Improving the Outcomes of Oral Anticoagulation:

Home Monitoring of Warfarin Therapy

Jack Ansell, M.D.

Lenox Hill Hospital, NY

September 22, 2009

DisclosuresConsultant: Roche Diagnostics, ITC, HemoSense

The Dilemma of Anticoagulation Management

• Warfarin has a narrow therapeutic window of effectiveness and safety.

• Many factors influence a patient’s stabilitywithin that window.

• Frequent monitoring is required to maintainpatients in the therapeutic window.

• Monitoring is labor intensive and complex.

Consequences•Increased adverse events with poor management •Physicians avoid warfarin use because of its complexity.

ORAL ANTICOAGULATION IS ALL ABOUT MANAGEMENT

Risks1,2

Benefits2,3

Reduction in risk of stroke or venous thromboembolism (VTE)

Hemorrhage

INR

1. Ansell J et al. Chest. 2004;126:204S-233S. 2. Hirsh J et al. J Am Coll Cardiol. 2003;41:1633-1652.3. Rothberg MB et al. Ann Intern Med. 2005;143:241-250.

The Desired Outcome: Benefits must be greater than RisksHospital Transition to Outpatient Outpatient

4

Transition from Hospital to Ambulatory Care Settings

5

Treatment decisions involving inappropriate assessment of response

Total = 647 decisions

8%1%

10%

1%

1%

10%

69%

Initial dose too high (52 decisions)

Initial dose too low (9 decisions)

Different dose from home therapy (63 decisions)

Continued home dose but should have been changed (6 decisions)

Continued home dose but should have been held (4 decisions)

Held dose when therapy shouldhave been restarted (66 decisions)

PK/PD not taken into account (447 decisions)

• 349 records reviewed and assessed by established criteria• 647/2030 (31.8%) warfarin treatment decisions were deemed inappropriate

How well does a University Hospital do in managing warfarin therapy?

“Inpatient Warfarin Medication Utilization Evaluation”

6

35.3% (123/349) patients were initiated on warfarin in-house for the first time

New starts (n=123)

42%

7%

51%

Dose too high

Dose too low

Dose ok

Is the correct starting dose used?“Inpatient Warfarin Medication Utilization Evaluation”

7

New starts for VTE indication (n=47)

Initial Dose Inappropriate (n=23)

Initial Dose Appropriate (n=24)

Bleeding events 4 documented bleeds3 transfusions ≥ 2 u5 > 2 g/dL decr. Hgb

2 documented bleeds4 transfusions ≥ 2 u5 > 2 g/dL decr. Hgb

Bleeding risk distribution

15 high risk6 moderate2 low

11 high risk8 moderate5 low

Vitamin K use 4 pts 1 pt

What is the impact on outcomes?“Inpatient Warfarin Medication Utilization Evaluation”

Models of Chronic Anticoagulation Management

Routine Medical Care (Usual Care)AC managed by physician or office staff w/o any systematic program for education, follow-up, communication, and dose management. May use POC device or laboratory INR

Anticoagulation Clinic (ACC)AC managed by dedicated personnel (MD, RN or pharmacist) with systematic policies in place to manage and dose patients. May use POC device or laboratory INR

Patient Self-Testing (PST)Patient uses POC monitor to measure INR at home. Dose managed by UC or ACC

Patient Self-Management (PSM)Patient uses POC monitor to measure INR at home and manages own AC dose

Challenges With ConventionalLaboratory Testing

• Patient issues– Time for traveling to office or laboratory– Ability to travel – Need for venous access

• Labor-intensive and higher costs– Scheduling visits– Proper handling and delivery of sample– Documentation at several time points

• Potential for communication delays– Laboratory to contact provider with results– Provider to contact patient with dosage adjustments

Jacobson AK. In: Ansell JE, Oertel LB, Wittkowsky AK, eds. Managing Oral Anticoagulation Therapy. 2nd ed. St. Louis, Mo: Facts and Comparisons; 2003;45:1-6.

Technology Advances:Offers a new paradigm for monitoring since 1987

• Use of capillary whole blood1,2

– Allows fingerstick sampling2

– Appropriate for self-testing1

• Consistency of INR results1

• Portability1

– Can be done anywhere • Simplicity1

– Patient can easily perform test

1. Leaning KE, Ansell JE. J Thromb Thrombolysis. 1996;3:377-383. 2. Ansell JE. In: Ansell JE, Oertel LB, Wittkowsky AK, eds. Managing Oral Anticoagulation Therapy. 2nd ed. St. Louis, Mo: Facts and Comparisons; 2003;44:1-6.

