1 CHARLOTTETOWN, PEI • CPhA 2013 FINAL PROgRAm

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MOnday,JUnE 3

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CPhA 2013

conference 2013conference 2013June 1-4 • Charlottetown, PEIDelta Prince Edward Hotel & Charlottetown Civic Centre

Charlottetown Rocks!

New Oral Anticoagulant Therapy: Is Newer Better? William (Bill) Semchuck, MSc,PharmD,FCSHP Manager, Pharmacy Practice Regina Qu’Appelle Health Region Bill Semchuk is the Manager of Pharmacy Practice in the Regina Qu’Appelle Health Region. His practice, education and research interests revolve around the areas of Cardiovascular Risk Reduction and Thrombosis and the roles that medications play in those areas. Bill received his baccalaureate and masters degrees from the University of Saskatchewan and his doctor of pharmacy degree from Purdue University, West Lafayette, Indiana. He is an Assistant Clinical Professor at the College of Pharmacy and Nutrition as well as the College of Medicine, Univ of Sask. Clinically Bill works in the Lipid Clinic and the Anticoagulation Clinic. He is an active member of numerous professional groups including the Canadian Cardiovascular Pharmacist Network and the Thrombosis Interest Group of Canada. Learning Objectives:

• To discuss the evolution in availability of anticoagulants • To review clinical trial data pertaining to the novel oral anticoagulant agents • To discuss clinical considerations in the use of these agents • To discuss the role of the pharmacist in the management of patients receiving

anticoagulant therapy Description: The therapeutic options to manage patients with and at risk of thrombotic events have changed dramatically over the past 4 years. Clinicians and patients are challenged to choose the best agent to decrease the risk as well as morbidity and mortality associated with thrombosis and its treatment. By reviewing clinical trial data, pharmacokinetic and phamacodynamic information and applying that to patient/client situations, decisions can be made in concert with patient’s input. Pharmacists can play a key role in aiding in appropriate use of these agents

New Oral Anticoagulant Therapy: Is Newer Better?

Wm Semchuk, MSc, PharmD, FCSHP Manager, Pharmacy Practice Regina Qu’Appelle Health Region

Learning Objectives

• To discuss the evolution in availability of anticoagulants

• To review clinical trial data pertaining to the novel oral anticoagulant agents

• To discuss clinical considerations in the use of these agents

• To discuss the role of the pharmacist in the management of patients receiving anticoagulant therapy

Conflict of interest disclosure:

Company Involvement

1. Boehringer Ingelheim - Advisory Board and Honoraria 2. Sanofi Aventis - Advisory Board, Honoraria and

Research Grants 3. BMS - Advisory Board, Honoraria

4. GSK - Honoraria

5. Bayer - Advisory Board, Honoraria

6. Pfizer - Advisory Board, Honoraria

7. Astra Zeneca - Advisory Board, Honoraria

3

Parenteral

Oral

1910 2010 1960 1950 1940 1930 1920 1970 1980 1990 2000

Heparin

Warfarin

LMWH’s

Direct Thrombin Inhibitors

Indirect FXa Inhibitors

Direct Thrombin Inhibitors

Direct FXa Inhibitors

Adapted from: Weitz J, Hirsh J. Chest. 2001;119:95S; Alban. Eur J Clin Invest 2005; Link. Circulation 1959; Maraganore et al. Biochemistry 1990

Timeline of Anticoagulation Options

2008 2011 2010 2009

Dabigatran VTE prophylaxis following THR/TKR

Health Canada Approvals of New Oral Anticoagulants

Rivaroxaban VTE prophylaxis following THR/TKR

Apixaban VTE prophylaxis following THR/TKR

Dabigatran Stroke prevention in AF

Apixaban Stroke prevention in AF

Rivaroxaban Treatment of DVT

2013 2012

Rivaroxaban Stroke prevention in AF

Health Canada NOC database: http://webprod5.hc-sc.gc.ca/noc-ac/index-eng.jsp

6

Why the Excitement and why the rapid uptake: The promise of new oral anticoagulants

Improved compliance

Improved efficacy

and safety

Less impact on patients’ daily

life

Improved quality of life

Less labour-

intensive

Reduced administrative

costs

Reduced potential for food and drug

interactions

Simplified dosing regimen No dietary restrictions Predictable anticoagulation and no need

for routine coagulation monitoring Can be given at fixed doses

1. Raghaven N et al. Drugs Metab Dispos 2009;37:74–81; 2. Shantsila E & Lip GY. Curr Opin Investig Drugs 2008;9:1020–1033; 3. Mueck W et al. Clin Pharmacokinet 2008;47:203–216; 4. Mueck W et al. Thromb Haemost 2008;100:453–461; 5. Mueck W et al. Int J Clin Pharmacol Ther 2007;45:335–344

Anticoagulant Prescription Volume in Canada

Oral Anticoagulants

Rivaroxaban

Apixaban

Xa

IIa

TF/VIIa

X IX

IXa VIIIa

Va

II

Fibrin Fibrinogen

Adapted from Turpie Eur Heart J 2008; 29:155

Dabigatran

Warfarin site of action

New Oral Anticoagulants • Direct Thrombin Inhibitors:

– Dabigatran (Pradax® - now Pradaxa®)

• Direct F Xa Inhibitors: – Rivaroxaban (Xarelto®) – Apixaban (Eliquis®) – More to come…..

New Orals: Approved Indications • Approved for use in Canada (May 2013)

–Prophylaxis for elective hip and knee orthopedic surgery (dabigatran, rivaroxaban and apixaban)

–Atrial fibrillation (dabigatran, rivaroxaban, apixaban)

–Treatment of Deep Vein Thrombosis (non symptomatic PE), Treatment of PE (rivaroxaban)

11

Thromboprophylaxis with Rivaroxaban after THR/TKR: Primary efficacy outcome: composite of any DVT, nonfatal PE, or death from any cause

P<0.001

Inci

denc

e (%

)

Eriksson BI,et al. N Engl J Med. 2008;358(26):2765-75.; Kakkar AK, et al. Lancet. 2008;372 (9632):31-39. Lassen MR, et al. N Engl J Med. 2008;358(26):2776-2786;Turpie A, et al. Lancet. 2009 May 16;373(9676):1673-80. Epub 2009 May 4.

P<0.001

P<0.001

P<0.012

TOTAL HIP REPLACEMENT (THR) TOTAL KNEE REPLACEMENT (TKr)

PE: Pulmonary embolism

12

Thrromboprophylaxis with Rivaroxaban after THR/TKR: Major Bleeding Endpoint

Inci

denc

e (%

)

Eriksson BI,et al. N Engl J Med. 2008;358(26):2765-75.; Kakkar AK, et al. Lancet. 2008;372 (9632):31-39. Lassen MR, et al. N Engl J Med. 2008;358(26):2776-2786; Turpie A, et al. Lancet. 2009 May 16;373(9676):1673-80. Epub 2009 May 4.

P=NS

P=NS

P=NS

P=NS

P=0.0003 for non-inferiority

RE-MODEL RE-MOBILIZE † RE-NOVATE

P=0.017 for non-inferiority

P<0.0001 for non-inferiority

P<0.0001 for non-inferiority

Thromboprophylaxis with Dabigatran following THR/TKR: Primary Efficacy Outcome: Total VTE or All-Cause Mortality

13

(Hip) (Knee)

Dabigatran

Enoxaparin

Eriksson et al. J Thromb Haemost 2007; Ginsberg et al. J Arthroplast. DOI:10.1016/j.arth.2008.01.132; Eriksson et al. Lancet 2007

P=0.02 *

* P-value that the margin of 9.2% as the upper limit of the 95% CI for ARD was exceeded

P=0.0009 *

† Confidence intervals not reported

14 1.Eriksson BI, et al. 2007 Lancet. 2007;370:949-956; 2. Eriksson BI, et al. J Thromb Haemost. 2007;5(11):2178-2185; 3. The RE-MOBILIZE Writing Committee J Arthroplasty. 2009 Jan;24(1):1-9. Epub 2008 Apr 14.

