The Use of Atrial Fibrillation Risk Stratification Scores ...

The Use of Atrial Fibrillation Risk Stratification Scores as Reimbursement Criteria for Direct Oral Anticoagulants: Perspectives from International Drug Plans

Service Line: Environmental ScanningIssue: 66Version: 1.0Publication Date: November 2017Report Length: 22 Pages

ENVIRONMENTAL SCAN

ENVIRONMENTAL SCAN The Use of Atrial Fibrillation Risk Stratification Scores as Reimbursement Criteria for Direct Oral Anticoagulants: Perspectives from International Drug Plans 2

Authors: Ndegwa, Sarah; Boucher, Michel; Farrah, Kelly

Cite As: The Use of Atrial Fibrillation Risk Stratification Scores as Reimbursement Criteria for Direct Oral Anticoagulants: Perspectives from International Drug Plans. Ottawa:

CADTH; 2017. (Environmental scan; no. 66).

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Summary• Atrial fibrillation is the most common cardiac arrhythmia. It increases the risk of stroke

five-fold, resulting in significant morbidity and mortality. Various risk stratification scores have been developed to determine the risk of stroke in patients with atrial fibrillation. Therapy with oral anticoagulants has shown to be effective for reducing the risk of stroke and systemic embolism in this population.

• This Environmental Scan aims to determine whether certain risk stratification scores (including CHADS2, CHAD65, or CHA2DS2-VASc) are used by international drug programs as reimbursement criteria for direct oral anticoagulants (DOACs) (apixaban, dabigatran, edoxaban, and rivaroxaban) for the management of patients with atrial fibrillation.

• Information was retrieved from publicly funded drug plans in the US, Europe as well as Australia and New-Zealand. In order to complement this information, the websites of the 10 largest private health insurers in the US were also searched.

• Most publicly funded drug plans reimburse DOACs based on specific clinical criteria, many of which are risk factors used in calculating the CHADS2 score. Risk stratification scores are not commonly used as part of the reimbursement criteria for DOACs by international publicly funded drug plans or private plans in the US. In cases where the CHADS2 or CHA2DS2-VASc scores are part of criteria, it does not appear that one score is used more than the other. CHAD65 was not identified in any of the adjudication information for the reimbursement of DOACs.

• In summary, no specific risk stratification score is consistently used by international drug plans to adjudicate DOACs for patients with atrial fibrillation.

ContextAtrial fibrillation is the most common cardiac arrhythmia affecting approximately 350,000 Canadians.1-3 Atrial fibrillation increases the risk of stroke five-fold, resulting in significant morbidity and mortality.2,4 A Canadian study reported that on the basis of data from fiscal year 2007 to 2008, the estimated total inpatient costs due to atrial fibrillation was $815 million.2 The prevalence of atrial fibrillation is expected to increase as Canada’s population ages, which will impose a significant burden on the health care system.

Therapy with oral anticoagulants has shown to be effective for reducing the risk of stroke and systemic embolism in patients with atrial fibrillation.1 However, anticoagulants increase the risk of bleeding; hence treatment decisions should consider a balance between the risk of thromboembolic events and bleeding. Historically, warfarin was the mainstay of stroke prophylaxis. More recently, direct oral anticoagulants (DOACs) such as dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Lixiana) have been introduced to clinical practice. These DOACs were all reviewed by the CADTH Common Drug Review for the following indication: prevention of stroke and systemic embolism in patients with atrial fibrillation. Listing recommendations were also developed for this indication by the CADTH Canadian Drug Expert Committee to inform reimbursement policies by publicly funded drug programs in Canada.5-10 These recommendations were based on both clinical and economic data. Of note, since their approval in Canada, the number of prescriptions for DOACs for use in patients with atrial fibrillation has been steadily increasing.11,12


