Download Knowledge is the Enemy of Disease

Challenges and Opportunities for
Observational Research:
The BRIDGE-CV
Prevention
Study
Otavio Berwanger (MD; PhD)
Director
Research Institute – Heart Hospital- HCor
São Paulo-SP, Brazil
Knowledge is the Enemy of
Disease
(Sir Muir Gray –UK)
1
Knowledge is the Enemy of
Disease
Practicing EBM – the 4 A’s
Step 4
Step 3
Step 2
Step 1
Ask a
clinical
question
Acquire
the best
evidence
Appraise
the
evidence
Apply
the
evidence
2
Evidence that
gets incorporated
into practice
Available evidence
5
Barriers to physician adherence to
practice guidelines in relation to behavior change
Sequence of
behavior
change
Barriers to
guideline
adherence
Knowledge
Lack of familiarity
Volume of information
Time needed to stay
informed
Guideline accessibility
Lack of awareness
Volume of information
Time needed to stay
informed
Guideline accessibility
Attitudes
Lack of agreement
with specific
guidelines
Interpretationof
evidence
Applicability to
patient
Not cost-beneficial
Lack of confidence in
guideline developer
Lack of agreement
with guidelines in
general
Too cookbook
Too ridid to apply
Biased synthesis
Challenge to
autonomy
Not practical
Behavior
Lack of outcome
expectancy
Physician belives
that performance of
guideline
recommendation
will not lead to
desired outcome
Lack of selfefficacy
Physician belives
that he/she cannot
perform guideline
recommendation
Lack of
motivation/inertia
of previous
practices
Routines
Habit
External barriers
Inability to
reconcile patient
preferences with
guideline
recommendations
Guideline factors
Guideline
characteristics
Presence of
contradictory
guidelines
Enviromental
factors
Lack of time
Lack of resources
Organizational
constraints
Lack of
reimbursement
Perceived increase
in malparctice
liability
Cabana M et Al. JAMA 1999; 282 (15): 1458-1465
3
Many “Leaks” from Evidence to Practice
Aware Accept Target Doable Recall Agree Done
Valid
Research
If 80% achieved at each stage then
0.8 x 0.8 x 0.8 x 0.8 x 0.8 x 0.8 x 0.8 = 0.21
Glasziou and Haynes – Evidence Based Medicine (3rd Ed)
Geographic Practice Variation:
Discharge Medication
100
United States
94
93 94 93
Australia/New Zealand/Canada
Europe
80
Patients (%)
Argentina/Brazil
60
47
49
54
53
53
57
50
40
26
20
0
**P<0.01
ACE
AT/AC, antithrombin or anticoagulant
Statin
AT/AC
Fox KAA et al. Eur Heart J 2002;23:1177-89.
4
Proportion of Patients Receiving 100% of All
Guidelines-Recommended Therapies*
100%
Q1
Q4
Q8
Q11
75%
46% 48%
50%
31%
25%
36%
33%
50%
47%
34%
30%
30%
21%
16%
0%
Overall 100% Correct
Medication
Acute 100% Correct
Medication
Discharge 100% Correct
Medication
Mehta et al, AHA 2005
*In patients without contraindications
Hospital Link Between Overall Guidelines
Adherence and Mortality
% In-Hosp Mortality
7
6
5,95
6,31
5,16 5,06
5
4,97
4,63
4,16 4,15
4
3
2
Every 10%  in guidelines adherence 
10%  in mortality (OR=0.90, 95% CI: 0.84-0.97)
1
0
<=25%
25 - 50%
50 - 75%
>=75%
Hospital Composite Quality Quartiles
Adjusted
Unadjusted
Peterson et al, JAMA 2006;295:1863-1912
5
VBWG
Evidence-based medications in ACS
patients: Effect on 6-month mortality
N = 1358
Appropriateness
level*
Lower mortality
Higher mortality
n
IV
630
0.10 (0.03–0.42)
III
314
0.17 (0.04–0.75)
II
302
0.18 (0.04–0.77)
I
91
0.36 (0.08–1.75)
0.0
0.5
1.0
1.5
2.0
3.0
Odds ratio (95% CI)
* Number of evidence-based medications used
(aspirin, ACE inhibitor, -blocker, statin) vs number indicated
Mukherjee D et al. Circulation.
2004;109:745-9.