RE-NOVATE (THR) RE-MODEL (TKR)

RE-MOBILIZE (TKR)

P=NS

P=NS

VTE Prophylaxis with Dabigatran after THR/TKR: Major Bleeding Endpoint

P=NS

Apixaban Enoxaparin

Thromboprophylaxis with Apixiban after THR/TKR: Efficacy and Safety

Efficacy: Any VTE / All-Cause Death Safety: Major or CRNM Bleeding

Enox Dose:

Even

ts (%

)

0

5

10

15

20

25

30

Even

ts (%

)

0

1

2

3

4

5

6

7

40 QD

ADVANCE-2 TKR

P=0.09

3.5

4.8

ADVANCE-2 TKR

15.1

24.4

40 QD

P<0.0001

ADVANCE-1 TKR

P=0.03

ADVANCE-1 TKR

2.9

4.3

30 BID

ADVANCE-3 THR

P<0.0001

1.4 3.9

ADVANCE-3 THR

4.8 5.0

P=0.072

P=0.06

8.8 9.0

30 BID Lassen MR. NEJM 2009;361:594. Lassen MR Lancet 2010;375:875 Lassen MR. NEJM 2010;363:26:2487

Current Status • Dabigatran, Rivaroxaban and Apixaban approved

in Canada for the prevention of VTE in patients undergoing elective THR or TKR

– Rivaroxaban approved by CDR Dec 08

– Dabigatran not recommended by CDR Jan 09

– Apixaban approved by CDR June 2012

• In general – this is short term therapy and these will generally be used for approximately 14 days for TKR and 30 days for THR

16

Atrial Fibrillation Major Risk Factor for Stroke

• Independent risk factor for stroke - increases the risk of stroke by 5-fold1,2,3

• Accounts for approximately 15-20% of all strokes nationally1,4

• Risk of stroke in AF patients by age group – 1.5% in 50–59 year olds – 23.5% in 80–89 year olds

• Risk of stroke is the same in AF patients regardless of whether they have paroxysmal or sustained AF

1.Atrial Fibrillation Investigation Group. Arch Intern Med. 1994 2. Wolf PA, et al. Stroke 1991

3. Savelieva I, et al. Ann Med 2007 4. Singer DE, et al. Chest 2008 AF=atrial fibrillation

Warfarin vs Placebo Relative RR vs. placebo 64% (CI 49–74%) Absolute RR primary 2.7%/yr Absolute RR secondary 8.4%/yr Major extracranial bleeding 31 vs. 17 (ARR -0.3%/yr)

100% 50% 0 -50% -100%

Favours Warfarin Favours Placebo or Control

Adjusted-dose warfarin compared with placebo or control

AFASAK I, 1989; 1990

SPAF I, 1991

BAATAF, 1990

CAFA, 1991

SPINAF, 1992

EAFT, 1993

All trials (n=6)

A Study, Year Relative Risk Reduction (95% CI)

Antiplatelet vs. Placebo Relative RR vs. placebo 19% (CI -1–35%) Absolute RR primary 0.8%/yr Absolute RR secondary 2.5%/yr Major extracranial bleeding 16 vs. 15 (ARR -0.2%/yr)

100% 50% 0 -50% -100% Favours Antiplatelet Favours Placebo

or Control

Antiplatelet agents compared with placebo or control

B Study, Year Relative Risk Reduction (95% CI)

AFASAK I, 1989; 1990 SPAF I, 1991 EAFT, 1993 ESPS II, 1997 LASAF, 1997

Daily Alternate day

UK-TIA, 1999 300 mg daily 1200 mg daily

JAST, 2006

Aspirin trials (n=7)

SAFT, 2003 ESPS II, 1997

Dipyridamole Combination

All antiplatelet trials (n=8)

Hart et al. Ann Intern Med 2007;146(12):857

Warfarin vs Antiplatelet Relative RR 37% (CI 23–48%) Absolute RR primary 0.9%/yr Major extracranial bleeding 40 vs. 22 (ARR -0.2%/yr) Intracranial haemorrhage 20 vs. 7 (ARR -0.2%/yr)

100% 50% 0 -50% -100% Favours Warfarin Favours Antiplatelet

Adjusted-dose warfarin compared with antiplatelet agents

AFASAK I, 1989; 1990

C Study, Year Relative Risk Reduction (95% CI)

AFASAK II, 1998 Chinese ATAFS, 2006 EAFT, 1993 PATAF, 1999 SPAF II, 1994

Age ≤75 y Age >75 y

SIFA, 1997

Aspirin trials (n=8)*

ACTIVE-W, 2006 NASPEAF, 2004

All antiplatelet trials (n=11)

Relative Effects of Antithrombotic Therapies on All Stroke From Randomised Trials in AF

18

NOACs in AF

• 3 large trials have been published that have compared these agents to warfarin – RELY – Dabigatran – ROCKET – Rivaroxaban – ARISTOTLE – Apixaban

• Warfarin was very well utilized in these trials (much better than you would expect in clinical practice)

Comparison of NOAC AF Studies Parameter RELY (dabigatran

etexilate) ROCKET (rivaroxaban)

ARISTOTLE (apixaban)

Design Blinded dabigatran but open-label warfarin (NI)

Double-blind, event driven (NI)

Double-blind, event driven (NI)

Comparators Warfarin vs Dabigatran 110 bid Dabigatran 150 bid

Rivaroxaban 20 mg daily (15 mg daily for CrCl 30-49 ml/Min

Apixaban 5 mg bid (2.5 mg bid if > age > 80, wt < 60kg, Creat > 133 umol/L

Primary efficacy outcome

Stroke (I or H) or systemic embolism

Stroke (I or H) or systemic embolism

Stroke (I or H) or systemic embolism

Primary safety outcome

Major bleeding Major + NMCR bleeding

Major bleeding

Connolly NEJM 2009;361:1139; Patel NEJM 2011;365:883; Granger NEJM 2011;365:981

Comparison of NOAC AF Studies

Parameter RELY ROCKET ARISTOTLE

N 18,113 14,264 18,201

CHADS2 score, mean + SD

2.1 + 1.1 3.5 + 1.0 2.1 + 1.1

Warfarin TTR, mean

64% 55% 62.2%

Reduced dose of intervention drug

1.1% 4.7%

Comparison of NOAC AF Studies

Parameter RELY ROCKET ARISTOTLE

Primary efficacy outcome (ITT analysis)

W 1.7%/yr D110 1.5% yr D150 1.1% yr RR: D110-W 0.91 (0.74-1.11) D150 – W 0.66 (0.53 -0.82)

W 2.4%/yr R 2.1%/yr HR: 0.88 (0.74-1.03)

W 1.6%/yr A 1.3%/yr HR: 0.79 (0.66-0.95)

Death ITT W 4.1/yr D110 3.8%/yr D150 3.6%/yr

Safety pop: W 2.2%/yr R 1.9%/yr

ITT W 3.9%/yr A 3.5%/yr

Comparison of NOAC AF Studies

Parameter RELY ROCKET ARISTOTLE

Major Bleeding

W 3.4%/yr D110 2.7%/yr (p=0.003)

D150 3.1%/yr (p=0.31)

W3.4%/yr R3.6%/yr HR: 1.04 (0.90-1.20)

W3.1%/yr A2.1%/yr HR: 0.69 (0.60-0.80)

Intracranial bleeding

W 0.7%/yr D110 0.2%/yr D150 0.3%/yr

W 0.7% R 0.5% HR: 0.67 (0.47-0.93)

W 0.8%/yr A 0.3/yr HR: 0.42 (0.30 -0.58)

Our Current Pharmacologic Options for AF Stroke Reduction

24 Granger. Circ 2012;125:159-164

INR Control: Clinical Trials vs. Clinical Practice

1 Kalra et al. BMJ 2000 2 Matchar et al. Am J Med 2002

3 Bungard et al. Pharmacotherapy 2000

TTR = Time in Therapeutic Range (INR2.0-3.0) INR = International Normalized Ratio

INR control is an ongoing challenge in routine clinical practice

25

66

9

38 44

18

45 37

18 0

10 20 30 40 50 60 70

INR < 2.0 INR 2.0 - 3.0 INR >3.0

% o

f elig

ible

pat

ient

s

rece

ivin

g w

arfa

rin

Clinical Trial Clinical Practice Clinical Practice

1

2

3

The Importance of Effective INR Control

• 3587 patients randomized to warfarin (INR 2-3) in SPORTIF III & V

• Mean follow-up (± SD) of 16.6 ± 6.3 months

White et al. Arch Intern Med 2007

Poor Control TTR<60% N=1190

Moderate Control TTR 60-75%

N=1207

Good Control TTR>75% N=1190

# Risk Factors (%) 1 2 >3

28.5 30.3 41.2

30.1 29.6 40.3

29.1 35.7 35.2

Mortality (%/year) 4.20 1.84 1.69

Stroke / systemic embolism (%/year) 2.10 1.34 1.07

Major bleeding (%/year) 3.85 1.96 1.58

Dabigatran, Rivaroxaban and Apixaban

• Published data available for all three • Dabigatran, Rivaroxaban, Apixaban – Health