Various risk stratification scores have been developed to determine the risk of stroke in patients with atrial fibrillation.13,14 Two commonly used scoring systems are the CHADS2 score (Table 1) and the more recently introduced CHA2DS2-VASc score that includes three additional risk factors (Table 2). A third one, CHAD65, is an algorithm with initial risk stratification by age (≥ 65 years and < 65 years) and further stratification of individuals < 65 years of age, based on the CHADS2 score.15 A recent CADTH literature review found that the CHA2DS2-VASc score better discriminated stroke risk in patients with very low risk of stroke or thromboembolism when compared with the CHADS2 score.13 No relevant studies on the CHAD65 algorithm were identified in the review.13

Table 1: Details of CHADS2 Score14

Item Score

Congestive heart failure 1

Hypertension 1

Age ≥ 75 years 1

Diabetes mellitus 1

History of stroke or transient ischemic attack 2

Maximum Score 6

Table 2: Details of CHA2DS2-VASc Score14

Item Score

Congestive heart failure 1

Hypertension 1

Age ≥ 75 years 2

Diabetes mellitus 1

History of stroke, transient ischemic attack, or thromboembolic event 2

Vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque)

1

Age 65 to 74 years 1

Sex category (female) 1

Maximum Score 9


At the time CDEC released its recommendations on DOACs for use in patients with atrial fibrillation,5-10 CHADS2 was the most accepted scoring system. It was also the risk score used in randomized clinical trials evaluating DOACs in patients with atrial fibrillation.16-19 However, guidelines have evolved over the years and other scoring systems have started to be used. Currently, the CHA2DS2-VASc score is commonly advocated in most guidelines including those issued by the National Institute for Health and Care Excellence, American College of Cardiology/American Heart Association, and the European Society of Cardiology.20-22 The Canadian Cardiovascular Society recommends the use of the CHAD65 score to guide treatment.15 This Environmental Scan of Health Technology Assessment (HTA) reimbursement recommendations and international drug plan reimbursement criteria will inform policy development activities for DOACs in Canada.

ObjectivesThe objective of this Environmental Scan is to retrieve and report on drug program criteria and HTA recommendations used internationally for the reimbursement of DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) for the management of patients with atrial fibrillation. More specifically, this Environmental Scan aims to determine whether certain risk stratification scores (including CHADS2, CHAD65, or CHA2DS2-VASc) are used as reimbursement criteria for DOACs. Given the targeted audience, this report is particularly interested in information from publicly funded drug plans. The following questions are addressed:

• Which DOACs are currently listed on international publicly funded drug plans for the management of patients with atrial fibrillation?

• What are the eligibility criteria for the reimbursement of DOACs by international publicly funded drug plans for patients with atrial fibrillation?

• Are risk stratification scores (including CHADS2, CHA2DS2-VASc, or CHAD 65) included in these eligibility criteria?

• Do private drug plans in the US include risk stratification scores in reimbursement criteria?

MethodsThe findings of this Environmental Scan are based on searching for reimbursement criteria and related information online. Below is a description of the literature search strategy used.

Literature SearchA formal grey literature search was conducted from April 2017 to June 2017. The search was not limited by language or publication year. The websites of selected HTA agencies and publicly funded drug plans from North America (US), Europe, Oceania (Australia and New Zealand) were searched for HTA reimbursement recommendations and reimbursement criteria for DOACs used for the prevention of stroke and systemic embolism in patients with atrial fibrillation. The International Society for Pharmacoeconomics and Outcomes Research road maps23,24 were used to identify the authorities responsible for providing HTA reimbursement recommendations and reimbursement criteria decisions in each country. For publicly funded drug plans located in the US, Medicaid programs from various states (including larger, densely populated states and smaller, rural states) were selected as well as Medicare Part D and Veterans Affairs.


