CURE, HARM and GIMCURE, HARM and GIMAcademic ½ DayAcademic ½ DayOctober 24October 24thth 2001 2001

Dr Hui N. Lee, MD, M.Sc., FRCPC

Community GIM, Sault Ste Marie

Clinical Assistant Professor McMaster University

ObjectivesObjectives

Practical knowledge of current ACS management (October 2001)

Overview of CURE study and role of clopidrogel in ACS therapy

Principles of evaluation of HarmUnderstanding of Community GIM roleInvitation for electives Up North

ScenarioScenario

67 year old man, non-Q MI with troponin I 8.2 / CK 300– Diabetes, HTN, dyslipidemia, ex-smoker– No previous MI or CAD, but GI bleed– Was on ASA, other standard meds

Now 3 days post MI– Rx ASA, clopidrogel, stop enoxaparin, other

Rx standard

Non-ST Elevation ACSNon-ST Elevation ACS

When do you add Clopidogrel? When do you stop Clopidogrel? How do you place Clopidogrel in relation to other

expensive/potentially risky interventions:– angiogram– LMW heparin– IV G2b3 inhibitors

Do you put Clopidogrel on formulary

CURECURE (OASIS-4)CURE (OASIS-4)

Clopidogrel in Unstable Angina to prevent

Recurrent ischemic Events

Atherothrombosis: a Generalized Atherothrombosis: a Generalized and Progressive Processand Progressive Process

NormalNormalFattyFattystreakstreak

FibrousFibrousplaqueplaque

Athero-Athero-scleroticscleroticplaqueplaque

PlaquePlaquerupture/rupture/fissure &fissure &

thrombosisthrombosis MIMI

IschemicIschemicstroke/TIA stroke/TIA

Critical leg Critical leg ischemiaischemia

Clinically silentClinically silent

CardiovascularCardiovasculardeathdeath

Increasing ageIncreasing age

Stable anginaStable anginaIntermittent claudicationIntermittent claudication

UnstableUnstableanginaangina}}ACSACS

ACS, acute coronary syndrome; TIA, transient ischemic attack

Efficacy of Antiplatelet Therapy:Efficacy of Antiplatelet Therapy:Antiplatelet Trialists’ CollaborationAntiplatelet Trialists’ Collaboration

Antiplatelet Trialists’ Collaboration BMJ 1994;308:81–106

Prior MIPrior MI 1111 1331/96771331/9677 1693/99141693/991425% (4)25% (4)

Acute MIAcute MI 99 992/9388992/9388 1348/93851348/938529% (4)29% (4)

Prior stroke/Prior stroke/ 1818 1076/58371076/5837 1301/58701301/587022% (4)22% (4)

TIATIA

Unstable angina Unstable angina 77 182/1991182/1991 285/2027285/2027

CategoryCategoryof trialof trial

No. ofNo. oftrialstrialswithwithdatadata

Anti-Anti-plateletplatelet

AdjustedAdjustedcontrolscontrols

Odds ratio andOdds ratio andconfidence intervalconfidence interval

(Antiplatelet:(Antiplatelet:control)control)

% odds% oddsreductionreduction

(SD)(SD)

MI, stroke, orMI, stroke, orvascular vascular

deathdeath

00 0.50.5 1.01.0 1.51.5 2.02.0

AntiplateletAntiplatelettherapytherapybetterbetter

AntiplateletAntiplatelettherapytherapyworseworse

TIA, transient ischemic attack

Complementary Mode of Action between Complementary Mode of Action between Clopidogrel and ASAClopidogrel and ASA

COX, cyclooxygenase; ADP, adenosine diphosphate; TxACOX, cyclooxygenase; ADP, adenosine diphosphate; TxA2, 2, thromboxane Athromboxane A2 2

Schafer AI Am J Med 1996;101:199–209

Trials of ADP-receptor Antagonists vs Trials of ADP-receptor Antagonists vs Placebo in Patients with AtherosclerosisPlacebo in Patients with Atherosclerosis

