Cross-Canada Collaboration to

Promote Evidence-Based Use of

Anticoagulants

CADTH SYMPOSIUM

APRIL 14, 2015

Speakers

Sarah Jennings, BSc, BScPhm, RPh, PharmD

Knowledge Mobilization Officer, CADTH

Lynette Kosar, BSP, MSc (Pharm)

Information Support Pharmacist, RxFiles Academic Detailing

Isobel Fleming, BScPharm, ACPR

Director of Academic Detailing Service, Dalhousie

Bronwen Jones, MD, CCFP

Director of Evidence Based Medicine, Dalhousie

Cait O’Sullivan, PharmD, BScPh, BA

Clinical Pharmacist, BC Provincial Academic Detailing Service

• 350,000 Canadians have A-fib.

• They are 3 to 5 times more likely to have a stroke.

• Most need lifelong anticoagulant therapy.

• Warfarin (Coumadin) has been the mainstay of

therapy for many years.

• Newer oral anticoagulants (NOACs) approved in

Canada for stroke prevention in people with atrial

fibrillation:

• dabigatran (Pradaxa)

• rivaroxaban (Xarelto)

• apixaban (Eliquis)

Warfarin NOACMany indications Limited indications

Individualized dosing

Regular INR monitoring

Multiple fixed doses

INR monitoring not required

Drug interactions Fewer drug interactions

Less studied

Long half-life Short half-life

Antidote is Vitamin K No antidote, and no proven way to reverse anticoagulation effects if bleeding occurs

CADTH Systematic ReviewAbsolute risk reduction per 1,000 patients treated each year

Stroke / Systemic

Embolism

Major bleeding

Intracranial bleeding

Major GI bleeding

MIMortality

dabigatran 110 mg

2 fewer(2 more, 4 fewer)

7 fewer(2 fewer,11 fewer)

5 fewer(4 fewer,6 fewer)

1 more(4 more,1 fewer)

2 more(5 more,0 more)

3 fewer(2 more,8 fewer)

dabigatran150 mg

6 fewer(3 fewer,8 fewer)

2 fewer(3 more,6 fewer)

4 fewer(3 fewer,5 fewer)

4 more(8 more,1 more)

2 more(5 more,0 more)

4 fewer(0 more,9 fewer)

rivaroxaban3 fewer(1 more,6 fewer)

1 more(6 more,3 fewer)

3 fewer(1 fewer,4 fewer)

8 more(13 more,4 more)

2 fewer(1 more,4 fewer)

4 fewer(2 more,8 fewer)

apixaban3 fewer

(1 fewer,5 fewer)

8 fewer(6 fewer,11 fewer)

4 fewer(3 fewer,5 fewer)

1 fewer(1 more,2 fewer)

1 fewer(1 more,2 fewer)

4 fewer(0 more, 8

fewer)

Results – TTR > 66%

Statistically significant reduction relative to adjusted dose warfarin?

Stroke / SystemicEmbolism

Major bleeding

dabigatran 110 mg1 fewer

(3 more, 5 fewer)4 fewer

(2 more, 10 fewer)

dabigatran 150 mg3 fewer

(2 more, 6 fewer)5 more

(13 more, 2 fewer)

rivaroxaban5 fewer

(2 more, 10 fewer)11 more

(25 more, 0 more)

apixaban3 fewer

(1 more, 5 fewer)6 fewer

(0 more, 10 fewer)

Approximate Daily Costs

Warfarin with monitoring

~$1

NOAC

~$3

Warfarin

$0.06

CADTH messages

• Warfarin is the recommended first-line therapy for

preventing stroke in patients with atrial fibrillation.

• New oral anticoagulants are a second-line option for some

patients with non-valvular atrial fibrillation not doing well on

warfarin.

• If a new oral anticoagulant is prescribed, patients must be

monitored.

• For people who are able to use an anticoagulant,

anticoagulant drugs should be used in preference to

antiplatelet drugs.

On slideshare: http://www.slideshare.net/CADTH-ACMTS/fmf2013-debate-cox-andcarrier

What is academic detailing?

Education on anticoagulants:

a priority across Canada

For More Information

www.cadth.ca/clots

Sarah Jennings

sarahj@cadth.ca

EXTRA SLIDES

prn

What is the CHADS2 Score?

CHADS2 Risk Criteria Score

Congestive heart failure 1

Hypertension 1

Age > 75 years 1

Diabetes mellitus 1

prior Stroke or TIA 2

CHADS2 Score Determination

Gage BF, et al. Validation of Clinical Classification Schemes for Predicting Stroke: Results From the National Registry of Atrial

Fibrillation. JAMA 2001;285(22):2864-2870.