Below is the list of international HTA agencies and publicly funded drug plans that were searched:

• US: Agency for Healthcare Research and Quality, Medicare Part D, Medicaid (New York, California, Texas, Oregon, Washington, Iowa), Veterans Affairs

• UK: National Institute for Health and Care Excellence, National Health Service UK Department of Health

• Scotland: Scottish Medicines Consortium, National Health Service Scotland Boards (regional)

• Germany: Federal Joint Committee, statutory health insurances

• France: National Health Authority, Ministry of Social Affairs and Health

• Belgium: National Institute for Health and Disability Insurance, Minister for Social Affairs and Public Health

• Italy: Italian Medicines Agency, National Health Service

• Poland: Agency for Health Technology Assessment, Ministry of Health

• Netherlands: National Health Care Institute; Ministry of Health, Welfare and Sport

• Sweden: Dental and Pharmaceutical Benefits Agency, pharmaceutical benefits scheme

• Spain: Spanish Agency for Health Technology Assessment; Ministry of Health, Social Services and Equality

• Norway: Norwegian Medicines Agency

• Australia: Pharmaceutical Benefits Advisory Committee, Pharmaceutical Benefits Scheme

• New Zealand: Pharmaceutical Management Agency, Pharmaceutical Schedule.

In order to complement information from publicly funded organizations, the websites of the 10 largest private health insurers in the US (according to a recent study25) were also searched:

• UnitedHealth Group

• Kaiser Foundation Group

• Anthem Inc. (formerly WellPoint Inc. Group)

• Aetna Group

• Humana Group

• HCSC Group

• Cigna Health Group

• Highmark Group

• Blue Shield of California Group

• Independence Blue Cross Group.

Information Retrieval and SelectionA review of information from the grey literature search was conducted to identify relevant information for the Environmental Scan. This report focuses on information relevant for the reimbursement of DOACs in the management of atrial fibrillation. All identified eligibility criteria for the reimbursement of DOACs are listed with risk stratification scores (when used as part of the criteria) highlighted in bold. Information from Medicaid and private US plans


were only included if they used risk stratification scores as part of the reimbursement criteria. Guidelines for the management of atrial fibrillation and prescribing practices for DOACs were considered outside the scope of the report and excluded. Google Translate was used to translate information on websites and documents in other languages into English.

FindingsThe data source for this Environmental Scan is the information that was retrieved from the literature search. Due to the complexity of the different programs and tier levels that make up Medicare Part D, it was not possible to capture meaningful reimbursement data. Findings are summarized in Table 3.

DOACs Reimbursed on Publicly Funded Drug Plans for Atrial Fibrillation

Of the selected publicly funded drug plans, many reimbursed all four DOACs with the exception of Germany (apixaban and edoxaban listed), France (apixaban, dabigatran, and rivaroxaban listed), Poland (no DOACs listed for atrial fibrillation), Australia (apixaban, dabigatran, and rivaroxaban listed), and New Zealand (dabigatran listed). The publicly funded drug plans in the US selected for this Environmental Scan required additional criteria for some DOACs (non-preferred) to be reimbursed.

Eligibility Criteria for DOAC Reimbursement

Most of the selected publicly funded drug plans reimbursed DOACs based on specific clinical criteria with the exception of New Zealand, which listed dabigatran without any Special Authority restriction. Most of these criteria were risk factors used in calculating the CHADS2 score. Risk stratification scores were used as part of the reimbursement criteria for DOACs by Medicaid Iowa (CHA2DS2-VASc), Veterans Affairs (either CHADS2 or CHA2DS2-VASc), and the Italian National Health Service (Servizio Sanitario Nazionale) (CHA2DS2-VASc). Risk stratification scores were also included in HTA reimbursement recommendations from the UK National Institute for Health and Care Excellence (CHA2DS2-VASc) and New Zealand Pharmaceutical Management Agency (CHADS2).

US Private Health Plan Use of Risk Stratification Scores

Of the top 10 US private health plans selected for inclusion in this Environmental Scan, only Kaiser Foundation Group included the use of a risk stratification score (either CHADS2 or CHA2DS2-VASc) as part of the reimbursement criteria for the use of DOACs in patients with atrial fibrillation.