Trial, Year Setting Primary Outcome Odds Ratio

95% CI

Definition

Thieno-pyridine

(n/N)

Comparator (n/N)

Thienopyridine versus Placebo or Control

CATS 1989 (Ticlopidine vs Placebo

Recent Stroke

Death, MI,

Stroke

106/525 134/528 0.74 0.56-0.99

Balsano 1990 (Ticlopidine vs Control)

Unstable Angina

Death, MI

23/314 46/338 0.52 0.31-0.85

STIMS 1990 (Ticlopidine vs Placebo)

Intermittent Claudicatio

n

Death, MI,

Stroke

89/346 99/341 0.85 0.61-1.18

TOTAL 218/1185 279/1207 0.73 0.60-0.90CURE Study Investigators Eur Heart J 2000; 21: 2033-41.

Trials of ADP-receptor Antagonists vs ASA Trials of ADP-receptor Antagonists vs ASA in Patients with Atherosclerosis in Patients with Atherosclerosis

Trial, Year Setting Primary Outcome Odds Ratio

95% CI

Definition

Thieno-pyridine

(n/N)

Comparator (n/N)

Thienopyridine versus ASA

TASS, 1989 (Ticlopidine vs ASA)

Cerebral Ischemia

Death, Stroke

306/1529 349/1540 0.85 0.82-0.97

CAPRIE, 1996 (Clopidogrel vs ASA)

Recent Stroke,

Previous MI or PVD

Death, MI,

Stroke

939/9599 1021/9586 0.91 0.83-1.00

TOTAL 1245/11128

1370/11126 0.90 0.83-0.97

CURE Study Investigators Eur Heart J 2000; 21: 2033-41.

StudyStudy

HALL, 1996HALL, 1996

STARS, 1998*STARS, 1998*

TOTALTOTAL

0.10.1 1.01.0 10.010.0

Odds RatioOdds Ratio 95% CI95% CI

0.170.17 0.01-0.720.01-0.72

0.250.25 0.10-0.630.10-0.63

0.230.23 0.11-0.490.11-0.49

PP==0.00010.0001Test for heterogeneity Test for heterogeneity PP=0.66=0.66

ASA + Ticlopidine versus ASA after ASA + Ticlopidine versus ASA after Coronary Artery StentingCoronary Artery Stenting

Death or MIDeath or MI

CURE Study Investigators Eur Heart J 2000; 21:2033-41

Combination Better ASA Alone Better

•Randomized, double-blind, parallel group, clinical trial of clopidogrel vs placebo in patients with ACS

•All patients receive ASA (75-325 mg)

•International trial (28 countries)

•12,562 patients (482 Hospitals)

•Central randomization

•3-12 month Rx and follow-up

•Main outcomes: -CV death/MI, stroke

-Above + refractory ischemia

Study Design

Study ObjectivesStudy Objectives

To evaluate if clopidogrel is superior to placebo in preventing

a) CV death, MI, stroke (Primary at 0.045)

b) Above and refractory ischemia (Co-primary at 0.01)

Inclusion CriteriaInclusion Criteria

Ischemic symptoms, suspected to represent UA or MI without ST segment elevation

Randomized within 24 hours of onset of CP

and ECG evidence of ischemia at inclusion or already elevated cardiac enzymes or Troponin I or T to at least 2 x ULN*

* Prior to June 1999, pts > 60 yrs with normal ECG allowed

Revised July, 1999

Outcome Definitions (1/2)Outcome Definitions (1/2)CV Death: Excludes clear non-CV deaths

MI: Two of three usual criteria (CP, ECG or enzyme changes)

Stroke: Neurological deficit 24 hrs (CT/MRI encouraged)

Refractory Ischemia: Inhosp*: recurrent ischemia on max med Rx + ECG changes + intervention 1 day

After discharge: Rehosp for UA with ECG changes

Severe Ischemia*: Changes similar to in hospital Refractory Ischema, but no intervention

Recurrent Angina*: All other ischemic CP in hospital

Outcome Definitions (2/2)Outcome Definitions (2/2)

Major Bleeds: Significantly disabling, intraocular (vision loss), or transfusion of 2 units

Classified as Life Threatening if:

Hb > 5g/dl, hypotension needing IV inotropes, surgery to stop bleeding, symptomatic ICH or transfusion or 4 units of blood

Patient SchedulePatient Schedule

3 months double-blind treatment 12 months

Aspirin 75-325mg

Clopidogrel(~6,250 patients)

Placebo1 tab o.d.