Canada Indication for Prevention of Stroke and Systemic Embolism

• All have positive reviews by CDR

27

VTE: Deep Vein Thrombosis and Pulmonary Embolism

PE

Migration Embolus

Thrombosis is the formation or presence of a thrombus that may obstruct blood flow through a vein or artery1

VTE occurs when thrombosis obstructs blood flow through a vein

The term VTE encompasses:

DVT

PE

1. Anderson FA, et al. Center for Outcomes Research, University of Massachusetts Medical Center; 1998 2. Goldhaber SZ. J Am Coll Cardiol 1992;19:246–247 DVT, deep vein thrombosis; PE, pulmonary embolism

As the venous clot grows, it extends along the vein

PE occurs when parts of the clot detach and travel in the blood to block vessels in the lungs

Thrombus

The Risk of Recurrent VTE

• Overall incidence of recurrent VTE at 6 months is 7%, despite anticoagulant therapy – After an initial DVT, ~80% of the recurrences are DVTs2

– After an initial PE, ~60% of the recurrences are PEs2

1. Line B. Semin Nucl Med. 2001;31:90–101 2. Kearon C. Circulation 2003;107:I22–I30

Events occurring subsequent to an acute episode are termed recurrent VTE, and their prevention is termed secondary prevention

Chance of recurrent VTE in first 3 months

47% If proximal DVT inadequately treated1

<2% If adequate anticoagulant response is

achieved1 (2-4% in subsequent 3 months)

NOACs in VTE

• Studied and published approaches: – IV LMWH followed by NOAC (dabigatran) – IV LMWH + VKA vs NOAC started initially

(rivaroxaban) – Standard therapy followed by extension therapy

(active vs placebo) (dabigatran, rivaroxaban and apixaban)

– Currently only rivaroxaban with a Health Canada Indication

Rivaroxaban in the Treatment of VTE: EINSTEIN Trial (DVT & PE Trials)

• Open-label, event-driven, non-inferiority trials

15 mg bid

Confirmed symptomatic

DVT

without symptomatic

PE

N=3,449 Rivaroxaban

Day 1 Day 21

Enoxaparin (1.0 mg/kg) bid for at least 5

days,

plus VKA target INR 2.5 (INR range 2–3)

20 mg od Rivaroxaban

R

30-d

ay o

bser

vatio

n pe

riod

15 mg bid Confirmed

symptomatic PE

with or without

DVT

N=4,833 Rivaroxaban

Day 1 Day 21

Enoxaparin (1.0 mg/kg) bid for at least 5

days,

plus VKA target INR 2.5 (INR range 2–3)

20 mg od Rivaroxaban

R

30-d

ay o

bser

vatio

n pe

riod

Ineligible if LMWH > 48H, >1 warfarin dose, treatment with thrombectomy, IVC filter, lytics, CI to drugs

Exclusions: Another indication for warfarin; CrCL < 30 mL/min; clinically significant hepatic disease; bacterial endocarditis; active bleeding / high bleed risk; SBP>180 mmHg or DBP>110mmHg; lack of birth control, pregnant, breast feeding; strong P-450 3A4 inducers/inhibitors; life expectancy < 3 months

EINSTEIN: Primary efficacy outcome analysis

Rivaroxaban (n=1,731)

Enoxaparin/VKA (n=1,718)

n (%) n (%) First symptomatic recurrent VTE 36 (2.1) 51 (3.0)

Recurrent DVT 14 (0.8) 28 (1.6) Recurrent DVT + PE 1 (<0.1) 0 (0) Non-fatal PE 20 (1.2) 18 (1.0) Fatal PE/unexplained death where PE cannot be ruled out

3 (0.2) 6 (0.3)

p<0.001 for non-inferiority (one-sided)

1.00 0

0.44 1.04 0.68

Hazard ratio

p=0.076 for superiority (two-sided)

2.00

ITT population EINSTEIN Investigators. N Engl J Med 2010 32

EINSTEIN: Principal safety outcome analysis

Rivaroxaban (n=1,718)

Enox/VKA (n=1,711) HR (95% CI)

n (%) n (%) p value First major or clinically relevant non-major bleeding

139 (8.1) 138 (8.1) 0.97 (0.76–1.22) p=0.77

Major bleeding 14 (0.8) 20 (1.2) 0.65 (0.33-1.30)

p=0.21

Contributing to death 1 (<0.1) 5 (0.3)

In a critical site 3 (0.2) 3 (0.2)

Associated with fall in Hb ≥2 g/dL and/or transfusion of ≥2 units 10 (0.6) 12 (0.7)

Clinically relevant non-major bleeding

126 (7.3) 119 (7.0)

EINSTEIN Investigators. N Engl J Med 2010

Safety population 33

VTE Summary

• Data published • Rivaroxaban Health Canada Approved for

DVT without symptomatic PE as well as PE • Rivaroxaban CDR Approved for DVT

without symptomatic PE Aug 2012 • Dabigatran – no Health Canada approval

yet • Apixaban – no Health Canada approval yet

34

Looking at the drugs further:

• Pharmacologic/PK/PD • Clinical Scenarios:

– Renal dysfunction – Bridging – Monitoring – Bleeding

New Oral Agents – key considerations Rivaroxaban Apixaban Dabigatran

Time to Cmax (hrs) 2.5 to 4 3 2.3-2.9

Half-life (hrs) 5.7-9.2 8-14 14-17

Renal clearance 33% (of active drug) (50% of metabolized inactive drug)

25% 80%

Hepatic clearance 33% (of total) 20%

Prodrug No No Yes

Bioavailability 80% 50% 5%

Antidote? No No No

Potential DIs PGP and Cyp3A4 PGP and Cyp3A4 PGP

Safe in pregnancy? No No No

Renal function decreases with age: this may be an issue with agents that are

primarily renally excreted

1.Cook et al. J Thromb Haemost 2007;5:937-41.

Mean creatinine clearance in patients with VTE1

Age group

Cre

atin

ine

clea

ranc

e (m

L/m

in-1

)

Practice Point: Need to assess renal function prior to initiating these agents and continue to monitor through the treatment period

0

20

40

60

80

100

120

<75 years >75 years >80 years >90 years

37

Dabigatran Rivaroxaban Apixaban

CrCl > 80 mL/min 13.8 hr 8.3 hr 12 hr

CrCl 50-79 mL/min

16.6 hr (AUC ↑ 1.5 fold)

8.7 hr (AUC ↑ 44%)

AUC ↑ 16%

CrCl 30-49 mL/min

18.7 hr (AUC ↑ 3.2 fold)

9 hr (AUC ↑ 52%)

AUC ↑ 29%

CrCl < 30 mL/min 27.5 hr (AUC ↑ 6.3 fold)

9.5 hr (AUC ↑ 64%)

AUC ↑ 44%

ESRD (hemodialysis)

34.1 hr

Br J Clin Pharmacol 2010;70(5):703-712, Clin Pharmacokinet 2010;49(4):259-268, Eliquis Product Monograph 2011.

CrCl 30-50 mL/min

• RELY – No dose adjustment – No significant interaction with thrombotic

outcome but trend to bleeding benefit (cw VKA)

• ARISTOTLE – Creatinine of 133 uM was one (of 3, need 2) to get

2.5 mg BID – No significant interaction with outcomes

• ROCKET – CrCl 30-50 ml/min at enrolment got 15 mg daily – No significant interaction with outcomes.

Drug Monitoring?

• Pre Invasive Procedures • Major Bleeding • Check Adherence or ? Adherence (e.g. new

event - VTE, stroke) • Potential Excess Accumulation:

– Renal and/or Hepatic Dysfunction – Drug Interactions (+ renal/hepatic dysfn)

Bleeding and Reversal • There is no known reversal agent • Strategies will be based on mechanistic results, very small

human studies using laboratory assessment as the endpoint, animal models

• Further data required • Strategies

• Red blood cells • Hydration • Treat source of bleeding (surgery, cauterization) • Charcoal if dosed in last 2 hours • Hemodialysis (rarely practical with hemorrhage) • Consult the local specialist ie. transfusion medicine to determine if the

following may be required: – ? Activated PCC (FEIBA) – ? PCC – ? VIIa

41

Post marketing Reports of Bleeding in New Users of Dabigatran and Warfarin from the

Mini-Sentinel Distributed Database, Oct 2010 – Dec 2011

Analysis Dabigatran Warfarin

Pt N # of events

Incidence (no of events /100,000 days at risk)

Pt N # of events

Incidence (no of events /100,000 days at risk)

GI Bleed* 10,5999 16 1.6 43451 160 3.5

ICH* 10587 8 0.8 43594 109 2.4

* Analysis with required diagnosis of AF

N Engl J Med 2013;368(14):1272-1274

What is the pharmacist’s role?