Table 3: Adjudication Information for Reimbursement of DOACsCountry International HTA Reimbursement Recommendations and Criteriaa

North America

US HTA Reimbursement Recommendations

Agency for Healthcare Research and QualityNo recommendations could be identified.

Reimbursement Criteria

Publicly Funded Drug Plans

Medicaid Iowa (State Level)26

Apixaban, Dabigatran, Edoxaban, RivaroxabanAll four DOACs reimbursed.

Edoxaban is a non-preferred drug that requires prior authorization with the following criteria:• patient does not have a mechanical heart valve• patient does not have active bleeding• patient has the presence of at least one additional risk factor for stroke, with a

CHA2DS2-VASc score ≥ 1• recent creatinine clearance is provided• Child–Pugh score is provided• current body weight is provided• patient has documentation of a trial and therapy failure at a therapeutic dose with at least

two preferred DOACs (when not medically contraindicated)• patient has had 5 to 10 days of initial therapy with a parenteral anticoagulant (low molecular

weight heparin or unfractionated heparin).

Veterans Affairs27

Apixaban, Dabigatran, Edoxaban, RivaroxabanAll reimbursed for non-valvular atrial fibrillation with the presence of at least one additional risk factor for stroke based on CHADS2 or CHA2DS2-VASc score ≥ 1.

ApixabanOne of the following additional criteria must be selected for patient to be eligible:• renal impairment (CrCl 25 mL/minute to 50 mL/minute)• considered at increased risk of bleeding (including GI bleeding or age ≥ 75 years,

hypertension, prior stroke, and anemia)• patient is intolerant to or is not a candidate for dabigatran.


Country International HTA Reimbursement Recommendations and Criteriaa

North America

US EdoxabanOne of the following additional criteria must be selected for patient to be eligible:• renal impairment (CrCl 30 mL/minute to 50 mL/minute)• medical or other compelling reason to avoid twice-daily medication• need for use of a pill reminder box• considered at increased risk of bleeding (including age ≥ 75 years, hypertension, prior stroke,

and anemia)• patient is intolerant to or is not a candidate for dabigatran.

RivaroxabanOne of the following additional criteria must be selected for patient to be eligible:• renal impairment (CrCl 30 mL/minute to 50 mL/minute)• medical or other compelling reason to avoid twice-daily medication• unable to swallow whole pills• need for use of a pill reminder box• patient is intolerant to or is not a candidate for dabigatran.

Private Drug Plans

Kaiser Foundation Group (Private Drug Plan)28-31

DabigatranListed on formulary as a preferred drug for the prevention of thrombosis in patients with non valvular atrial fibrillation.

Apixaban, Edoxaban, RivaroxabanNon-formulary DOACs reimbursed for the prevention of thrombosis in patients with non valvular atrial fibrillation when the following criteria are met:• documented diagnosis of atrial fibrillation• CHA2DS2-VASc score ≥ 2 or CHADS2 score ≥ 1• intolerance or contraindication to dabigatran or have a condition where dabigatran is not

preferred (e.g., history of GI bleed)• estimated CrCl of < 95 mL/minute (criteria for edoxaban only)• at least one of the following:

• undergoing cardioversion (criteria for rivaroxaban and apixaban only)• intolerance or contraindication to warfarin• history of intracranial hemorrhage on warfarin• challenges in getting timely blood draws• failed to maintain therapeutic INR or time to therapeutic range < 50% despite history of

good adherence to warfarin dosage.

Note: Order of preference is dabigatran (preferred drug) followed by rivaroxaban, then apixaban, and edoxaban.