(~6,250 patients)

Aspirin 75-325mgD

ay 1

6 m

. Vis

it9

m. V

isit

12 m

.

or F

inal

Vis

it

3 m

. Vis

it

Dis

char

ge V

isit

1 m

. Vis

it

Patients withAcute Coronary

Syndrome

(UA or MI Without STelevation)

R

load

ing

dose

300 mg loading + 75 mg o.d. dose

Baseline Characteristics (1)Baseline Characteristics (1)Placebo Clopidogrel

N=6303

%

N=6259

%

Male 61.7 61.3

Female 38.3 38.7

Unstable Angina 74.9 74.9

MI w/o ST Elevation 25.1 25.1

Abnormal ECG 93.9 93.7

Elevated enzymes/marker 25.3 25.3

Baseline Characteristics (2)Baseline Characteristics (2)Placebo Clopidogrel

N=6303

Mean (SD)

N=6259

Mean (SD)

Age 64.2 (11.3) 64.2 (11.3)

Heart rate 73.0 (14.6) 73.2 (14.8)

Systolic BP 134.1 (22.0) 134.4 (22.5)

Symptom onset to randomization (hrs) 14.1 (7.1) 14.2 (7.2)

Medications After Randomization Medications After Randomization in Hospitalin Hospital

Placebo Clopidogrel

% %

IV Heparin 46.9 46.0

LMW Heparin 56.0 56.1

Beta-blocker 78.4 78.7

Any CCB 36.0 36.0

ACE-I 49.9 50.9

Lipid-lowering 47.0 46.3

Outcomes 1 /2 Outcomes 1 /2 Plac Clop

% % RR CI p

# Patients 6303 6259

1st Co-Primary 11.41 9.30 0.80 0.72-0.90 < 0.001CV Death 5.47 5.08 0.93 0.79-1.08MI 6.65 5.18 0.77 0.67-0.89Stroke 1.38 1.20 0.86 0.63-1.18

Non CV death 0.71 0.66 0.91 0.60-1.39

Days of Follow-up

Cu

mu

lative

Ha

za

rd R

ate

s

0.0

0.0

10

.02

0.0

30

.04

0.0

50

.06

0 10 20 30

Cumulative Hazard Rates for CV Cumulative Hazard Rates for CV Death/MI/Stroke up to 30 DaysDeath/MI/Stroke up to 30 Days

P = 0.003

Clopidogrel

Placebo

Cum

ulat

ive

Haz

ard

Rat

es

Days of Follow-up

0 10 20 30

6303

6259

6108

6103

5998

6035

5957

5984

No. Plac

No. Clop

Months of Follow-up

Cu

mu

lative

Ha

za

rd R

ate

s

0.0

0.0

20

.04

0.0

60

.08

0.1

00

.12

0.1

4

0 3 6 9 12

Cumulative Hazard Rates for Cumulative Hazard Rates for CV Death/MI/StrokeCV Death/MI/Stroke

P < 0.001

Clopidogrel

Placebo

Cum

ulat

ive

Haz

ard

Rat

es

Months of Follow-up0 3 6 9 12

6303

6259

5780

5866

4664

4779

3600

3644

2388

2418

Plac

Clop

No of Pts

Outcomes 2/2Outcomes 2/2Plac Clop

% % RR CI p

# Patients 6303 6259

2nd Co-Primary 18.83 16.54

0.86 0.79-0.94 < 0.001

Refract.Ischemia 9.31 8.69 0.93 0.82-1.04

In hospital 2.00 1.36 0.68 0.52-0.90

After Discharge 7.59 7.57 0.99 0.87-1.13

Severe Ischemia 5.03 3.80 0.75 0.63-0.89 < 0.001

Bleeding ComplicationsBleeding ComplicationsPlacebo Clopidogrel RR 95% CI p

# Patients 6303 6259

Major 2.7% 3.7% 1.38 1.13-1.67 0.001Life Threatening

1.8% 2.2% 1.21 0.95-1.56 0.13

Other Major

0.9% 1.5% 1.70 1.22-2.35 < 0.002

Minor 2.4% 5.1% 2.12 1.75-2.56 < 0.001

Transfusion (2+Units)

