1. Cardiovascular Epidemiology and Epidemiological Modelling
Key facts regarding CVD treatments: Using the evidence base in modelling
Martin O’Flaherty
Simon Capewell
Division of Public Health
University of Liverpool

2. A Simplified model of the Clinical phase of Atherosclerosis
Sudden Death
At risk
Acute Myocardial Infarction
Death
Heart Failure
MI Survivors
Unstable Angina
Chronic
Angina
Stroke

3. Key patients groups Acute Coronary Syndromes Stable Angina
Heart Failure
Stroke
Peripheral Arterial disease

4. Strategies to Manage CVD Disease
Aims:
Prevent clinical disease
Postpone disease progression
Decrease mortality
Increase Quality of Life

5. Acute Coronary Syndromes
Complex situation:
Definitions keep changing for clinical purposes.
Epidemiological definitions:
Circulation Nov 18;108(20):2543-9
EuroCISS:
Groups (Clinical)
Acute Myocardial infarction
STEMI (ST elevation Myocardial Infarction)
NSTEMI (Non ST elevation Myocardial infarction
Unstable angina

6. Acute myocardial infarction
Atherosclerotic plaque rupture leading to a sudden occlusion of a coronary artery
Myocardial muscle loss.
Host of complications:
Electrical: arryhtmias
Mechanical: heart failure and cardiogenic shoc
Therapy:
Type of AMI (STEMI vs NSTEMI) is critical to guide decisions
Decrease size of infarct
Treat complications
Stabilize atherosclerotic plaque to prevent further ischemic events
Efficacy outcomes:
Rates of major cardiovascular events:
Death
Recurrent AMI
Refractory ischaemia
Stroke.
Safety outcomes:
Rates of major bleeding

7. Angiotensin Converting Enzyme inhibitors SR
Interventions
Effect on mortality
Type of evidence
Angiotensin Converting Enzyme inhibitors SR
Aspirin
Beta Blockers
STEMI: Primary percutaneous coronary intervention (PCI)
STEMI: Thrombolysis 7%
15% 4%
32%
31%
Ongoing debate
PCI vs. thrombolysis

8. Unstable Angina Therapy:
Atherosclerotic plaque unstable, producing inflammatory and thrombotic phenomena causing myocardial ischemia but not myocardial muscle death.
Definition:
New symptoms
Recent change in the stable anginal symptoms pattern
No evidence of myocardial necrosis.
Therapy:
Avoid progression to AMI
Stabilize atherosclerotic plaque to avoid progression of ischemia (eg: to AMI)
Revascularization strategies based on risk of future events and anatomy
Efficacy outcomes:
Rates of major cardiovascular events:
Death
AMI
Refractory ischaemia
Re admission to hospital
Safety outcomes:
Rates of major bleeding

9. gpIIb/IIIa inhibitors/Clopidogrel
Interventions
Effect on mortality
Type of evidence
Aspirin and Heparins SR
gpIIb/IIIa inhibitors/Clopidogrel
Beta Blockers
Percutaneous coronary intervention (PCI)
CABG
33% 9%
32%
32%
43%

10. Chronic Angina Therapy:
Progressive occlusion by an atherosclerotic plaque, causing myocardial ischemia.
Definition:
Clinical definition based on anginal symptoms, pattern and duration
Several validated questionnaires (Rose questionnaire)
Therapy:
Avoid ischemic events (secondary prevention)
Symptom relief
Efficacy outcomes:
Rates of major cardiovascular events:
Death
AMI/UA
Symptoms and Quality of Life
Safety outcomes:
Rates of major bleeding

11. Secondary Prevention in CVD patients
Who:
Every patient with Clinical CHD (Survivors of ACS, Chronic Angina, CHD related heart failure and) and Stroke
Aspirin/Clopidogrel
Anticoagulants
ACEI/ARIIB
Beta blockers (stroke: may not be indicated)
Statins
BP reduction
Smoking cessation
Rehabilitation

12. CABG Compared to Medical treatment: Has an effect on mortality.
Benefit changes with:
Extent of coronary artery involvement
Ventricular function
Yusuf et al. Lancet 1994; 344:

13. PCI Compared to Medical treatment It has no mortality benefit
It produces symptom relief.
Bucher et al. BMJ 2000; 321:

14. Drug eluting stents
Boden et al. NEJM 356 (15): 1503

15. Heart Failure Therapy:
Progressive loss of the pump function of the heart
Definition:
Clinical syndrome + a measure of ventricular function. Some biomarkers are beeing increasingly used in clinical practice.
Therapy:
Decrease mortality from
Progressive heart failure
Sudden death
Symptom relief
Resource use control
Efficacy outcomes:
Rates of major cardiovascular events:
Death
Symptoms and Quality of Life
Proxy measures of ventricular function

16. Available treatments for Heart Failure
Rehab
ACEI/ARII b
Aspirin?
Beta-blockers
Implantable Cardio Defibrillators
Spironolactone
Anticoagulants ?
Amiodarone?
Statins?

17. Statins in Heart Failure
Current Debate:
Physiopathological thinking suggests a role
Role of statins in PostMI and CA
Observational evidence suggest an effect
Clinical trials:
CORONA : no effect
GISSI: expecting results

18. Statins in heart failure
CHD related
Non CHD related
J Am Coll Cardiol Jan 29;51(4):415-26

19. Key issues when modelling interventions
Mortality benefit or Quality of Life?
Which patients are eligible?
Current guidelines

20. Key issues when modelling interventions
Efficacy vs effectiveness:
RCT and SR usually better than real practice
Uptake: those not receiving the drug do not benefit from it.
Many interventions acting on the same individuals:
Estimation of a common effect: The Mant-Hicks approach

21. Summary Patients groups Strategies
High quality information on efficacy
AMI
PCI vs thrombolysis
Chronic Angina
CABG vs PCI vs Medical Management
Heart Failure
Statins
Key facts in modelling interventions