Europe

UK HTA Reimbursement Recommendations

National Institute for Health and Care Excellence20

General• Consider anticoagulation for men with CHA2DS2-VASc score of 1, taking bleeding risk into account.• Offer anticoagulation to people with a CHA2DS2-VASc score ≥ 2, taking bleeding risk into account.• Do not offer stroke prevention therapy to people aged under 65 years with atrial fibrillation

and no risk factors other than their gender (that is, very low risk of stroke equating to a CHA2DS2-VASc score of 0 for men or 1 for women).

ApixabanRecommended for prevention of stroke and systemic embolism in people with non-valvular atrial fibrillation with one or more risk factors including:• prior stroke or transient ischemic attack• age ≥ 75 years• hypertension• diabetes mellitus• symptomatic heart failure.

DabigatranRecommended for prevention of stroke and systemic embolism in people with non-valvular atrial fibrillation with one or more risk factors including:• previous stroke, transient ischemic attack, or systemic embolism• left ventricular ejection fraction < 40%• symptomatic heart failure (New York Heart Association class ≥ 2)• age ≥ 75 years• age ≥ 65 years with one of the following:

• diabetes mellitus• coronary artery disease• hypertension.

RivaroxabanRecommended for prevention of stroke and systemic embolism in people with non-valvular atrial fibrillation with one or more risk factors including:• congestive heart failure• hypertension• age ≥ 75 years• diabetes mellitus• prior stroke or transient ischemic attack.


National Health Service UK Department of HealthNo reimbursement criteria could be identified.



Europe

Scotland HTA Reimbursement Recommendations

Scottish Medicines Consortium32-35

ApixabanApixaban is accepted for use within NHS Scotland for prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors including:• prior stroke or transient ischemic attack• age ≥ 75 years• hypertension• diabetes mellitus• symptomatic heart failure (New York Heart Association class ≥ 2).

DabigatranDabigatran is accepted for use within NHS Scotland for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more of the following risk factors:• previous stroke, transient ischemic attack, or systemic embolism• left ventricular ejection fraction < 40%• symptomatic heart failure (New York Heart Association class ≥ 2)• age ≥ 75 years• age ≥ 65 years with one of the following:


EdoxabanEdoxaban is accepted for use within NHS Scotland for prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors including:• congestive heart failure• hypertension• age ≥ 75 years• diabetes mellitus• prior stroke or transient ischemic attack.



Europe

Scotland RivaroxabanRivaroxaban is accepted for restricted use within NHS Scotland for prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors including:• congestive heart failure• hypertension• age ≥ 75 years• diabetes mellitus• prior stroke or transient ischemic attack.

SMC restriction: Rivaroxaban is accepted for use in patients who have poor INR control despite evidence that they are complying with a coumarin anticoagulant and in patients who are allergic to or unable to tolerate coumarin anticoagulants.


National Health Service (NHS) Scotland Boards (Regional)No reimbursement criteria could be identified.

Germany HTA Reimbursement Recommendations

Federal Joint Committee36,37

Apixaban and EdoxabanFor the prophylaxis of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation and one or more risk factors including:• congestive heart failure• hypertension• age ≥ 75 years• diabetes mellitus• history of stroke or transient ischemic attack.


Statutory Health Insurances38,39

Apixaban and EdoxabanFor prophylaxis of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation and one or more risk factors including:• history of stroke or transient ischemic attack• age ≥ 75 years• hypertension• diabetes mellitus• symptomatic heart failure (New York Heart Association class ≥ 2).



Europe

France HTA Reimbursement Recommendations

National Health Authority40-43

Apixaban and DabigatranRecommended on the list of medicines refundable by National Health Insurance (NHI) for prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more of the following risk factors:• previous stroke, transient ischemic attack, or systemic embolism• left ventricular ejection fraction < 40%• symptomatic heart failure (New York Heart Association class ≥ 2)• age ≥ 75 years• age ≥ 65 years with one of the following conditions


EdoxabanThe committee found no clinical benefit in comparison to other oral anticoagulants in the prevention of stroke and systemic embolism associated with non-valvular atrial fibrillation in patients with one or more risk factor(s). Accordingly, edoxaban is not on the list of medicines refundable by NHI.