2.2% 2.8% 1.30 1.04-1.62 0.02

TIMI Major Bleeding / GUSTO Severe-Life-TIMI Major Bleeding / GUSTO Severe-Life-Threatening Bleeding CriteriaThreatening Bleeding Criteria

Plac Clop RR

(95% CI)

P

# Patients 6303 6259

TIMI Criteria 73

(1.2%)

68 (1.1%)

0.94 0.70

GUSTO Criteria 70

(1.1%)

78

(1.2%)

1.12 0.48

Major/Life-Threatening Bleeds within 7 Major/Life-Threatening Bleeds within 7 Days of CABG SurgeryDays of CABG Surgery

Plac Clop RR p

Stopped < 5 days prior to CABG

N = 476 N = 436

Pts with Maj/LT Bleeds

6.3% 9.6% 1.53 0.06

Stopped > 5 days prior to CABG

N = 454 N = 456

Pts with Maj/LT Bleeds

5.3% 4.4% 0.83 0.53

Thrombocytopenia and Thrombocytopenia and NeutropeniaNeutropenia

Plac Clop

# Rand 6303 6259

Thrombocytopenia 28 (0.44%) 26 (0.42%)

Neutropenia 5 (0.1%) 8 (0.13%)

ScenarioScenario

67 year old man, non-Q MI Diabetes, HTN, dyslipidemia, ex-smoker

– No previous MI or CAD, but GI bleed– Was on ASA, other standard meds

Now 3 days post MI– Rx ASA, clopidogrel, stop enoxaparin, other

Rx standardDo you stop Clopidogrel?Do you stop Clopidogrel?

Users’ Guides for an Article Users’ Guides for an Article about Harmabout Harm

Are the results valid?– Similarity of all known determinants of

outcome or adjustments for differences in analysis?

– Were exposed patients equally identified?– Outcome assessment similar?– Was follow-up sufficiently complete?

Harm: Different Study DesignsHarm: Different Study DesignsDesignDesign Starting Starting

PointPointAssessmentAssessment StrengthsStrengths WeaknessesWeaknesses

Cohort Exposure status

Outcome event status

Feasible when randomization not possible

Susceptible to bias; limited validity

Case-Control

Outcome event status

Exposure status

Overcomes temporal delays; may only require small sample size

Susceptible to bias; limited validity

RCT Exposure status

Adverse event status

Lower susceptibility to bias

Feasibility and general-izability

Harm: Results and Harm: Results and ApplicabilityApplicability

What are the results?– How strong is the association between exposure and

outcome?– How precise is the estimate of the risk?

How can I apply the results to patient care?– Were the study patients similar to mine?– Was f/u duration adequate?– What is the magnitude of the risk?– Should I attempt to stop the exposure?

ScenarioScenario

67 year old man, non-Q MI Diabetes, HTN, dyslipidemia, ex-smoker

– No previous MI or CAD, but GI bleed– Was on ASA, other standard meds

Now 3 days post MI– Rx ASA, clopidogrel, stop enoxaparin, other

Rx standardDo you stop Clopidogrel?Do you stop Clopidogrel?

Who would ….Who would ….1.1. Stop Clopidogrel?Stop Clopidogrel?2.2. Continue it?Continue it?3.3. Don’t know….Don’t know….

