Acute Coronary Syndrome Registries Closing the GAP between Guidelines and Practice

1
Acute Coronary Syndrome RegistriesClosing the
GAP between Guidelines and Practice

• David Fitchett MD
• St Michaels Hospital and
• Canadian Heart Research Centre

2
Acute Coronary Syndromes
Suspected ACS
Presentation
Adapted from Braunwald et al J Am Coll Cardiol
2002
positive cardiac enzymes/markers
3
Background why Registry

• Randomized clinical trials revolutionize the
  treatment of acute coronary syndromes (ACS)
• Unclear how research-based evidence applies to
  real world practice in Canada
• Management and outcome of ACS patients after the
  acute phase have not been well described

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What can we learn from Registries ?

• Epidemiology of acute coronary disease
• Diagnosis
• Accuracy of ECG interpretation
• Validation of Risk models
• Management
• What is being used and are there trends ?
• Outcomes when guidelines are followed
• Outcomes and management of high risk groups
• Older
• Diabetic
• Chronic Kidney Disease
• Change practice to follow evidence based
  guidelines

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Early Mortality inNon-ST? ACS
of Patients
6
7-day
In-hospital
5
4
3
2
1
n9,461
n1,915
n7,800
n27,786
0
PURSUIT
PRISM-PLUS
GUSTO IV-ACS
CRUSADE
6
Leading and Lagging Hospital Quartiles Acute Care
of Patients
100
80
60
40
20
0
ASA lt24 hrs
? Blocker lt24 hrs
Heparin
Clopidogrel
GP IIb/IIIa
Roe et al
7
Leading and Lagging Hospital Quartiles Discharge
Care
of Patients
100
94
89
80
82
78
67
68
60
60
58
49
40
36
20
0
ASA
? Blocker
ACE Inhibitor
Statin
Clopidogrel
LVEF lt 40 Known hyperlipidemia
Roe et al
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Performance Matters!Relationship between Process
and Outcome
In-hospital Mortality
of Patients
8
6
4
2
0
lt65
65-75
75-80
gt80
Hospital Composite Adherence Quartiles
Roe et al
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ACS Registry

• Canadian, multicentre, prospective, observational
  registry of clinical management practices and
  patient outcomes in ACS
• Designed to collect, analyze, and disseminate
  data on Canadian ACS patients

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Canadian ACS Registry
5,312 patients 51 sites (Sept 1999-June 2001)

Newfoundland
New Brunswick 4 sites n333
British Columbia7 sites n942
Saskatchewan 1 site n249
Quebec 9 sites n1360
P.E.I 1 site n101
Manitoba1 site n26
Alberta4 sites n394
Ontario 22 sites N1780
Nova Scotia2 sites n127
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Final Diagnosis
Non-cardiac
Other Cardiac
5.2
Q Wave MI
7.7
24.2
Unstable Angina
Non-Q Wave MI
34
28.9
N 5,312
Overall 4627 (87.1) had a final ACS diagnosis
(in-hospital mortality rate 2.4) 2925 patients
had NSTE ACS (in-hospital mortality rate 1.5)
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ACS Registry I

• First phase provided important information about
• level of risk (e.g., based on ECG and cardiac
  marker status)
• management strategies employed (e.g., initial
  anti-platelet/thrombotic treatment, coronary
  angiography and revascularization)
• short and long-term outcomes in ACS patients on a
  Canada-wide basis
• Results indicate that, despite clear guidelines
  and evidence from clinical trials, the majority
  of patients are not optimally managed

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Multivariable Logistic Regression Model to
Predict 1-year Mortality
Independent Predictors

• Variables Odds Ratios (95 CI) P value
• Age (per decade) 1.59 (1.34-1.90) lt0.001
• Previous MI 1.45 (1.08-1.93) 0.012
• Diabetes 1.52 (1.13-2.03) 0.005
• Previous CHF 1.60 (1.11-2.31) 0.012
• Systolic BP (per 10mmHg) 0.95 (0.91-1.00) 0.03
• Killip class II 1.64 (1.19-2.26) 0.003
• Killip class III 1.54 (0.86-2.75) 0.15
• Killip class IV 4.15 (1.37-12.5) 0.012
• ST deviation/BBB 1.48 (1.11-1.97) 0.007
• Abnormal biomarker 2.21 (1.55-3.16) lt0.001
• CrCl 1.19 (1.11-1.27) lt0.001

Hosmer-Lemeshow goodness-of-fit P 0.22
Per 10 ml/min decrease
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Medication Use at Discharge and 1-year Mortality

• After adjusting for age, previous MI, CHF, Killip
  class, abnormal biomarker, ST deviation/BBB on
  presentation, the discharge use of the following
  medications was associated with lower 1-year
  mortality
• ASA OR0.48 (0.36 to 0.63), Plt0.001
• Beta-blocker OR0.72 (0.56 to 0.92), Plt0.01
• ACE inhibitor OR0.76 (0.60 to 0.96), P0.02
• Lipid lowering agent OR0.72 (0.57 to 0.92),
  Plt0.01