What are the outcomes with Home Monitoring?

Thromboembolism with PST or PSM vs Control

Heneghan et al. Lancet 2006;367:404

psm

pst

What is the

control group

Thromboembolism with PST or PSM

Heneghan et al. Lancet 2006;367:404

Usual Care

AMS

PSM

PST

Major Hemorrhage with PST and PSM vs Control

Heneghan et al. Lancet 2006;367:404

AuthorYear

Inter-vention

# Patients

TTR(% or time in range)

Major Hemorrhage

Thrombo-embolism

PST vs UCBeyth2000

PST/ams* vs UC 163 vs 162 56 vs 32 p<0.001 5.6% vs 12% p=0.049 8.6 % vs 13% p = 0.2

PST vs AMSWhite1989

PST/ams* vs AMS 23 vs 24 93 vs 75 p=0.003 0 0

Kaatz2001

PST/ams* vs AMS 63 vs 65 p=NSGadisseur

2003PST/ams* vs AMS 52 vs 60 63.9 vs 61.3 p=0.14 0 vs 1 event 0

THINRS2009

PST /ams vs AMS ~68% vs 63% p = NS

PSM vs UCHorstkotte

1998PSM vs UC 75 vs 75 92.4 vs 58.8

Sawicki 1999

PSM vs UC 83 vs 82 57 vs 33.8 p=0.006 1 event vs 1 event 1 event vs 2 events

Fitzmaurice 2002

PSM vs UC 23 vs 26 74 vs 77 p=NS 0 vs 1 event 0

Kortke2001

PSM vs UC 305 vs 295 78.3 vs 60.5 p=<0.001 1.7 % vs 2.6% p=NS 1.2% vs 2.1% p=NS

Sidhu 2001

PSM vs UC 34 vs 48 76.5 vs 63.8 p<0.0001 1 event vs 0 1 event vs 0

Sunderji 2004

PSM vs UC 69 vs 70 71.8 vs 63.2Voller 2005

PSM vs UC 101 vs 101 67.8 vs 58.5 p=0.0061 2 events vs 0 0 vs 1 event

PSM vs AMSWatzke

2000PSM vs AMS 49 vs 53 84.5 vs 73.8 1 event vs 0 1 event vs 0

Gadisseur 2003

PSM vs AMS 47 vs 52 66.3 vs 63.9 p=0.14 1 event vs 1 event 0

Khan 2004

PSM vs AMS 40 vs 39 71.1 vs 70.4Menendez-

Jandula 2005PSM vs AMS 368 vs 369 58.6 vs 55.6 p=NS 4 events vs 7 events 4 events vs 20 events

Improving AC Outcomes at the Time of Discharge

Discharge Day 8Home

MonitoringUC

MonitoringHome

MonitoringUC

Monitoringp

valueSub-therapeutic 49% 47% 29% 33%Therapeutic 42% 45% 67% 41% <0.01Supra-therap 9% 8% 4% 26%

Home Monitoring (n=59) Usual Care Monitoring (n=68)

Major Bleeding 2 10 0.05Total Bleeding 15 36 0.009Embolic Event 9 10 NSReadmit due to AC Complication 3 8 0.32Death 7 8 NS

Jackson et al. J Intern Med 2004:256:137

128 patients randomized to home POC monitoring (n= 60) or UC (n=68) after discharge. POC testing on d 2,4,6,8 vs UC on d 8

Adverse events up to day 90Adverse events up to day 90

Who is able to perform Home Monitoring?