Clopidogrel: NNT and NNHClopidogrel: NNT and NNHOutcomeOutcome ASA onlyASA only ASA andASA and

ClopidogrelClopidogrel

RRRRRR ARRARR NNT or NNT or NNHNNH

Primary .114 .093 .20

(.10-.28)

.021 47

MajorMajor

BleedBleed

.027.027 .037.037 .38 .38

(.13-.67)(.13-.67)

.01.01 100100

Clopidogrel: NNT and NNHClopidogrel: NNT and NNHOutcomeOutcome ASA onlyASA only ASA andASA and

ClopidogrelClopidogrel

RRRRRR ARRARR NNT or NNT or NNHNNH

Primary .114 .093 .20

(.10-.28)

.021 47

MajorMajor

BleedBleed

.027.027 .037.037 .38 .38

(.13-.67)(.13-.67)

.01.01 100100

Minor Minor BleedBleed

.024.024 .051.051 1.121.12

(.75-1.56)(.75-1.56)

.027.027 3737

Clopidogrel: NNT and NNHClopidogrel: NNT and NNHOutcomeOutcome ASA onlyASA only ASA andASA and

ClopidogrelClopidogrel

RRRRRR ARRARR NNT or NNT or NNHNNH

Primary .114 .093 .20

(.10-.28)

.021 47

MajorMajor

BleedBleed

.027.027 .037.037 .38 .38

(.13-.67)(.13-.67)

.01.01 100100

Minor Minor BleedBleed

.024.024 .051.051 1.121.12

(.75-1.56)(.75-1.56)

.027.027 3737

Our Patient ?? ?? .20

(.10-.28)

?? ??

TIMI Score for ACSTIMI Score for ACSwww.timi.tvwww.timi.tv or or www.timi.orgwww.timi.org

1. Age >= 65 years2. 3 CRF: (DM, HTN, Fam Hx, Lipid, smoker, )

3. Known CAD

4. Prior chronic ASA use

5. >= 2 episodes rest angina in 24h

6. Elevated Cardiac enzymes

7. ST deviation >= .5mm

TIMI Score for ACSTIMI Score for ACS1. Age >= 65 years2. 3 CRF: (DM, HTN, Fam Hx, Lipid, smoker, )

3. Known CAD

4. Prior chronic ASA use

5. >= 2 episodes rest angina in 24h

6. Elevated Cardiac enzymes

7. ST deviation >= .5mm

TIMI clinical prediction scoreTIMI clinical prediction score(14 days)(14 days)

TIMI ScoreTIMI Score Death/non-fatal MIDeath/non-fatal MI Death/non-fatal Death/non-fatal MI/revascularizationMI/revascularization

0/1 3% 5%

2 3% 8%

3 5% 13%

44 7%7% 20%20%

5 12 26%

6/7 19 41%

Clopidogrel: NNT and NNHClopidogrel: NNT and NNHOutcomeOutcome ASA onlyASA only ASA andASA and

ClopidogrelClopidogrel

RRRRRR ARRARR NNT or NNT or NNHNNH

Primary .114 .093 .20

(.10-.28)

.021 47

(31-87)

MajorMajor

BleedBleed

.027.027 .037.037 .38 .38

(.13-.67)(.13-.67)

.01.01 100100

Minor Minor BleedBleed

.024.024 .051.051 1.121.12

(.75-1.56)(.75-1.56)

.027.027 3737

TIMI 4 .07 [.056] [.20] [.014] [71]

WHAT ARE THE CONFIDENCE INTERVALS AROUND NNT?

Clopidogrel: NNT and NNHClopidogrel: NNT and NNHOutcomeOutcome ASA onlyASA only ASA andASA and

ClopidogrelClopidogrel

RRRRRR ARRARR NNT or NNT or NNHNNH

Primary .114 .093 .20

(.10-.28)

.021 47

(31-87)

MajorMajor

BleedBleed

.027.027 .037.037 .38 .38

(.13-.67)(.13-.67)

.01.01 100100

Minor Minor BleedBleed

.024.024 .051.051 1.121.12

(.75-1.56)(.75-1.56)

.027.027 3737

Our Patient

TIMI 4

.07 .063

[.056]

.10

[.20]