• Ensure the dose and the drug is correct to the indication

• Make sure that “therapeutic drift” is minimized • Assess renal function • Check for Drug Interactions • Educate patients about benefit, risk and what to do • Medic Alert/Pocket Card • Adherence

Population/ Duration

Rivaroxaban Apixaban Dabigatran

VTE Prevention, Orthopedic Surgery (generally 30 days or less)

10 mg daily 2.5 mg BID 220 mg daily

Stroke Prevention, Atrial Fibrillation (lifelong)

20 mg daily or

CrCl 30-50: 15 mg daily

5 mg BID or

2.5 mg BID (unclear HC indications)

150 mg BID or

110 mg BID

VTE Treatment (3 months to lifelong)

For DVT: 15 mg BID then

20 mg daily

Doses/Indications

Absolute Contraindications

• Mechanical valves – excess strokes with dabigatran – rivaroxaban and apixaban – not studied

• Significant valve disease – Excluded from studies

• Liver disease with elevated INR – No experience, can’t monitor

• Pregnancy – All NOACs cross the placenta

• CrCl < 30mL/min (limited experience with apixaban <15 mL/min

Relative Contraindications

• Venous thromboembolism in cancer patients – Small numbers of patients have been studied

• As treatment for Heparin-induced thrombocytopenia – Being studied

• Thrombocytopenia (don’t know cut-offs)

Effect on new oral anticoagulant plasma levels (area (AUC) from drug interactions and recommendations towards new oral anticoagulant dosing

Via Dabigatran Apixaban Edoxaban* Rivaroxaban

Atrovastatin P-gp Competition And CYP3A4

Inhibition

+18% No data yet No effect No effect

Digoxin P-gp Competition

No effect No data yet No effect No effect

Verapamil P-gp competition

+12-180% (reduce dose and take

simultaneously)

No data yet

+53% (SR) (Reduce dose by

50%)

Minor effect (use with caution

if CrCl 15-50 ml/min)

Diltiazem P-pg competition and weak CYP3A4

inhibition

No effect +40% No data yet Minor effect (use with caution if Crcl

15-50 ml/min)

Quinidine P-gp Competition

+50% No data yet +80% (Reduce dose

by 50%)*

+50%

Amiodarone P-gp Competiton

+12-60% No data yet No effect Minor effect (use with caution if Crcl

15-50 ml/min)

Dronedarone P-gp and CYP3A4 inhibitor

+70-100% (US: 2 x 75mg)

No dat yet +85% (Reduce dose by

50%)*

No data yet

Ketoconazole; Itraconazole; Variconazole’ posaconazole

P-gp and BCRP Competition;

CYP3A4 inhibition

+140-150% (US: 2 x 75mg)

+100% No data yet Up to +160%

Red: CI or not recommended, Orange: Reduce dose, Yellow: consider dose reduction Europace 2013;15:625-651

Via Dabigatran Apixaban Edoxaban* Rivaroxaban

Fluconazole Moderate CYP3A4 inhibition

No data yet No data yet No data yet +42% (if systemically administered)

Cyclosporin; tacrolimus P-gp Competition

No data yet No data yet No data yet +50%

Clarithromycin; erythromycin

P-gp Competition and

CYP3A4 inhibition

+15-20% No data yet No data yet +30-54%

HIV protease inhibitors (e.g. ritonavir)

P-gp/BCRP and CYP3A4/CYP2J2

Inducers

No data yet Strong increase

no data yet Up to +153%

Rifampicin; St. John’s wort; carbamazepine;

phenytoin; phenobarbital

P-pg/BCRP and CYP3A4/CYP2J2

Inducers

-66% +54% -35% Up to -50%

Antancids (H2B; PPI; Al-Mg-hydroxide)

GI absorption -12-30% No data yet No effect

No effect

Other factors:

Age ≥ 80 Years Increased plasma level

No data yet

Age ≥ 75 years Increased plasma level

No data yet

Weight ≥ 50 kg Increased plasma level

Renal Function Increased plasma level

Other increased bleeding risk

Pharmacodynamics interactions (antiplatelet drugs; NSAID; systemic steroid therapy; Other anticoagulants); history or active GI bleeding; recent surgery on critical organ (brain; eye); thrombocytopenia (e.g. chemotherapy); HAS-BLED ≥3

Europace 2013;15:625-651 Red: CI or not recommended, Orange: Reduce dose, Yellow: consider dose reduction

Benefit vs Risk

• SPAF – 65-75% reduction in stroke – 2% major bleeds – 10-20% minor bleeds

• DVT – 10 fold or greater reduction in recurrent events – Similar (or slightly lower bleed rates than SPAF)

What to do with bleeds?

• Major: – Blood in urine, stool, vomiting blood – Go to ER

• Minor: – Nosebleeds – Bruising – Cuts – Mention to PCP

• Medic Alert bracelet or pocket card

Adherence

• Education: – What you are on and why – What to expect both good and bad and what to do about it – How long to take

• Educational materials • Adherence Reminders

– “RxmindMe Prescription” App – Provides automatic reminders to patients regarding when to take

medications; tracks number of doses remaining on Rx etc • Compliance Packaging • Discussion at every visit

Caveats with New Drugs

• New agents should not be assumed to be interchangeable with warfarin; each needs to be tested in specific situations –mechanical heart valves –antiphospholipid syndrome –cancer associated thrombosis –acute coronary syndromes –thrombosis in pregnancy

• Only loose guidelines available for perioperative management on these agents

• No antidote exists for any of them

Initiator of anticoagulant treatment:

⁻ Sets indication for anticoagulation; ⁻ Makes choice of anticoagulant; ⁻ Decides on need of proton pump inhibitor; ⁻ Baseline haemoglobin, renal and liver function; ⁻ Provides education; ⁻ Hands out anticoagulation card; ⁻ Organizes follow-up (when, by whom, what?); ⁻ Remains responsible coordinator for follow-up.

First FU: 1 month

Follow-up by primary care giver

-Checks: 1.Compliance (patient should bring remaining pills); 2.Thrombo-embolic events; 3.Bleeding event’ 4.Other side effects; 5.Co-medication and over-the-counter drugs. 6.Need for blood sampling? 1m?

3m 6m?

In case of problems; contacts initiator of treatment.

Else: fills out anticoagulation card an sets date/place for next follow-up.

Europace 2013;15:625-651

Considerations In Use

54

Clinical Evidence

Clinician Judgment

Patient Preference

• Efficacy and Safety data established in discrete populations • Gaps in knowledge • DIs? • Renal dysfunction ? • Special populations?

• Preference and difficulty in utilizing warfarin • Cost/Coverage

• Warfarin stability • Concurrent illness • Drug interactions • Reversibility • Volume of data • Adherence

Summary • The NOACs are becoming essential parts of our therapeutic

arsenal and have entrenched and expanding roles in a number of therapeutic indications: – VTE prophylaxis following orthopedic surgery – SPAF – VTE treatment

• Like any tool, these drugs need to be used wisely and clinicians will need to consider several scenarios prior to prescribing

• Adherence will be essential to ensure best outcomes and is likely best achieved by patient education and monitoring

• Due to the growth of information in this area, vigilance in ensuring the right drug, in the right dose for the right patient is essential 55

“ That’s all very well but does it kill rats?”

CBC Blogger ‘ robughblah’ response to Health Canada approval of dabigatran for stroke prophylaxis in those with atrial fibrillation, Nov

7th 2010

Questions?

56

Canadian Pharmacists Journal session: Translating Research Evidence into Australian Pharmacy Practice: Successes and Challenges

Brief Bio: Ines Krass

Ines Krass is Professor in Pharmacy practice in the Faculty of Pharmacy, the University of Sydney. Over recent years her research has focused on the development and implementation of disease state management programs (DSM) in Australian community pharmacy. She led a national research team which published the first Australian evidence supporting the role of the community pharmacist in caring for patients with diabetes, research which has informed the implementation of current professional services in Australian community pharmacy.