Willing to:Learn and perform testing procedureKeep accurate written recordsCommunicate results in timely fashion

Able to:Participate in a training program to acquire skills/competencies to perform self-testingGenerate an INRUnderstand implications of test resultMaintain records

Reliable to:Perform procedure with acceptable technique to obtain accurate results

Considerations for Patient Selection

The THINRS Trial: Design

• Purpose: Compare HQACM with PST to HQACM alone on majorhealth outcomes

• Patient population: Atrial fibrillation or mechanical heart valve

• Participating Centers28 VA Med Ctrs with ACC of > 100 patients

• Two parts:Part 1: Training and home testing for 2-4 weeksPart 2: Competency assessment and, if capable,

randomization to HQACM every 4 weeks or PST every week

Matchar. Amer J Med 2002;113:42-51

= ACC

A key attribute of this trial is that “everyone” was trained for PST and those who were deemed capable, then randomized to either PST or ACC management

The THINRS Trial: Design

Matchar. Amer J Med 2002;113:42-51

Interventions:• HQACM (monthly INR)

Designated, trained staff personLocal standard management algorithm

• PST (Weekly INR)Interactive value response reporting system with web-based local monitoring

Outcomes:• Primary

time to first major event (stroke, major bleed, death)• Secondary

time in range, satisfaction, quality of life

The THINRS Trial: Intervention & Outcomes

Matchar. Amer J Med 2002;113:42-51

Anticoag Clinic

Dose management

Anticoag Clinic

Dose management

3,644 Trained

3,566 home with meter for 2-4 weeks

3,058 competency assessment

2,922 randomized

78 did not pass training

508 dropped out

136 did not pass assessment or dropout

2,922 / 3,644 = 80% Passed Competency

The THINRS Trial: Participants

Matchar. Amer J Med 2002;113:42-51

Summary from THINRS: Outcomes

• 80% of screened subjects demonstrated PST competency and were randomized – approx. 4 out of 5 pass

• Patients were less likely to pass PST, if– Older, h/o CVA, poor cognition, low literacy,

poor manual dexterity

Matchar. Amer J Med 2002;113:42-51

Summary from THINRS: Outcomes: Stroke, Bleed, Death

EventType

4,235 pt yrs

HQACM

Rate per pt-yr

4,495 pt yrs

PST

Rate per pt-yr Total

Rate per pt-yr

Stroke 32 0.76% 31 0.69% 63 0.72%

MajorBleed

189 4.46% 173 3.85% 362 4.15%

Death 157 3.71% 152 3.38% 309 3.54%

Total 378 8.93% 356 7.92% 734 8.41%

HQDM PST

Summary from THINRS

• 80% of screened subjects demonstrated PST competency and were randomized – approx. 4 out of 5 pass

• Patients were less likely to pass PST, if– Older, h/o CVA, poor cognition, low literacy,

poor manual dexterity

• Outcomes (TTR & AEs) were improved to a small degree with PST

How Does Home Monitoring Achieve Good Outcomes ?

• Access to testingFrequency (convenience), timeliness

Greater Time-in-Range

• Consistency of testingInstrument & thromboplastin

Consistent Results

• Awareness of test resultsKnowledge, empowerment, compliance

Greater Time-in-Range

Managing Home Monitoring?

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

INR

by

left

hand

fing

erst

ick

1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

INR by right hand fingerstick

FS LT INR = .258 + .89 * FS RT INR; R^2 = .956

Trusting the INR Result

Trusting the INR ResultThromboplastin — Reagent Combinations and observed variation in INR

1.5

2

2.5

3

3.5

4

4.5

5

5.5

Ortho 1.00 BFA

DADE 1.03 BFA

Behring 1.08 BFA

Pacific Hem 1.20 BFA

IL Test 1.43 BFA

DADE 1.96 BFA

Ortho 1.00 ACL

DADE 1.03 ACL

Behring 1.08 ACL

Pacific Hem 1.20 ACL

IL Test 1.43 ACL

DADE 1.96 ACL

Ortho 1.00 MLA

DADE 1.03 MLA

Behring 1.08 MLA

Pacific Hem 1.20 MLA

IL Test 1.43 MLA

DADE 1.96 MLA

Courtesy A. Jacobson

0

10

20

30

40

50

60

70

80

90

100

0 7 14 21 28 35 42 49

% i

n R

ang

e

Days Between TestsSummary 18 published studies: PST Coalition Report, July 2000

More Frequent testing increases % in range

Optimal Frequency of INR Monitoring*Test Interval vs % In Range

1. Jacobson AK. In: Ansell JE, Oertel LB, Wittkowsky AK, eds. Managing Oral Anticoagulation Therapy. 2nd ed. St. Louis, Mo: Facts and Comparisons; 2003;45:1-6. 2. Roche Diagnostics. CoaguChek System: Why Use? Available at: http://www.coaguchek-usa.com/information_for_professionals/why_use/content.html. Accessed May 12, 2006. 3. Wittkowsky AK et al. Pharmacotherapy. 2005;25:265-269.