.28

.007

[.014]

142

[71]

Clopidogrel: NNT and NNHClopidogrel: NNT and NNHOutcomeOutcome ASA onlyASA only ASA andASA and

ClopidogrelClopidogrel

RRRRRR ARRARR NNT or NNT or NNHNNH

Primary .114 .093 .20

(.10-.28)

.021 47

(31-87)

MajorMajor

BleedBleed

.027.027 .037.037 .38 .38

(.13-.67)(.13-.67)

.01.01 100100

Minor Minor BleedBleed

.024.024 .051.051 1.121.12

(.75-1.56)(.75-1.56)

.027.027 3737

Our Patient

TIMI 4

.07 .063

[.056]

.05

.10

[.20]

.28

.007

[.014]

.02

142

[71]

51

Months of Follow-up

Cu

mu

lative

Ha

za

rd R

ate

s

0.0

0.0

20

.04

0.0

60

.08

0.1

00

.12

0.1

4

0 3 6 9 12

Cumulative Hazard Rates for Cumulative Hazard Rates for CV Death/MI/StrokeCV Death/MI/Stroke

P < 0.001

Clopidogrel

Placebo

Cum

ulat

ive

Haz

ard

Rat

es

Months of Follow-up0 3 6 9 12

6303

6259

5780

5866

4664

4779

3600

3644

2388

2418

Plac

Clop

No of Pts

Initial benefit then 20% relative over 11 months

TIMI clinical prediction scoreTIMI clinical prediction score(14 days)(14 days)

TIMI ScoreTIMI Score Death/non-fatal MIDeath/non-fatal MI Death/non-fatal Death/non-fatal MI/revascularizationMI/revascularization

0/1 3% 5%

2 3% 8%

3 5% 13%

44 7%7% 20%20%

5 12 26%

6/76/7 1919 41%41%

Clopidogrel: NNT and NNHClopidogrel: NNT and NNHOutcomeOutcome ASA onlyASA only ASA andASA and

ClopidogrelClopidogrel

RRRRRR ARRARR NNT or NNT or NNHNNH

Primary .114 .093 .20

(.10-.28)

.021 47

MajorMajor

BleedBleed

.027.027 .037.037 .38 .38

(.13-.67)(.13-.67)

.01.01 100100

Minor Minor BleedBleed

.024.024 .051.051 1.121.12

(.75-1.56)(.75-1.56)

.027.027 3737

Our Patient

TIMI 4

.07 .056 .20

(.10-.28)

.014

(.007-.02)

71

(51-142)

TIMI 6 .19 .15 .20

(.10-.28)

.04

(.019-.053)

25

(18-52)

TIMI in TACTICS (6mo)TIMI in TACTICS (6mo)

TIMITIMI ConservativeConservative InvasiveInvasive

0-20-2 5%5% 5%5%

3-43-4 10%10% 7%7%

5-75-7 15%15% 12%12%

TIMI and PRISM-PLUSTIMI and PRISM-PLUS

TIMITIMI UFHUFH Tirofiban + Tirofiban + UFHUFH

0-20-2 6%6% 5%5%

3-43-4 9%9% 7%7%

5-75-7 15%15% 9%9%

Non-ST Elevation ACSNon-ST Elevation ACS

When do you add Clopidogrel? When do you stop Clopidogrel? How do you place Clopidogrel in relation to other

expensive/potentially risky interventions:– angiogram– LMW heparin– IV G2b3 inhibitors

Do you put Clopidogrel on formulary

Community GIMCommunity GIM

My HistoryCommunity vs Tertiary Clinical PracticeResearchTeachingLifestyleOptions / Electives

Tertiary vs Community GIMTertiary vs Community GIM

Scut/hospitalist Few offices Few procedures Onerous Call Ponies and Horses Looked down by

subspecialists Access to journals

Consultant Office at least 50% Many choices Paid call as consultant Horses, Zebras and Gnus Valued by subspecialists