Presentation:

This presentation will give an overview of current professional pharmacy programs funded by the Australian government under the Fifth Community Pharmacy Agreement (5CPA) and trace some of the research which underpinned their development and implementation into practice. It will also highlight barriers and facilitators to service implementation from the perspectives of the pharmacy as an organisation and the stakeholders including pharmacists, general practitioners and consumers.

Learning Objectives:

1. Describe the professional pharmacy services currently offered through Australian Community pharmacies

2. Discuss the supporting evidence for HMR, MedsCheck, Diabetes Medscheck, Asthma and Diabetes DSM

3. Outline facilitators to service implementation

4. Identify important barriers to service implementation

Translating Research Evidence into Australian Pharmacy Practice: Successes and Challenges

Faculty of Pharmacy Professor Ines Krass

Presentation Outline

1. Australian Community pharmacy 2. Investment in research and

development 3. Examples of funded projects and

subsequent implementation 4. Lessons learned 5. 5CPA professional programs

Australian Bureau of Statistics: Population: 23,001,330. Number of Approved Pharmacies (2013): TOTAL 5,325 Approximate average population per pharmacy: 4320

Introduction: Some Key Statistics

Community Pharmacy Statistics

› The sector employed approximately 48,575 people

› The average community pharmacy dispenses 49,738 prescriptions a year

› In 2010, community pharmacies supplied183.9 million Pharmaceutical Benefits Scheme (PBS) scripts worth 7 billion Dollars, up from 2 million scripts in the previous year.

› Community pharmacies contribute an annual turnover of $13 billion

http://www.health.gov.au/internet/annrpt/publishing.nsf/content/strategic-directions-0506-2

Consumer Attitudes to Community Pharmacy

› 90% of Australian customers trust their pharmacist and believe their pharmacy is a quality healthcare destination.

› 82% consider their pharmacist an expert in medicines

› 79% believe pharmacy plays an important role in their healthcare management.

› 66% Australian customers go to their pharmacist before, or instead of, their GP for some minor medical conditions

Pfizer Australia Health Report, 2007 available at http://www.healthreport.com.au/Reports/37.pdf

Government Funding of Professional Programs

› 2001: funding for domiciliary medication reviews (HMR)

› 3rd Guild Government Agreement – 2000-2005 - $400 million for all professional programs (CMI, HMR,RMMR)

› 4th Guild Government Agreement 2006-2010- $566 million - Continuation of HMR and RMMR - New services – asthma, diabetes, DAA

› 5th Guild Government Agreement 2011-2015 - $508 million

Community pharmacy research investment

Principles underpinning R &D

Place of research in the overall health care

environment

Impact of research on the role of the pharmacist

Opportunities to influence policy and practice

Assessment of feasibility in the practice setting

Assessment of barriers and facilitators to uptake

Strategies to address known barriers

Home Medicines Review

A structured and collaborative health care service provided to patients living at home › HMR involves the consumer, their GP,

an accredited pharmacist and regular community pharmacy or other relevant members of the healthcare team

› The accredited pharmacist visits the consumer at their home, reviews their medicine regimen and routine

› Provides their GP with a report. › The GP and consumer then agree on a

medicine management plan. › Home Medicines Review

http://www.medicareaustralia.gov.au/provider/pbs/fifth-agreement/home-medicines-review.jsp

A

strokefoundation.com.au

HMR logo.gif

2CPA -HMR Research Chen et al, J Soc Adm Pharm, 1999; 3/4:134-144

Krass and Smith, Int J Pharm Pract 2000:8:111-120

275 patients 40% rate of change to medication regimen The estimated annual cost savings $222.43 for

implemented changes Gilbert et al, Med J Aust. 2002:177(4):189-92.

1000 patients 3 medication related problems per person Net saving of $120.00 per person

Some potential impacts of HMR

oReduced the number and cost of medications Krass I & Smith C Intl J Pharm Prac 2000; 8:111-120

oImprove medication appropriateness Castelino R et al, Ann Pharmacother. 2010;44: 1922-29.

oImprove drug knowledge and adherence Holland R et al.. Br J Clin Pharmacol 2008 Mar;65(3):303-16

oReduced time to next hospitalisation for warfarin induced bleeding in veterans Roughead EE et al. J Clin Pharm Ther. 2011 Feb;36(1):27-32.

oReduced time to next hospitalisation for heart failure veterans Roughead EE et al. Circ Heart Fail 2009; 2:424-8.

oReduced the number of falls in nursing home patients Zermansky AG Age and Aging 2006 Nov;35(6):586-91

11

Evidence inconclusive?

Chronic Disease Management in Community Pharmacy

1. Diabetes

2. Asthma

Research and Development

http://www.diabeteshealth.com/cartoons/type-2/

Chronology of Diabetes Research in Australia

15

Fourth Community Pharmacy Agreement

Diabetes Pilot Program – DMAS Stage 1

Third Community Pharmacy Agreement Krass et al, Diabetic Medicine 2007; 24:677-

683. I Krass, C Armour, B Mitchell et al.

Diabetes Research and Clinical Practice 2007;75: 3

Second Community Pharmacy Agreement

CL Armour et al. JAPhA 2004, 44:455-466. I Krass, SJ Taylor, C Smith. CL Armour. JAPhA

2005; 45(1): 35-40.

Diabetes care in community pharmacy

› Providing support of self blood glucose monitoring (SBGM),

› Monitoring and promoting patient adherence with medication and other components of self-management

› Identifying and resolving drug related problems

› Providing targeted information and explanations about diabetes and its management

› Motivating patients to take control › Reminding patients of the importance of

regular examinations for the presence of diabetic complications, e.g., eye and feet examinations.

16

The Diabetes Medication Assistance Service

Cycle of monitoring, review and feedback

Patient Behaviour change

Needs assessment

Goal Setting

Possible interventions

Monitoring and feedback

COMMUNITY PHARMACY DISEASE MANAGEMENT SERVICES

53%

72%

61%54%

0%

10%

20%

30%40%

50%

60%

70%

80%

Pre-intervention Post-intervention

Intervention (n=53)Control (n=46)

Final data collection at 9 months

Monthly followups for 9 months

At two weeks 2 nd visitCommence service

Enrol 135 patientsCollect Baseline Data

3 pharmacists in each setting(9 pharmacists)

Training in diabetes

Intervention Group (3 settings)Diabetes Clinic

RuralMetropolitan

Follow up data collection at 9 months

Enrol 135 patientsCollect Baseline Data

14 pharmacistsand a Diabetes Clinic

Control Group (3 settings)Diabetes Clinic

RuralMetropolitan

Program preparationTraining resources

Intervention ProtocolDocumentation

19

Aims

To implement and evaluate a Pharmacy Diabetes Care Program To identify and refer as appropriate people with undiagnosed diabetes; and To support the continuity of care for people with diabetes To improve the health of people with diabetes

H0: There will be no significant difference between intervention and control groups pre- and post intervention in:

• mean HbA1c, blood glucose levels, BP, TC and medication adherence • mean Quality of Life, well being scores • cost per life year /QALY saved

30 Intervention Pharmacies

Diabetes Medication Assistance Service

30 Control Pharmacies

No Service

Adherence assessment

Checks of medication history

Medication review

Meter downloads

Self care information

Checks for long term complications

Lifestyle information

PCDP Study Design

> 400 patients agreed to participate

> 65 ineligible

335 patients enrolled

159 Control Baseline Visit

140 Control Final Visit (6 mos)

18 withdrew 1 death

176 Intervention Baseline Visit

171 Intervention Visit 1 (2 wks)

163 Intervention Visit 2 (1.5 mos)

153 Intervention Visit 3 (3.5 mos)

149 Intervention Final Visit (6 mos)

5 withdrew

8 withdrew

10 withdrew

4 withdrew

Flowchart of DMAS recruitment and completion

Krass et al, Diabetic Medicine 2007; 24:677-683.

Change in HbA1c over time

23

8.08.3

7.9

8.9

7.07.5

8.08.59.0

9.510.0

baseline final

Mean

HbA

1C (%

)

Control (n = 107) Intervention (n = 125)

Intervention Δ HbA1c -1.03% (95%CI -0.8, -1.14)

Control Δ HbA1c -0.27% (95% CI: -0.15, - 0.39)

Krass et al, Diabetic Medicine 2007; 24:677-683.