OR odds ratio (95 confidence interval)
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ACS Registry II

• The second phase of the ACS Registry is designed
  to close, at least in part, this care gap by
  continuing the educational effort and supporting
  it with specific management recommendations based
  on risk assessment

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CHRC ACS Registry II
2356 ACS patients 36 sites (Oct 4, 2002 Dec 17,
2003)

New Brunswick 1 site n50
British Columbia8 sites n868
Saskatchewan 1 site n13
Quebec 8 sites n484
Manitoba1 site n95
Alberta3 site n22
Ontario 14 sites n824
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Patient Selection

• Consecutive patients admitted (or designated for
  admission) with a diagnosis of a non-ST segment
  elevation acute coronary syndrome (NSTE ACS)
• ?18 years old AND,
• diagnosed with a NSTE ACS as defined by symptoms
  felt to be consistent with acute cardiac ischemia
  within 24 hours on symptom onset AND,
• The qualifying acute coronary syndrome must not
  have been precipitated or accompanied by a
  significant co-morbidity (e.g., trauma,
  gastrointestinal bleeding, peri-operative or
  peri-procedure MI)

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Case Selection Strategy

• First 10 consecutive qualifying cases in each
  month
• Confirm inclusion criteria
• Patient consent for follow-up
• Enroll patient
• 12-month follow-up by telephone

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Acute coronary Syndromes Strategy for
Evidence-based Risk stratification and Treatment
(ASSERT) Program (1)

• To facilitate attainment of the Registry
  objectives, the ASSERT program includes provision
  of
• standing orders template for non-ST segment
  elevation ACS
• poster and pocket cards summarizing an
  evidence-based approach to the initial management
  of NSTE ACS patients

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Acute coronary Syndromes Strategy for
Evidence-based Risk stratification and Treatment
(ASSERT) Program (2)

• A PowerPoint? slide set with detailed speakers
  notes that contains
• Information on the evidence-to-practice gap and
  how we as a medical community can potentially
  close this gap
• Some simple approaches to risk stratification
  that facilitate the choice of treatments and
  management strategies and,
• Data from several recent clinical trials
  supporting an evidence-based medicine approach to
  treatment and,
• A list of key references

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Risk Management Assessment (RMA) portion of the
Case Report Form
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Risk Stratification for Non-ST? ACS
30-Day Death/MI
Level
Features
Prolonged/ongoing ischemic discomfort with high
risk features transient ST? or ST? ?1 mm in ?2
leads sustained ST depression ?2 mm T wave
inversion ?1 mm in ?5 leads positive cardiac
markers recurrent ischemia acute MI in past 4
weeks hemodynamic compromise (e.g., heart
failure or hypotension)
Higher
12-30
Ongoing ischemic discomfort but no high risk
features crescendo angina preceding rest pain
borderline positive troponin previous
percutaneous coronary intervention or coronary
artery bypass surgery increased baseline risk
(e.g., diabetes, age ?60 years)
Intermediate
4-8
No high risk or intermediate risk features
single episode of chest discomfort at rest, or
crescendo exertional angina ECG normal or
non-specific abnormalities or unchanged from
previous may include patients with history of
known CAD or with risk factors for CAD
Lower
lt2
Modified from Fitchett et al Can J Cardiol
2000161423-32 and CMAJ 20011641309-16
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Risk Management Approach
Evidence-Based Medicine Recommendations
High
Inter.
Low
ASA (Aspirin)
?
?
?
Clopidogrel Medical treatment
?
?
Clopidogrel Post-stent
?
?
?
?
Heparin Enoxaparin
?
GP IIb/IIIa Inhibitor Medical treatment
?
GP IIb/IIIa Inhibitor PCI
?
?
?
Enoxaparin superior to unfractionated
heparin Eptifibatide or tirofiban Eptifibatid
e or abciximab
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Risk Management Approach
Evidence-Based Medicine Recommendations
High
Inter.
Low
?-blocker
?
?
?
ACE inhibitor
?
?
?
?
?
?
Statin
?
Cardiac cath referral Initial 24 hours
?
Cardiac cath referral In-hospital
?
If CAD is proven In setting of LV dysfunction
(EFlt40) and/or congestive heart failure (CHF)
captopril, enalapril, lisinopril, ramipril, or
trandolapril in setting of CAD without LV
dysfunction and/or CHF ramipril In setting of
acute coronary syndromes (ACS) atorvastatin in
setting of post-ACS pravastatin or simvastatin
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Treatment/ management
If not given, why? (Use coding system)
þ
o
þ
o
þ
o
oo
o
o
X
þ
o
oo
o
o
X
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Anti-Thrombotic/Platelet Therapy in the First 24
Hours
Non-ST? (n3,488)
of Patients
100
90
80
60
51.7
40
35.9
20
4.8
8.3
0
Clopid./ Ticlop.
ASA
UFH
LMWH
IIb/IIIa
Sept 1999 June 2001
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Reasons Why Low Molecular Weight Heparin Has NOT
Been Prescribed

