Cross-Canada Collaboration to Promote Evidence-Based Use of
Anticoagulants
CADTH SYMPOSIUMAPRIL 14, 2015
Speakers
Sarah Jennings, BSc, BScPhm, RPh, PharmDKnowledge Mobilization Officer, CADTH
Lynette Kosar, BSP, MSc (Pharm)Information Support Pharmacist, RxFiles Academic Detailing
Isobel Fleming, BScPharm, ACPRDirector of Academic Detailing Service, Dalhousie
Bronwen Jones, MD, CCFPDirector of Evidence Based Medicine, Dalhousie
Cait O’Sullivan, PharmD, BScPh, BAClinical 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 indicationsIndividualized dosingRegular INR monitoring
Multiple fixed doses INR monitoring not required
Drug interactions Fewer drug interactionsLess studied
Long half-life Short half-lifeAntidote 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
MI Mortality
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)
dabigatran 150 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 / Systemic Embolism Major bleeding
dabigatran 110 mg 1 fewer(3 more, 5 fewer)
4 fewer(2 more, 10 fewer)
dabigatran 150 mg 3 fewer(2 more, 6 fewer)
5 more(13 more, 2 fewer)
rivaroxaban 5 fewer(2 more, 10 fewer)
11 more(25 more, 0 more)
apixaban 3 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
EXTRA SLIDES
prn
What is the CHADS2 Score?
CHADS2 Risk Criteria ScoreCongestive 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 Interval0 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 yearsAge 71.5 years 73 years 70 yearsPrior stroke/TIA ~20% ~55% ~20%CHADS2 score 2.1 3.4 2.1
Time in therapeutic range (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)