Economic Outcomes

›Incremental cost over 5 years (discounted) = $3,373

›Cost per incremental life year saved = $24,029.

›PBAC funds interventions well above this amount.

›Likely to be cost effective

Conclusions The DMAS was effective at improving diabetes control as measured by

blood glucose levels and HbA1C.

The service increased patients understanding of long-term management of

their diabetes and improved their adherence to medications.

Both pharmacists and patients identified several benefits of the service and

expressed great satisfaction with the service.

DMAS is likely to be cost-effective when compared with many interventions

that currently funded (e.g. drugs listed on the PBS)

Pharmacy based interventions provide a way of improving health outcomes

and promote more efficient use of existing medicines.

Asthma Management Services

Saini B “Development, Implementation and Evaluation of a Pharmacy Based Asthma Care Model” [PhD Thesis] supervised by Prof C Armour & Ass Prof I Krass

Bosnic-Anticevich S, Saini B, Smith L, Krass I, Armour C “Asthma Self-Management in the Community” [Report] Investigator-initiated grant through 3rd Agreement R&D program

National Implementation: Armour C, Saini B, Bosnic-Anticevich S, Smith L, Krass I, Stewart K, Burton D, Emmerton L “Asthma Pilot Program: Stage 1 Implementation” as part of professional programs and services in the 4th Community Pharmacy Agreement (2005-2010)

2004- 2006

Armour C, Saini B, Bosnic-Anticevich S, Krass I, Taylor S “Innovative Management Scheme: Managing Asthma in Rural Community” [Report] Investigator-initiated grant through 3rd Agreement R&D program

2002- 2003

2004- 2005

Armour C, Saini B, Bosnic-Anticevich S, Krass I, Smith L, Stewart K, Emmerton L, Burton D, Simpson M, Lough S “Pharmacy Asthma Care Program” [Report] Commissioned study through 3rd Agreement R&D program

2008- 2009

2001- 2003

The Asthma DSM Service Six step plan followed

Spirometry at each visit

Medication issues/SEs/asthma control

Inhaler technique

Adherence assessment and Health Beliefs

Identify triggers

Action plan ownership and understanding

Goal setting

PACP recruitment and completion

396 Patients Recruited

Visit 2 166

Control Intervention (PACP)

Baseline Visit 205

19 did not complete

Final Visit 186(90.7%)

Baseline Visit 191

Final Visit 165(86.4%)

15 withdrew

11 more did not complete

Visit 3 44

Optional

Asthma severity (control) status Comparison of control and intervention groups

**

**

**

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Baseline Final Baseline Final

Per

cent

age

Mild

Moderate

Severe

CONTROL INTERVENTION

Armour et al., Thorax 2007 62: 496-502.

Economic Outcome

› Incremental cost over 5 years (discounted) = $590

›Cost per QALY = $2,946 ›PBAC funds interventions well above this amount.

›Cost effective

Gordois et al, Disease Management and Health Outcomes , 2007;15:387-96.

Question?

Can the DMAS or PACP, programs which

has been shown to have clinical and cost effectiveness in a small sample of

pharmacies be effectively translated into broader community practice?

31

Diabetes Pilot Program

Stage 1 DMAS Implementation Trial was to test: - Implementation feasibility - The effectiveness of a 6 month DMAS service versus a 12 DMAS month service

- The sustainability of improvements after the service has been completed

Stage 2 – DMAS implementation in 800 community pharmacies across Australia

32

33

Patient Recruitment

For a patient to be involved in Stage 1 DMAS as part of the Pilot Program, they must:

› have established type 2 diabetes with HbA1c > 7.0% confirmed by test results (within the previous 6 months) from the patient’s GP

› be a regular prescription customer of the pharmacy for at least the previous 3 months in order to generate a meaningful medication history

During Stage 1 - limit of 10 eligible patients per pharmacy

to receive a subsidised DMAS.

34

Training

›Module 1 (pre-reading) of the training manual (an electronic version) sent 2-3 weeks before training workshop

›The workshops comprised a mix of lectures, skills sessions, case discussions and role plays

›Each 2 day training workshop attended by 7-14 pharmacists

35

Credentialing

› Administered by AACP › 3 components:

1. MCQ test based on manual material (end of DAY 1) 2. Assessment of skills in demonstrating the blood

glucose monitor and using the Precision Link software.

3. Case studies on interpretation of blood glucose data (end of DAY 2)

36

Monitoring the implementation process

› Pharmacists - telephone surveys

- focus groups

› Pharmacy Audits › Patients

- telephone surveys

› GPs - telephone surveys

Overall experience –barriers and facilitators

Feedback from customers

Interaction with GPs and Diabetes educators

Impact on business and relationships

Involvement in future DMAS delivery

Overall experience of DMAS

Benefits

Satisfaction with service delivery

Demand/Willingness to pay

Awareness/experience of DMAS

Perceptions of impacts

Communication with pharmacists

Need for DMAS

Compliance with eligibility criteria

Program protocols

Study Design

38

Group 1 6 months

Visit 0 Baseline

Data

Visits 1,2 4 months,

6 month final visit Data

12 months Data

18 months Follow up

data

Group 2 12 months

Visit 0 Baseline

Data

Visits 1,2 4 months,

6 months visit Data

9 months visit

12 months visit Data

18 months Follow up

data

BGL

HbA1c, BP,

Lipids QoL

HbA1c BP

Lipids eGFR QoL

BGL

HbA1c, BP,

Lipids QoL

HbA1c BP

Lipids eGFR QoL

Consumer satisfaction

Consumer satisfaction

RESULTS

DPP Stage 1 Implementation

Results

Key Barriers to DMAS Implementation

Resistance from local GPs and diabetes educators

Insufficient numbers of eligible patients

Lack of staff to facilitate organisation of appointments

Patients not keeping appointments

Shortage of pharmacists to allow for uninterrupted DMAS

Excessive time taken to deliver service

Insufficient pharmacist remuneration for the DMAS

Over commitment of pharmacy to multiple professional

services

Flowchart of DMAS recruitment and completion

41

998 patients agreed to participate

474 INELIGIBLE

524 patients enrolled

260 Group 1

Visit 0

264 Group 2

Visit 0

254 Group 1

Visit 1

249 Group 2

Visit 1

237 Group 2

Visit 2 232 Group 2

Visit 3

220 Group 2

Visit 4

202 Group 2

Visit 5

241 Group 1

Visit 2 221 Group 1

Visit 3

15 withdrew

12 withdrew

5 withdrew

12 withdrew

18 withdrew

18 withdrew

6 withdrew

13 withdrew

19 withdrew

19 withdrew

184 Group 2

Visit 6

203 Group 1

Visit 4

Changes in BGL (mmol/L) during DMAS

42

Proportion of patients at clinical targets for optimum diabetes management

43

Group 1 Group 2

Sustainability: HbA1c by group by time

44

EQ 5D – Changes in Utility Scores

45

0.5

0.55

0.6

0.65

0.7

0.75

0.8

0.85

Baseline: EQ-5D score Completion: EQ-5D score 18 month: EQ-5D score

EQ-5

D s

core

Time Points

Group 1 (n=117)

Group 2 (n=104)

› Increase in their knowledge of diabetes

and its complications

› Pharmacist gave them education on lifestyle issues which resulted in improvements in lifestyle and quality of life

› Patients reported improvements in their understanding of diabetes medications

› Patients thought the most useful part of DMAS was the printouts of their blood glucose results

› Patients reported that the DMAS led to improved monitoring of their diabetes

46

“I have learnt about diet and exercise and to keep going at it. I have seen the benefits already” (Patient 19, TAS)

“Diabetes can damage your eyes and heart....all those things” (Patient 14, WA)

“Having it explained on the printouts was great. Even the doctor was impressed” (Patient 11, VIC)

“I learnt a lot about my medications…. as was having side effects” (Patient 12, WA)

“ It gave the opportunity for closer monitoring of my diabetes and more focus on lifestyle such as increased exercise ” (Patient 22, NSW)

Conclusion

The DMAS may be successfully implemented into diverse community pharmacy settings providing 1. the pharmacy has adequate staff, remuneration and

infrastructure to support service provision; 2. there are good pharmacist-GP relationships; 3. the pharmacy has a pool of eligible patients; and 4. there is effective promotion and integration of the DMAS

within the healthcare sector.