• General
• Allergy or intolerance
• Renal insufficiency
• Patient not high enough risk
• Clinical trial evidence doesnt support use
• Other safety concerns not specified below

• Antiplatelet/thrombotic
• Active bleeding
• Recent surgery or trauma
• History of bleeding disorder/coagulopathy
• History of prior stroke/TIA
• Thrombocytopenia
• Anemia
• Severe hypertension
• Treatment with warfarin

• LMWH
• Concomitant GP IIb/IIIa inhibitor use
• Planned invasive procedure

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Reasons Why Patients Are NOT Receiving LMWH
(n565) Not high risk enough Planned invasive
procedure GP IIb/IIIa Inhibitor use Renal
insufficiency Bleeding risk Other safety
concerns Patient/family refused
48.5 16.1 6.9 6.4 9.7 12.2 0.4
Including clinical evidence/guidelines dont
support Including active bleeding, recent
surgery/trauma, bleeding disorder/coagulopathy,
anemia, thrombocytopenia, on warfarin
Including other comorbid conditions, prior
stroke/TIA, severe hypertension
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Patients NOT Receiving LMWH Because Not High
Enough Risk
of Patients
25
n312
20
15
10
5
0
Low
Intermediate
High
0-2
3-4
5-7
TIMI Risk Score
Estimated 14-day Death/MI
2.9
4.7-6.7
11.5-19.4
Including clinical evidence/guidelines dont
support
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Reasons Why Clopidogrel Has NOT Been Prescribed

• General
• Allergy or intolerance
• Renal insufficiency
• Patient not high enough risk
• Clinical trial evidence doesnt support use
• Other safety concerns not specified below

• Antiplatelet/thrombotic
• Active bleeding
• Recent surgery or trauma
• History of bleeding disorder/coagulopathy
• History of prior stroke/TIA
• Thrombocytopenia
• Anemia
• Severe hypertension
• Treatment with warfarin

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Reasons Why Patients Are NOT Receiving Clopidogrel
65.8 13.7 17.1 3.8 0.1
(n850) Not high risk enough Bleeding
risk Other safety concerns Planned invasive
procedure GP IIb/IIIa inhibitor use
Including clinical evidence/guidelines dont
support Including active bleeding, recent
surgery/trauma, bleeding disorder/coagulopathy,
anemia, thrombocytopenia, on warfarin
Including other allergy/intolerance, renal
insufficiency, co-morbid conditions, prior
stroke/TIA, severe hypertension
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Use of Clopidogrel ?24 Hrs By Presenting Risk
of Patients
100
80
60
40
20
0
GRACE Risk Score
High n688
Intermediate n688
Low n688
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Anti-Thrombotic/Platelet Therapy at Discharge
All ACS (4,518)
Non-ST? (n2,356)
of Patients
of Patients
100
100
87.7
80
80
60
60
40
40
22.4
20
20
8.7
0
0
ASA
Clopidogrel/ Ticlopidine
Warfarin
ASA
Clopidogrel/ Ticlopidine
Warfarin
34
Preliminary Results
Medical Therapy at Discharge
of Patients
100
80
81.8
75.8
60
62.9
40
28.3
27.6
20
9.6
6
0
Beta blocker
Calcium blocker
Diuretic
ACE inhibitor
ARB
Statin
Other lipid
lowering
35
Preliminary Results
Lipid Lowering Use
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Reasons Why A Statin Has NOT Been Prescribed

• Statin
• No hypercholesterolemia (i.e., treatment not
  indicated based on Canadian Working Group
  recommendations
• Treatment with other lipid lowering agent
• Abnormal liver function tests indicating hepatic
  pathology

• General
• Allergy or intolerance
• Renal insufficiency
• Patient not high enough risk
• Clinical trial evidence doesnt support use
• Other safety concerns not specified below

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Reasons Why Patients Are NOT Receiving Treatment
Statin
(n534) Patient not high risk enough No
hypercholesterolemia On another lipid-lowering
agent Allergy/Intolerant Abnormal Liver function
test(s) Other comorbid conditions Other safety
concerns
21.2 47.1 11.9 2.2 2.4 5.3 7.5
Including evidence or guidelines dont support
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Conclusions

• Registries provide unselected real world data
• ACS management frequently discordant with
  guidelines
• Management orientated registries provide means to
• Inform
• Close management GAP
• Improve patient outcomes