Drugs by Regions
%
Statins
PURE Study. Yusuf et al. Lancet. 2011;378:1231-43
6
Brazilian Registry of High Cardiovascular
Outpatients
(Patients with previous CAD, Cerebrovascular
Disease, PAD or Multiple Risk Factors)
N= 5030 Consecutive Patients
48 centers from all Brazilian Regions
Baseline
Patients with concomitant use of Aspirin / Statin / ACEI
X
Clinical History
100%
34%
66%
80%
Yes
No
60%
40%
40.1%
35.6%
35.1%
31.7%
Stroke/TIA
DM
PVD
20%
0%
CAD
Berwanger O et at. Arq Bras Cardiol 2013
7
RISK FACTOR CONTROL
BP >=140/90 mmHg (Hypertensive patients)
38.4%
LDL >= 100mg/dL (CAD)
46.0%
LDL >= 100mg/dL (Previous Stroke)
42.0%
LDL >= 100mg/dL (PAOD)
41.3%
LDL >= 100mg/dL (Diabetic patients)
39.3%
Hemoglobin a1c >=7% (Diabetic patients)
50.8%
Glucose >= 110 (Diabetic patients)
0.0%
67.7%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
EVIDENCE-BASED THERAPIES AND OUTCOMES
N= 5030
ASA 6M
STATIN 6M
STATIN AND ASA 6M
ACEi 6M
AGE
GENDER (MALE)
DIABETES
DYSLIPIDEMIA
AMI
STROKE
PAOD
CV Mortality, Non-Fatal MI, or Non-Fatal Stroke at 12 months
8
Practice
Evidence
The Quality Gap
Systematic review of guideline
dissemination and implementation
strategies
Intervention
Number of
Cluster RCTs
Median
effect size
Range
Educational
materials
5
+8.1%
+3.6%, +17.0%
Audit and
feedback
5
+7.0%
+1.3%, +16.0%
Reminders
14
+14.1%
–1.0%, +34.0%
Grimshaw et al. Cochrane EPOC Group
9
Late-Breaking Clinical Trials
Session- ACC 2012, Chicago
34 Clusters (Public General Hospitals) including 1,150 consecutive
patients with ACS
Concealed Randomization
Multifaceted Quality
Improvement Intervention
(n= 17 clusters and 602 patients)
Routine Practice
(n= 17 clusters and 548 patients)
ITT
ITT
Primary Endpoint: Adherence to all eligible evidence-based therapies during the
first 24 hours
Secondary Endpoints: Adherence to all eligible evidence-based therapies during
the first 24 hours and at discharge, composite EBM score, major cardiovascular
events
Berwanger O et al. JAMA 2012; 307:2041-9
10
Multifaceted Quality Improvement Intervention
Colored Bracelet (according to the
risk stratification
“Chest Pain” Label
Checklist
Pocket Guidelines
Case Manager
Poster
Results
Intervention
ORPA = 2.64 (1.28–5.45) ICC = 0.32
Control
ORPA = 2.49 (1.08–5.74) ICC = 0.36
80.0%
70.0%
67.9%
60.0%
50.0%
49.5%
40.0%
50.9%
31.9%
30.0%
20.0%
p = 0.01
p = 0.03
Adherence to all acute evidencebased therapies
Adherence to all acute and discharge
therapies
10.0%
0.0%
Berwanger O et al. JAMA 2012; 307:2041-9
11
BRIDGE – CV
Prevention
BRIDGE Cardiovascular Prevention
A cluster randomized trial evaluating the effect of a
multifaceted intervention to increase evidence based
strategies usage for cardiovascular prevention
Study Design and Objectives
Pragmatic cluster randomized controlled trial, with web based central
randomization and allocation concealment, blinded outcomes assessment
and validation, intention to treat analysis.
• Primary Objective: To assess the impact of a multifaceted
intervention in adherence to evidence based therapies
prescription for cardiovascular prevention in high risk patients
for (lipid lowering agents, anti platelets and ACE Inhibitors)
in 12 months.
• Secondary Objectives: To assess the impact of and
educational multifaceted intervention for improving the
prescription of lipid lowering agents, anti platelets and ACE
inhibitors in reducing cardiovascular events.
12
Eligibility
• Patients:
• Clusters :
Outpatient clinics
(including internal
medicine, cardiology,
endocrinology or
vascular neurology)
from public and private
hospitals or primary
care centers in Brazil.
– over 40 years old;
– High cardiovascular risk:
• Any evidence of coronary artery
disease ;
• Any evidence of ischemic stroke or
transient ischemic attack (TIA) ;
• Peripheral Artery Disease (PAD);
• Diabetes Mellitus;
• Three cardiovascular risk factors,
except diabetes:
–
–
–
–
–
–
Systemic Arterial Hypertension;
Smoking;
Dyslipidemia;
Age over 70 years old;
Diabetic nephropathy;
Familial history of coronary artery
disease;
– Assymptomatic carotid disease
Brazilian Sites
NORTH = 03
NORTH EAST = 10
CENTRAL= 03
SOUTH EAST = 25
SOUTH = 15
13
Outcomes
Primary Outcome:
Secondary Outcomes:
Adherence to evidence based
therapies
(aspirin/antiplatelets, lipid
lowering agents and ACE
inhibitors) in an “all or
none” model for patients
without contra indication in
a period of 12 months.
•
•
•
•
•
•
•
•
•
Adherence to lipid lowering agents, aspirin and
ACE Inhibitors in 03 and 06 months for patients
without contra indications (Composite
Adherence Score).
Proportion of eligible patients with LDL <
100mg/dL in 12 months
Adherence to lipid lowering agents prescription
Adherence to antiplatelet therapy
Adherence to ACE inhibitors prescription
Adherence to high dose statins prescription
LDL < 100mg/dL in 03, 06 and 12 months after
admission.
LDL < 70 mg/dL in 03, 06 and 12 months after
admission.
Clinical Events Composite Outcome
(cardiovascular deaths, myocardial infarction
and stroke) in 12 months.
56 Clusters including 1.680 consecutive high cardiovascular risk
patients
Concealed Randomization
Multifaceted Quality
Improvement Intervention
(n= 28 clusters)
Routine Practice
(n= 28 clusters)
ITT
ITT
Primary Endpoint: Adherence to lipid lowering agents, anti platelets
and ACE inhibitors
Secondary Endpoints: clinical events composite score
14
BRIDGE-CV Intervention
Simulation Based
Training
Case
Manager
Educational Material
Decision Support System
Flow chart
Pocket Guidelines
15