47

FEASIBILITY

Conclusion

› The DMAS resulted in significant health benefits for people with Type 2 diabetes. - Significant improvements in glycaemic control - Reduction in other CVD risk factors - The clinical effectiveness of DMAS was independent of the duration (6

month vs.12 month DMAS) or intensity (5 visits vs. 7 visits) of the service - Based on evidence from large clinical trials 1-3, the extent of improvement in

diabetes control achieved by the DMAS will translate into future cost savings to the health care system in delaying and reducing diabetes related complications.

1. UK Prospective Diabetes Study (UKPDS) Group). Lancet. 1998, 352: 837–853

2. Diabetes Control and Complications Trial Research Group. New England Journal of Medicine. 1993, 329: 977–986

3. Stratton I.M., Adler A.I., Neil H.W. et al. British Medical Journal, 2000; 321: 405-412

48

HEALTH OUTCOMES

Conclusion

› Overwhelmingly, the DMAS service was well received and highly valued by patients

› The most useful aspect of the DMAS was the pharmacists’ support of blood glucose monitoring as a tool to help the patient to effectively self-manage aspects of their diabetes.

› The visit to the pharmacist was worth about the same as a visit to the GP

› Their willingness to pay was based on whether they were currently bulk-billed and the gap they paid over and above the Medicare rebate.

49

DPP Stage 2

› DMAS was rolled out to 800 pharmacies around Australia

› The number of active pharmacists (with 1 or more patients) in the program was 251. This represented 32% of the 785 pharmacists trained and credentialed.

› Only 11% of the potential pool of 5,495 participants (785 pharmacists with 7 patients in the evaluation sample).

› An average of 2.4 patients for every active pharmacist (n=251) in the program.

› A total of approximately 1,000-1,250 patients participated in the DMAS 2 nationally

The program evaluation highlighted several significant barriers to broad implementation.

50

PHARMACY ASTHMA MANAGEMENT SERVICE (PAMS)

• Evidence from RCT • Cost Effective • Implementation trial (Broad Scale) • Sustainability • 3 versus 4 visits over 6 months • Barriers and Facilitators • Business Model • 3 states and 1 territory • WHY IS THIS IMPORTANT ? NOT RCT

PARTICIPANTS

PAMS Baseline vs Final › Asthma Control

0

10

20

30

40

50

60

70

80

90

100

3 visit Baseline 3 visit Final Visit

4 visit Baseline 4 visit Final Visit

Prop

ortio

n of

pat

ient

s (%

)

Time points

Poor

Fair

Good

Key Findings of PAMS implementation trial

› 3 visits over 6 months produced similar clinical and humanistic outcomes to 4 visits

› Visits spaced at baseline, one month later and 6 months › Improvements sustained at 6 months and (inhaler technique)

at 12 months also. › Patients and practitioners liked the service (liked the

spirometry) › Suggest a 3 visit service followed up by 12 month review with

occasional checking for some patients at 6 months would be sufficient to improve and maintain asthma control in most individuals.

DOCUMENT

China National Essential Drug Administration, Policy and Practices Program, Sydney December 2011

Int J Clin Pharm (2012) 34:43–52

Validation of the DOCUMENT

12 week trial 185 community pharmacies 2,1023,923 prescriptions 5,948 DRPs CI rate 0.3% 1.6 IV per prescription Recommendations

- change in therapy (40.1%) - provision of information (34.7%).

› Clinical significance - 13.9% - high - 32% - moderate

Williams M et al Int J Clin Pharm (2012) 34:43–52

Professional Programs in the 5CPA

Pharmacy Practice Incentives (PPI) - $344M

Medication Management

Medicines Use Reviews (Medscheck) - $29.6M

Diabetes Medication Management Service (Diabetes Medscheck) - $12.2M

Home Medicines Reviews (HMR) - $52.11M

Residential Medication Management Reviews (RMMR) - $70M

April 2013

Uptake of MedsCheck/Diabetes MedsCheck

›3,232 pharmacies participating in our GuildCare 5CPA programs

›1 July 2011 up until the end of February 2013

›34,000 were MedsCheck/Diabetes MedsCheck delivered by 1300 pharmacies.

PPI programs

Providing incentives to accredited pharmacies for the:

demonstrated delivery of agreed quality services to patients that are designed to improve their quality use of medicines demonstrated achievement of defined outcomes in

relation to the delivery of quality services to patients

April 2013

Pharmacy Practice Incentive (PPI) Program

Pharmacy Practice Incentive (PPI) Program

Dose Administration Aids (DAAs)

To assist consumers in the community to better manage their medicines, with the objective of avoiding medication misadventure and associated

hospitalisation.

$132 million over the life of the Agreement (5

years)

Apr

Pharmacy Practice Incentive (PPI) Program

Australian Department of Health and Ageing Evaluation of the DAA/PMP Programs June 2010 – 4CPA http://www.health.gov.au/internet/main/publishing.nsf/Content/5B1B138DA00BB9C7CA2578150083984E/$File/DAA%20PMP%20Report.pdf

Clinical Interventions

$97 million over the life of the Agreement (5 years)

Pharmacy Practice Incentive (PPI) Program

A clinical intervention: ‘any professional activity by the pharmacist directed towards improving the quality use of medicines and resulting in a recommendation for a change in the patient’s medication therapy, means of administration or medication-taking behavior.’

Incentive Payments Eligible Community Pharmacies will be paid 4 times per year for meeting the PPI and QCPP requirements when delivering a DAA and a clinical intervention service.

Payments are calculated based on a complex formula for each claiming period that considers: the available funding pool for that period;

no. of pharmacies claiming for that period;

service volume (e.g., no. of DAA patients serviced in that period or clinical interventions delivered in that period ); and

claimable prescription volume for that period.

April 2013

Staged Supply

April 2013

Pharmacy Practice Incentive (PPI) Program

$35 million over the life of the Agreement (5 years) An incentive payment of approx. $1000 annually

Supply medicines to consumers in periodic installments of less than the total required or prescribed quantity at agreed intervals.

Mental illness; Drug dependency; or Who are otherwise unable to manage their medicines safely

Primary Health Care

April 2013

$75 million (Primary Health Care, Community Services Support and Working with Others) over the life of the Agreement (5 years)

Pharmacy Practice Incentive (PPI) Program

An incentive payment of approx. $850 will be paid annually

Requirements

Elements Screening/Risk Assessment Service

Disease State Management Service

1. Diabetes 2. Respiratory Disease 3. Cardiovascular

Disease

4. Mental Health Conditions

5. Health Promotion Service

Eligible Community Pharmacies participating in this priority area must provide at least three services across more that one element in accordance with Program requirements.

April 2013

April 2013

What does this mean? Eligible Community Pharmacies are required to have provided at least three services in accordance with the PPI Program Specific Guidelines (November 2012).

NOTE: Screening/Risk Assessment services and Disease State Management services can be delivered for the same disease state (element) and will be counted as two services

For example: 1. Health Promotion (e.g. Know your numbers, Show us your lungs, diabetes awareness etc.)

AND 2. Screening/Risk assessment service under

Cardiovascular disease AND

3. Disease State Management service under Cardiovascular disease

1. Needle and syringe programs

2. Opioid Substitution programs

3. Return of Unwanted Medicines (RUM)

4. Staff training (Including Cert III & IV)

5. e-Health

6. NDSS Access Point

7. Pharmacy Delivery Service

8. Mental Health First Aid Training

April 2013

Community Services Support Eight elements focused on medicine safety, harm minimisation and services to support the community.

• Staff training requirements

• An incentive payment of approx. $850 will be paid annually

Working with Others Service areas where inter-professional collaboration

might occur include: MedsCheck /Diabetes MedsCheck Dose Administration Aids Clinical Interventions Supplying Pharmacy Medicines and Pharmacy

Only medicines Disease State Management to improve Quality

use of Medicines (QUM) Home Medicine Review Medication Adherence Smoking Cessation Other professional Services including conditions

such as diabetes, respiratory disease, cardiovascular disease or mental health conditions.

April 2013

$850 annually for meeting PPI Program requirements when recording specific cases of inter-professional collaboration with at least three non-pharmacy health professional groups

Concluding comments

› PHARMACY PRACTICE RESEARCH IS critical to development of the profession

› In the Australian context it has influenced government policy

› Challenges in translation - The infrastructure of pharmacy

- Slow rate of diffusion of practice change

- Pharmacists attitudes

- Resource limitations

- Resistance to boundary encroachment

- Underdeveloped relationships with other HCPs

Concluding comments

Drivers for change - Need for new sources of income

- Shrinking income from dispensing -

- transparency in pricing from 'approved price to pharmacists' to 'approved ex-manufacturer price’

- recent report by Grattan Institute recommending a cap on the overall budget for the Pharmaceutical Benefits Scheme and drastically lower prices for generic drugs.