RivaroxabanRecommended on the list of medicines refundable by NHI for prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more of the following risk factors:• congestive heart failure• hypertension• age ≥ 75 years• diabetes• history of stroke or transient ischemic attack.


Ministry of Social Affairs and Health44

Apixaban, Dabigatran, RivaroxabanReimbursed by NHI for the prevention of stroke and systemic embolism in atrial non-valvular fibrillation in adults with certain risk factors but other criteria not specified.



Europe

Belgium HTA Reimbursement Recommendations

National Institute for Health and Disability InsuranceNo recommendations could be identified.


Minister for Social Affairs and Public Health45

Apixaban, Dabigatran, Edoxaban, RivaroxabanReimbursed for non-valvular atrial fibrillation associated with one or more of the following other risk factors:• history of stroke, transient ischemic attack, or systemic embolism• left ventricular ejection fraction < 40%• symptomatic heart failure (New York Heart Association class ≥ 2)• age ≥ 75 years• age ≥ 65 years associated with any of the following conditions:

• diabetes• coronary artery disease• high blood pressure.

Italy HTA Reimbursement Recommendations

Italian Medicines AgencyNo recommendations could be identified.


National Health Service46-50

Apixaban, Dabigatran, Edoxaban, RivaroxabanReimbursed for the prevention of systemic stroke and embolism in adult patients with non-valvular atrial fibrillation with:• CHA2DS2-VASc score ≥ 1 and HAS-BLED score > 3 (score estimating bleeding risk)• INR unstable in the last six months with time in therapeutic range < 70%.

Poland HTA Reimbursement Recommendations

Agency for Health Technology Assessment51

The council considered it unreasonable to qualify dabigatran as a listed benefit for the prevention of systemic stroke and embolism in adult patients with atrial fibrillation due to possible serious adverse effects including increased risk of major bleeding and death.


Ministry of Health52

No DOACs are reimbursed for atrial fibrillation.



Europe

Netherlands HTA Reimbursement Recommendations

National Health Care InstituteNo recommendations could be identified.


Ministry of Health, Welfare and Sport53

Apixaban, Dabigatran, Edoxaban, RivaroxabanListed in the drug reimbursement system for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors including:• congestive heart failure• hypertension• age ≥ 75 years• diabetes mellitus• previous stroke or transient ischemic attack.

Sweden HTA Reimbursement Recommendations

Dental and Pharmaceutical Benefits AgencyNo recommendations could be identified.


Pharmaceutical Benefits Scheme54-57

Apixaban, Dabigatran, Edoxaban, RivaroxabanPrevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors including:• previous stroke or transient ischemic attack• age ≥ 75 years• heart failure (New York Heart Association class ≥ 2)• diabetes mellitus• hypertension.

Spain HTA Reimbursement Recommendations

Spanish Agency for Health Technology AssessmentNo recommendations could be identified.


Ministry of Health, Social Services and Equality58

Apixaban, Dabigatran, Edoxaban, RivaroxabanAll listed as funded pharmaceuticals but reimbursement criteria not specified.



Europe

Norway HTA Reimbursement Recommendations

Norwegian Medicines AgencyNo recommendations could be identified.


Norwegian Medicines Agency59-63

Apixaban, Dabigatran, Edoxaban, RivaroxabanPrevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors including:• previous stroke or transient ischemic attack• age ≥ 75 years• hypertension• diabetes mellitus• symptomatic heart failure (New York Heart Association class ≥ 2).

Oceania

Australia HTA Reimbursement Recommendations

Pharmaceutical Benefits Advisory Committee64-66

Apixaban, Dabigatran, RivaroxabanReimbursement via the pharmaceutical benefits scheme is recommended for patients with non-valvular atrial fibrillation with one or more risk factors for developing stroke or systemic embolism including:• previous stroke (ischemic attack or unknown type)• transient ischemic attack or non-central nervous system systemic embolism• age ≥ 75 years• hypertension• diabetes mellitus• heart failure and/or left ventricular ejection fraction ≤ 35%.


