixaban (Eliquis) is another option for stroke prophylaxis in AF patients. A number of studies have demonstrated apixaban is a cost-effective treatment option with a cost ranging from $15,026 to $24,312 per QALY gained compared to warfarin.[3][4][5] One study found that apixaban is the most cost-effective NOAC with the highest number of QALYs gained at the lowest incremental cost[5], while another found that the patients taking 150 mg dabigatran gained the same number of QALYs, but at a slightly higher cost meaning apixaban is superior to dabigatran treatment in terms of cost-effectiveness.[4] This differential in cost-effectiveness, however, could be offset by a 10% reduction in the price of apixaban to below $3.01 per tablet.[4]
Rivaroxaban
When compared to warfarin for prophylaxis, studies have demonstrated that rivaroxaban (Xarelto) has a cost per QALY that ranges from $3,190 to $73,443 (€66,328) per QALY.[3][4][5] Two of the three studies found that rivaroxaban is a cost-effective treatment, with a cost per QALY considerably lower than the $50,000 willingness-to-pay threshold for cost-effectiveness.[3][4] Rivaroxaban may be a cost-effective treatment for patients, as it is sometimes superior to other cost-effective NOACs, such as 150 mg dabigatran and apixaban, but if the cost of the medication were lowered to be no more than $1.10 per tablet, the drug would be the preferred, more cost-effective stroke prophylaxis medication.[4]
Edoxaban
Edoxaban (Savaysa or Lixiana) is another direct factor Xa inhibitor approved by the FDA. It is a cost-effective form of prophylaxis and has been demonstrated to cost $8,511 (€7,713) [11] and $21,031 (€18,994) [5] per QALY, well below the typical $50,000 willingness-to-pay threshold. Another study found that edoxaban could be cost-effective compared to warfarin depending on the time horizon of the medication. At nine years the cost per QALY of edoxaban is $50,392 and this ratio becomes favorable as the timeline increases.[12] Another factor that influences the cost-effectiveness of the medication is the patients’ risk of bleeding and heart complications; for patients with an additional risk factor for stroke and intracranial hemorrhage, edoxaban is cost-effective.
References
- ↑ Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY; et al. (2007). "Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial". Lancet. 370 (9586): 493–503. doi:10.1016/S0140-6736(07)61233-1. PMID 17693178. Review in: Evid Based Med. 2007 Dec;12(6):172 Review in: ACP J Club. 2007 Nov-Dec;147(3):59
- ↑ Hart RG, Pearce LA, Aguilar MI (2007). "Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation". Ann Intern Med. 146 (12): 857–67. PMID 17577005.
- ↑ 3.0 3.1 3.2 3.3 3.4 Harrington AR, Armstrong EP, Nolan PE, Malone DC (2013). "Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation". Stroke. 44 (6): 1676–81. doi:10.1161/STROKEAHA.111.000402. PMID 23549134.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 Coyle D, Coyle K, Cameron C, Lee K, Kelly S, Steiner S; et al. (2013). "Cost-effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with atrial fibrillation". Value Health. 16 (4): 498–506. doi:10.1016/j.jval.2013.01.009. PMID 23796283.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Janzic A, Kos M (2015). "Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control". Pharmacoeconomics. 33 (4): 395–408. doi:10.1007/s40273-014-0246-7. PMID 25512096.
- ↑ 6.0 6.1 6.2 Shah SV, Gage BF (2011). "Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation". Circulation. 123 (22): 2562–70. doi:10.1161/CIRCULATIONAHA.110.985655. PMID 21606397.
- ↑ Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A; et al. (2009). "Dabigatran versus warfarin in patients with atrial fibrillation". N Engl J Med. 361 (12): 1139–51. doi:10.1056/NEJMoa0905561. PMID 19717844. Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-2
- ↑ 8.0 8.1 Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS; et al. (2011). "Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation". Ann Intern Med. 154 (1): 1–11. doi:10.7326/0003-4819-154-1-201101040-00289. PMID 21041570. Review in: Ann Intern Med. 2011 Jun 21;154(12):JC6-12
- ↑ 9.0 9.1 9.2 Pink J, Lane S, Pirmohamed M, Hughes DA (2011). "Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses". BMJ. 343: d6333. doi:10.1136/bmj.d6333. PMC 3204867. PMID 22042753.
- ↑ 10.0 10.1 10.2 Sorensen SV, Kansal AR, Connolly S, Peng S, Linnehan J, Bradley-Kennedy C; et al. (2011). "Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: a Canadian payer perspective". Thromb Haemost. 105 (5): 908–19. doi:10.1160/TH11-02-0089. PMID 21431243.
- ↑ Rognoni C, Marchetti M, Quaglini S, Liberato NL (2015). "Edoxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis". J Thromb Thrombolysis. 39 (2): 149–54. doi:10.1007/s11239-014-1104-3. PMID 24973057.
- ↑ Lee S, Mullin R, Blazawski J, Coleman CI (2012). "Cost-effectiveness of apixaban compared with warfarin for stroke prevention in atrial fibrillation". PLoS One. 7 (10): e47473. doi:10.1371/journal.pone.0047473. PMC 3467203. PMID 23056642.