• A common method of estimating stroke risk in patients with A-fib

CHADS2 score correlates with

stroke risk.

Points Annual Stroke Risk 95% Confidence Interval

0 1.9% 1.2-3.0

1 2.8% 2.0-3.8

2 4.0% 3.1-5.1

3 5.9% 4.6-7.3

4 8.5% 6.3-11.1

5 12.5% 8.2-17.5

6 18.2% 10.5-27.4

CHADS2 Risk Score and Corresponding Risk for Stroke in AF Patients

Not Treated With Anticoagulant Therapy

Gage BF, et al. Validation of Clinical Classification Schemes for Predicting Stroke: Results From the National Registry of Atrial

Fibrillation. JAMA 2001;285(22):2864-2870.

ISMP Report –

Adverse events reported to FDA

ISMP QuarterWatch. May 31, 2012. https://www.ismp.org/quarterwatch/pdfs/2011Q4.pdf

NOAC pivotal trials

Trial Characteristics RE-LY ROCKET-AF ARISTOTLE

Intervention / Comparator

dabigatran (110 mg or 150 mg) twice daily vs warfarin

rivaroxaban 20 mg once daily vs warfarin

apixaban 5 mg twice daily vs warfarin

Randomized Sample Size

18,113 14,264 18,201

Median follow-up 2 years 1.9 years 1.8 years

Age 71.5 years 73 years 70 years

Prior stroke/TIA ~20% ~55% ~20%

CHADS2 score 2.1 3.4 2.1

Time in therapeuticrange (TTR)

64% 55% 62%

Network Meta-Analysis (NMA)

• Absolute risk reductions compared to warfarin are small:

• 2 to 6 fewer strokes and systemic embolism per 1000 patients treated per year

• 1 more to 8 fewer major bleeding events per 1000 patients treated per year

• Relative cost-effectiveness of the new agents is uncertain:

• depends on pricing of the new agents

• varies according to patient population

• heterogeneity of the underlying clinical data

Expert Committee Deliberations

CADTH Current Practice report

Findings – health professionals:

• Warfarin usually started by

specialists, managed by family

MDs

• Most are not using dosing tools

• Patient education a team effort?

• Specialists most open to the new

agents

• Family MDs and allied health

more cautious

CADTH Current Practice report

Findings – patients:

• Satisfied with therapy, mixed in

openness to taking new drugs

• Acknowledge inconvenience, but

liked regular contact

• Felt confident in their level of

knowledge, but actually had a

limited understanding of warfarin

therapy:

• MOST did not know they were taking warfarin to prevent stroke.

• MANY attributed benefits or side effects to warfarin that were

unlikely to be due to the drug.

Warfarin Therapy –

Knowledge and Practice Gaps

A well-coordinated, structured approach to warfarin therapy is

recommended BUT:

The approach to warfarin therapy is sometimes “casual” or “ad

hoc” with no definitive care plan

Dosing tools are an important part of a well-coordinated, structure

approach to warfarin therapy BUT:

Most specialists and Family MDs are not using them

Patient education is a component of a well-coordinated, structured

approach to warfarin therapy

Health professionals believe they are doing a good job of

educating their patients about warfarin BUT

Patients’ level of understanding is quite low

What is a structured plan?

Warfarin Management Plan Checklist

Things to consider when developing a structured plan of care:

Patient Follow-up

INR Monitoring

Dose adjustments (including dosing tool)

Monitoring for complications/side effects

Other health professionals involved in care/patient education

Caregiver engagement

Patient Education – ongoing

NOAC monitoring

• Indication

• Renal function

• Drug interactions

• Bleeding risk

• Patient education

• Compliance, compliance, compliance

Warfarin Clinical & Economic Reports

Bottom Line:

• Unclear whether specialized anticoagulation clinics result

in improved clinical outcomes compared with usual care.

• Evidence on patient self-testing/management was mixed,

but they may lead to improvements in some patient

outcomes.

• Uncertainty in terms of cost and cost-effectiveness.

Optimizing Warfarin Therapy –

Recommendations

• The COMPUS Expert Review Committee (CERC)

recommends:

• Patients with NVAF requiring warfarin be managed by a well-

coordinated, structured approach dedicated to their anticoagulation

therapy.*

• *Does not need to be restricted to specialized anticoagulation clinics.

• CERC does not recommend:

• Self-management for most patients with NVAF requiring warfarin.

• CERC determined:

• There is no evidence to make a recommendation on the role of

warfarin management options in remote areas.

NVAF (non-valvular atrial fibrillation)