Barriers to PST/PSM

• Lack of physician awareness or acceptance1,2

• Fear it will lead to unintended self-management3

• Implementation of PST/PSM3

• Reimbursement3

Barriers to INR Patient Self-Testing (PST): National Survey of Anticoagulation Practitioners1

Cost of Device Main Barrier

1. Wittkowsky AK et al. Pharmacotherapy. 2005;25:265-269.

60.4

78.7

35.7

0

10

20

30

40

50

60

70

80

90

Cost of device Cost ofreagent

cartridges

Fear of PSTleading to PSM

Provider Barriers to PST

Survey Respondents

(%)

Willingness to Pay for PST is low

• Few patients are willing to pay for self-testing, despite the benefits of weekly testing.

• Those willing to pay for PST stated an average of $18 per month as the acceptable out-of-pocket expense for home testing with a POC device.

Amount Willing to Pay Out-of-Pocket Per Month

Percent Respondents

n=71

$0 35%

$5 - $30 51%

$35 - $100 14%

Proprietary information

CMS did the right thing by approving reimbursement, but they did it the wrong way

As of March 19, 2008 CMS expanded coverage

to patients with VTE and chronic AF

Medicare National Coverage Policy for Home PT/INR Testing (as of July 2008)

Medicare will cover the use of home INR monitoring for chronic, oral anticoagulation management for patients with mechanical heart valves (non-porcine), chronic atrial fibrillation, or venous thromboembolism . The monitor and the home testing must be prescribed by a treating physician and all of the following must be met:

• Patient anticoagulated for at least 3 months• Patient must undergo face-to-face educations program and

demonstrate correct use of device• Patient continues to correctly use device• Self-testing no more frequently than once per week

More information at:http://www.cms.hhs.gov/MLNMattersArticles/downloads/MM6313.pdf

Oral Anticoagulation Patient Self-Testing: Consensus Guidelines for Practical Implementation. Managed Care 2008;17(#10, Suppl 9):1-9

What is an IDTF ?

CMS defined a new entity independent of a hospital or

physician’s office in which diagnostic tests are

performed by licensed or certified non-physician

personnel under appropriate physician supervision.

This entity is called an Independent Diagnostic Testing

Facility (IDTF). The IDTF may be a fixed location, a

mobile entity, or an individual non-physician practitioner

and in all cases must comply with the applicable laws

of any state in which it operates.

IDTF’s… How They Work

Doctor

Patient CMS

Device Manufacturer

IDTF

Manages

INR

INR

INR

Instorder

Instsent

Rx

InstteachTech fee

$140/monServ + Inst

Prof fee$9/mon

Train fee$191

Oral Anticoagulation Patient Self-Testing: Consensus Guidelines for Practical Implementation. Managed Care 2008;17(#10, Suppl 9):1-9

Communication with patient doing home monitoring

PST dosed by internet expert system vs AMS

Criteria AMS Supervised PST P - value

# INRs /pt (mean) 10.7 (+ 5.2) 41.7 (+ 6.6) <0.001

Freq of testing (mean) 19.6 days 4.6 days <0.001

Time in range 58.6% 74% <0.001

Extreme INRs 6 % 1.7 % <0.001

INRs < 1.5 45.9 % 33.3 % <0.001

INRs > 5.0 (%) 54.1 % 66.7 % 0.006

RCT (cross-over) of 162 patients, followed for 6 months; mean age 59 yr (16-91), 80% male with diverse indications.Daily time to manage 80 patients 10-45 min (mean 23.2 min)

Ryan et al. J Thromb Haemost 2009;7:1284

• Anticoagulants (oral and parenteral) top the list for adverse events.• Management of warfarin therapy is often poor, even in the best of

circumstances.• The transition from inpatient to outpatient anticoagulation is a critical transition

that requires labor intensive systems and processes for successful implementation.

• POC INR technology can play an important role in facilitating such care.• Anticoagulation management models include Routine or Usual Care,

Anticoagulation Clinics, and PST/PSM (home monitoring)• Point-of-care (POC) provides an alternative to laboratory testing that is easy,

portable, and accurate and allows for testing either by physician or patient• POC home monitoring can be done either with physician management or

patient self-management• Home monitoring requires systems in place to implement and manage results.

IDTFs can perform much of the implementation and follow up tracking of results

Conclusions . . .