Pharmaceutical Benefits Scheme67

Apixaban, Dabigatran, Rivaroxaban,Patient must have non-valvular atrial fibrillation with one or more risk factors for developing stroke or systemic embolism including:• previous stroke (ischemic attack or unknown type)• transient ischemic attack or non-central nervous system systemic embolism• age ≥ 75 years• hypertension• diabetes mellitus• heart failure and/or left ventricular ejection fraction ≤ 35%.



Oceania

New Zealand HTA Reimbursement Recommendations

Pharmaceutical Management Agency68-70

DabigatranThe committee recommended that dabigatran be funded with low priority (priority level is based on the assessment of several factors including clinical benefit over existing treatments and the economic impact on the government’s overall budget) for prevention of stroke, systemic embolism and reduction of vascular mortality in atrial fibrillation. The committee noted the supplier’s recommendation to limit dabigatran to patients who have a CHADS2 score ≥ 2 and who were contraindicated to warfarin or had trialled warfarin but INR levels failed to be maintained within the therapeutic range. The committee considered that it would be difficult to restrict dabigatran to certain subgroups of patients with atrial fibrillation without a significant risk of other patients with atrial fibrillation gaining access.

Apixaban, RivaroxabanThe committee recommended that rivaroxaban be listed on the Pharmaceutical Schedule for stroke prevention in non-valvular atrial fibrillation only if cost-neutral to dabigatran. The committee recommended that apixaban be listed for the treatment of stroke prevention in non-valvular atrial fibrillation only if cost-neutral to rivaroxaban and dabigatran. It was considered that there was no clinical need to reimburse rivaroxaban or apixaban with a Special Authority restriction, given dabigatran is listed without such restriction.


Pharmaceutical Schedule71,72

DabigatranListed without Special Authority restriction.

CrCl = creatinine clearance; DOAC = direct-acting oral anticoagulant; GI = gastrointestinal; HTA = health technology assessment; INR = international normalized ratio; NHS = National Health Service; SMC = Scottish Medicines Consortium.a In this table, non-valvular atrial fibrillation generally refers to atrial fibrillation in the absence of mitral stenosis, an artificial heart valve, or mitral valve repair.


LimitationsThe findings of this Environmental Scan present an overview of criteria used by selected international drug plans for the reimbursement of DOACs for the prevention of stroke and systemic embolism in patients with atrial fibrillation; they do not represent a comprehensive review of the topic. These findings are based on information available in the public domain; information was retrieved from a limited search of the grey literature. Drug plans were selected based on the anticipation that the reimbursement criteria they use would be generalizable to the Canadian context. The findings of this report are also subject to interpretation of the translation of non-English information found on websites and documents.

ConclusionMany international publicly funded drug plans reimburse all four DOACs for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, publicly funded drug plans in the US require additional criteria for some DOACs (non-preferred drugs) to be reimbursed. Most publicly funded drug plans reimburse DOACs based on specific clinical criteria, many of which are risk factors used in calculating the CHADS2 score. Risk stratification scores are not commonly used as part of the reimbursement criteria for DOACs by international publicly funded drug plans or private plans in the US. In cases where the CHADS2 or CHA2DS2-VASc scores are used as part of the reimbursement criteria, it does not appear that one score is used more than the other. CHAD65 was not identified in any of the adjudication information for the reimbursement of DOACs.

Complementing this Environmental Scan, CADTH prepared a Rapid Response in 2017 reviewing the clinical effectiveness and guidelines of risk stratification scoring systems (including CHADS2, CHAD65 and CHA2DS2-VASc) in patients with atrial fibrillation. This report is available free of charge on the CADTH website.13


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4. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991 Aug;22(8):983-8.

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