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

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

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

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

Acute Coronary Syndromes Complex situation: Definitions keep changing for clinical purposes. Epidemiological definitions: Circulation. 2003 Nov 18;108(20):2543-9 EuroCISS: http://www.cuore.iss.it/eurociss Groups (Clinical) Acute Myocardial infarction STEMI (ST elevation Myocardial Infarction) NSTEMI (Non ST elevation Myocardial infarction Unstable angina

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

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

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

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%

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

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

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: 563-70.

PCI Compared to Medical treatment It has no mortality benefit It produces symptom relief. Bucher et al. BMJ 2000; 321: 73- 7.

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

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

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

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

Statins in heart failure CHD related Non CHD related J Am Coll Cardiol. 2008 Jan 29;51(4):415-26

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

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

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