Full access to journals

CLINICAL RESEARCH PROJECTS Multicenter Studies: 1. Primary Site Investigator, ESSENCE study (completed). 1993-4.2. Primary Site Investigator, GUSTO-III study (completed). 1994-5.3. Primary Site Investigator, PAT study (completed). 1995-7.4. Primary Site Investigator, OASIS-2 study (completed). 1995-7.5. Primary Site Investigator, SYMPHONY 1 study (completed). 1997-8.6. Primary Site Investigator, TAIS study (completed). 1995-8.7. Primary Site Investigator, SYMPHONY 2 study (completed). 1998-9.8. Primary Site Investigator, HOOD study (ongoing). 1993- 9. Primary Site Investigator, LITE/Home-LITE study (ongoing). 1995-10. Primary Site Investigator, PEACE study (ongoing). 1996-11. Primary Site Investigator, CURE study (completed). 1999-2001.12. Primary Site Investigator, CHARM study (ongoing). 1999-13.               Primary Site Investigator, GUSTO-IV study (ongoing). 1999-14.               Primary Site Investigator, WAVE study (ongoing). 2000-15.               Primary Site Investigator, EPHESUS study (ongoing). 2000-16.               Primary Site Investigator, PREVENT study (ongoing). 2000-17.               Primary Site Investigator, HOPE-TOO study (ongoing). 2000-18.               Primary Site Investigator, DREAM study (ongoing). 2001-19.               Primary Site Investigator, POISE study (ongoing). 2001-20.               Primary Site Investigator, INTERACT study (ongoing). 2001-21.               Primary Site Investigator, COMPETE-CHIPP project, McMaster University (ongoing). 22.               Primary Site Investigator, ONTARGET/TRANSCEND

 Funded Local Studies:        Principal Investigator, GHC polypharmacy audit (PSI funding, $4000).       Principal Investigator, GHC Diabetic Continuity of Care Study (CHSRF funding, $518,000 over three years).       Principal Investigator, GHC/SAH applied research education grant (CHSRF funding, $30,000).       Co-director, GHC Health Promotion Initiative Programs (GHC $122,000).       Principal Investigator, CHF discharge transition project (PSI funding, $5600).       Principal Co-Investigator, Northern Health Research Grant for determinants of cardiovascular disease in Sault Ste Marie 2000, (joint Lakehead, McMaster universities, $5000).       Principal Investigator, Validation of the Osteoporosis Risk Assessment Index. (Proctor Gamble, $5000).       Principal Investigator, Audit and Development of Atrial Fibrillation Risk Assessment Index. (Dupont, $5000).       Principal Investigator, Optimization of Secondary Prevention of Cardiac Events in CAD, (Pfizer, $6000).       Principal Investigator, Evidence Based Diabetes Lipids Management, (Merck, $5000).       Co-Principal Investigator, Evaluating Teletriage in Northern Ontario. (Richard Ivey Foundation, $162,000).