- Upsurge in discount pharmacies

- Aging of the population – rising needs for medication management services

Acknowledgements

72

The Department of Health and Ageing for funding these projects through the Third and Fourth Community Pharmacy Agreements

References

› Smith L et al. A Self-Management Model of Illness Behaviour Aids the Treatment of Asthma in an Australian Community Pharmacy Setting. Soc Sci & Med 2007;64:1501-11

› CL Armour et al. Pharmacists leading the way in diabetes care – disease state management JAPhA 2004, 44:455-466

› Krass I et al. Pharmacists leading the way in diabetes care – the impact on medication use and adherence JAPhA 2005; 45(1): 35-40

› I Krass, et al. The Pharmacy Diabetes Care Program: Evaluating the impact of a diabetes service model delivered by community pharmacists in Australia Diabetic Medicine 2007; 24:677-683

› Armour C et al. Pharmacy Asthma Care Program (PACP) improves outcomes for patients in the community, Thorax 2007 62: 496-502

› Adam Gordois, et al "Cost-effectiveness analysis of a pharmacy asthma care program in Australia Disease Management and Health Outcomes , 2007;15:387-96

› Krass I, et al. Diabetes Medication Assistance Service (DMAS) Stage 1: Impact and Sustainability of Glycaemic and Lipids Control in Patients with Type 2 Diabetes. Diab Med, 2011; 28: 987-93. doi: 10.1111/j.1464-5491.2011.03296.

› Saini B et al. Role of community pharmacists in asthma – Australian research highlighting pathways for future primary care models. Australasian Medical Journal. 2011;4:190-200.

› Saini B et al. Asthma disease management – Australian pharmacists’ interventions improve patients’ asthma knowledge and this is sustained. Patient Educ Couns 2011;83:295-302. [2 citations].

› Mitchell B, et al. Diabetes Medication Assistance Service: The Pharmacist's Role in Supporting Patient Self-Management of Type 2 Diabetes (T2DM) Patient Educ Couns 2011;83:288-94. [ 1 citation]

› Emmerton LM et al. Experiences of pharmacists involved in the delivery of a specialist asthma service in Australia. BMC Health Services Research (Impact factor 1.72, ERA rank B). 2012. doi: 10.1186/1472-6963-12-164.PMID:22709371

› Armour CL et al. Feasibility and effectiveness of an evidence-based asthma service in Australian community pharmacies: a pragmatic cluster randomised trial J Asthma. 2013; 50(3): 302-9.

› Smith LD et al The contribution of goal specificity to goal achievement in collaborative goal-setting for the management of asthma. Res Soc Admin Pharm doi:pii: S1551-7411(13)00019-3. 10.1016/j.sapharm.2013.02.002. [Epub ahead of print] PMID:23545118.

› Research and Development. Pharmacy Guild of Australia available at http://www.guild.org.au/The_Guild/tab-Pharmacy_Services_and_Programs/Research_and_Development/Research

Please direct your questions regarding CEUs to Phil Emberley, Director of Pharmacy Innovation, CPhA, pemberley@pharmacists.ca.

Continuing Education Form

CPhA National Conference 2013 June 1 – 4, 2013, Charlottetown, PE

The Canadian Council on Continuing Education in Pharmacy has approved CPhA as an Accredited Provider of continuing education. The conference has been accredited under program number 8002-2013-115-C-P for a total of 12.75 CEUs.

PLEASE NOTE: • Sessions indicated by an asterisk (*) are sponsored. These sessions are not accredited under the conference

program number. The sponsor will provide accreditation information at the session. • Pre-conference workshops are not accredited under the conference program number, nor listed on this

form. Participants will receive their Statement of Participation at the workshop(s).

Delegates are encouraged to use this form to track their learning. For delegates who must submit CEUs to their licensing body, please make a copy of this form for your files and submit the original to your provincial licensing body.

Name: __________________________________________________________________________________________

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SUNDAY, JUNE 2, 2013

Time Session Speaker/Sponsor CEUs 7:00 am-8:30 am CE Satellite Breakfast Presentation* 1.0*

11:45 am-1:00 pm Luncheon Presentation – Learn How to Interpret Your Financials

Teva Canada 0.75*

1:15 pm-2:00 pm Balancing Risk & Benefits of Hormone Therapy for Menopause

Anne-Marie Whelan 0.75

1:15 pm-2:45 pm Pharmacy Practice Research – Oral Presentations Oral Abstract Presenters 1.5 1:15 pm-2:45 pm Canada’s Drug Review Processes Brian O’Rourke 1.5 2:00 pm-2:45 pm The Link Between the Heart and the Kidneys Marisa Battistella 0.75 3:00 pm-4:30 pm Pharmacy Practice Research – Oral Presentations Oral Abstract Presenters 1.5 3:00 pm-4:30 pm Improve Productivity in Community Pharmacy through

Workflow and Design Wayne Caverly 1.5

3:00 pm-4:30 pm Pharmacy Practice 3.0 – Putting Prescribing in Perspective

Matt Tachuk 1.5

Maximum daily CEUs under conference accreditation: 3.00 *Maximum daily CEUs from sponsored CE sessions: 1.75

Please direct your questions regarding CEUs to Phil Emberley, Director of Pharmacy Innovation, CPhA, pemberley@pharmacists.ca.

MONDAY, JUNE 3, 2013

Time Session Speaker/Sponsor CEUs 7:00 am-8:30 am CE Satellite Breakfast Presentation* Disease

Interrupted: Tobacco Reduction & Cessation Charl Els, Jane Ling LifeScan Canada

1.0*

8:30 am-9:30 am New Oral Anticoagulant Therapy: Is Newer Better? Bill Semchuk 1.0 8:30 am-9:30 am e-Health: A Cross Country Check-Up Justin Bates 1.0 8:30 am-9:30 am CPJ Session – Translating Research Evidence into

Australian Pharmacy Practice: Successes & Challenges Ines Krass 1.0

10:00 am-12:00 pm Pharmacy Practice Innovation Showcase Bareham, Barnes, Gray, Jorgenson, Sadowski, Taylor

2.0

2:30 pm-3:30 pm Looking Back, Looking Forward: The Public Policy Landscape in Pharmacy

Jeff Morrison 1.0

2:30 pm-4:30 pm Diabetes Mini Sessions (CANRISK, Diabetic Foot Care, 2013 CDA Guidelines)

Kerry Mansell, Rob Roscoe 2.0

3:30 pm-4:30 pm Debt Management for Pharmacy Students and New Practitioners

Michèle Seaton-Gascon 1.0

Maximum daily CEUs under conference accreditation: 5.00 *Maximum daily CEUs from sponsored CE sessions: 1.0 TUESDAY, JUNE 4, 2013

Time Session Speaker/Sponsor CEUs 7:00 am-8:30 am CE Satellite Breakfast Presentation* D-lemmas of

Vitamin D: Who Needs It and How Much? Stephanie Atkinson Kellogg Canada

1.0*

8:45 am- 9:45 am Managing Chronic Non-cancer Pain (CNCP): Finding Pearls & Avoiding Pitfalls

Loren Regier .75

8:45 am-10:15 am Pharmacy Practice Research – Oral Presentations Oral Abstract Presenters 1.5 8:45 am-10:15 am Connect and CARE: Engaging Patients Over-the-

Counter in Canada’s New Pharmacy Environment Lisa Guirguis, Sherrill Johnson

1.5

9:45 am-10:15 am Pharmacist’s Role in Shingles Vaccination Kathryn Slayter .75 10:30 am-11:15 am Parkinson’s Disease: Optimization of Medication

Management Janice Irvine-Meek .75

10:30 am-11:45 am Pharmacy Trends-A Time of Global Change Jeff Poston 1.25 11:15 am-11:45 am Managing Behavioural & Psychological Symptoms of

Dementia Susan Bowles .5

12:00 pm-1:30 pm Luncheon Presentation – from Pharmacist to Premier Hon. Darrell Pasloski (invited)

1.0

1:45 pm-2:45 pm The Multi-Generational Workplace David Foot 1.0 Maximum daily CEUs under conference accreditation: 4.75 *Maximum daily CEUs from sponsored CE sessions: 1.0