PUBLICATIONS: 1992, 1994 Chief Editor: Survival Guide, McMaster University ... (Still published, fourth edition). 1. Heyland D., Cook D.J., Jaeschke R., Lee H.N., Griffith L., Guyatt G.G. Selective Decontamination of the Digestive Tract: An Overview. Chest 1994; 105:1221-9.2. Levine M, Walter S, Lee H, Haines T, Holbrook A, Moyer V. User’s Guides to the Medical Literature IV: How to use an article about harm. JAMA 271(20):1615-9;1994:May 25.3. User’s Guides Working Group, JAMA series 1993-1995.4. Lee HN, Cook DJ, Sarabia A, Hatala R, McCallum A, King D, Guyatt GH, Dobranowski J, Powers P. Inadequacy of intravenous heparin therapy in the initial management of venous thromboembolism. Journal of General Internal Medicine. 10(6):342-5, 1995 Jun. 5. Sauve H., Lee H.N. et al. The Critical Appraisal Topic: A Tool for Evidence Based Medicine. Ann R. College 1995.6. EBM Pocket Guide, Sault Ste Marie, 1997.7. EBM Workbook, Sault Ste Marie, 1997. Presented/Published Abstracts 1. Lee H.N., Cook D.J., Brill-Edwards P., Neville A. The Development of objective-linked behaviour-specific evaluation forms for residents on a clinical teaching unit. Clinical Research 1993;41(2):560A.2. Lee H.N., Lang J.D., Cook D.J. Characterization of Patient Care in a Medical Clinical Teaching Unit. Clinical Research 1993; 41(2):560A.3. Lee H.N., Ganesan C., Hatala R., Sarabia, McCallum A., Cook D.J. The initial management of venous thromboembolism: A study of factors leading to inadequate heparinization. Clinical Research 1993;41(2):543A.4. Lee H.N., Sauve J.S., Farkouh M.E., Sackett D.L. The Critically Appraised Topic: A standardized aid for the presentation and storage of evidence-based medicine. Clinical Research 1993; 41(2): 543A.5. Lee H.N., Churchill D, Adachi R.D., Thorpe K. Change in Lumbar spine bone mineral content of hemodialysis patients after parathyroidectomy. Clinical Research 1993;41(2):358A.6. Hunt D.L., Lee H.N., Sauve J.S., Farkouh M.E., Sackett D.L., Neural Network diagnosis of iron-deficiency anemia in the elderly: Comparison with conventional epidemiological methods. Clinical Research 1993;41(2):526A.7. Farkouh M.E., Sauve J.S., Kassam H., Lee H.N., Sackett D.L. Varying formats in which trial results are reported can affect clinical decision making. Clinical Research 1993;41(2):517A.8. Sauriol N, Lee HN. An audit of the acute management of myocardial infarction in a northern community. RCPSC Annual Meeting, Toronto, 1998.9. Catania A, Wallenius S, Lee HN. An audit of polypharmacy in a community health centre. Society of General Internal Medicine (SGIM) Annual Meeting, San Francisco, 1999.10. Olivier K, Lee HN. Utility of the Stress Test in a primary care setting. SGIM Annual Meeting, San Francisco, 1999.11.                 Shiau J, Wallenius S, Lee HN. A Randomized Controlled Trial of an Electronic Template to Improve Evidence Based Health Interventions in Patients with Diabetes. (SGIM, Boston 2000, CDA Annual Meeting, Halifax 2000).12.                 Lee HN for the CHIC investigators. SF-36 Quality of Life and association with Continuity of Care and Quality of Care in Diabetes. (CDA Annual Meeting, Halifax October 2000).13.                 Lee HN, Bragaglia P, Wetzl T, Apostolon C. A community-based registry of Adult Patients with Diabetes. (CDA Annual Meeting, Halifax, October 2000).14.                 Flintoft V, Lee HN, Sridhar F, Lee D. Systematic Review: Multidisciplinary Discharge Transition Programs decrease hospital readmission for heart failure patients. (SGIM Annual Meeting, San Diego, 2001).15.                 Chau, J, Lee HN. Balancing the Risks and Benefits of Anticoagulation in Elderly Patients with Atrial Fibrillation. (SGIM Annual Meeting, San Diego, 2001).16.                 Lee HN, Garniss D, Oliver R, McCullogh C, Dulisse D. A Community Hospital-Based Heart Failure Program Decreases Readmission Rates. (SGIM Annual Meeting, San Diego, 2001).

Lee HN, Wilson C, Ciaschini P, Hemy M, Mogharrabi V. Validation of the Osteoporosis Risk Assessment Index in the Community. (SGIM Annual Meeting, San Diego, 2001).

TEACHINGTEACHING

Med studentsFamily Medicine studentsGIM / Core IM electives and …NEW Northern Community GIM program

starting July 2002NEW Northern Ontario & Rural Medical

School starting July 2004

LifestyleLifestyle

Family – commitments to workRenumeration / quality of lifeLocation:

– Spousal employment– Climate– Safety– Recreation– Commuting

Electives and other optionsElectives and other options

Northern Specialty Electives– Paid travel, accommodations– Other residents– Free Internet and eJournal access– Families considered also

Northern Community GIM Residency– July 2002– advice