二级预防的研究组织的前提

STROKE: SECONDARY PREVENTION THE WHO PREMISE STUDY MARGARITA E. DAZ CENTRE FOR ACADEMIC MEDICAL RESEARCH Montevideo Uruguay DEFINITION Stroke is defined as an episode of focal or global neurological deficit of rapid onset and lasting over 24 hours or leading to death, with no cause apparent other than a vascular one. IS STROKE A FREQUENT PHENOMENON? WORLDWIDE PERCENTAGES OF DEATHS Stroke and other leading causes 2002 Source Mackay, J, Mensah, G. The Atlas of Heart Disease and Stroke.WHO-CDC, 2004. Total number of Deaths: 57 million l Stroke is the 3rd most common cause of death l 50 million have suffered a stroke l 5 million die each year because of a stroke WORLDWIDE IMPACT OF STROKE WORLDWIDE CONSEQUENCES OF STROKE l Almost 33 % of those who present a stroke die in 3 weeks l 50 % of survivors are left with physical and/or mental disability l 20 % of survivors suffer another stroke within 5 years PREVALENCE OF RECURRENT STROKE Hier DB et al Stroke 1991; 22: 155-161. Onset 6 months 1 year 0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 18 months 2 years Cumulative distribution Time after first stroke WHO PREMISE Study of secondary prevention of stroke Causes of stroke and its established risk factors Non-modifiable and modifiable risk factors Results of the WHO PREMISE Study Prevalence of the most important risk factors Use of medication from the WHO PREMISE Study By socio-demographic characteristics According to risk factors By clinical characteristics Predictors for the use of medication Perspectives of pharmacological intervention Clinical trials with universal treatment Specific treatment according to diagnosis: isquemic/hemorrhaegic stroke Compliance OBJECTIVES OF THE WHO PREMISE STUDY PHASE 1 l To assess current practice patterns related to secondary prevention of coronary heart disease and cerebrovascular disease (CeVD) in primary, secondary and tertiary health care settings l Learn about patient behaviour and compliance in the 3 years after an event l Implement strategies to strengthen the health care system with interventions based in primary care and community based action CRUDE PREVALENCE OF STROKE IN THE PARTICIPATING COUNTRIES IN THE WHO-PREMISE STUDY n=10 855 Population In Millions (2002) Sample size (n) Prevalence of stroke (%) Brazil 180 996 16.1 Egypt 71 996 21.3 India 1 000 1 013 8.0 Indonesia 234 999 44.3 Iran 68 916 4.4 Pakistan 156 1 007 13.2 Russia 143 993 7.5 Sri Lanka 19 1 038 24.0 Tunisia 9 999 5.5 Turkey 68 1 000 6.0 Uruguay 3 898 25.0 WHO PREMISE Study of secondary prevention of stroke Causes of stroke and its established risk factors Non-modifiable and modifiable risk factors Results of the WHO PREMISE Study Prevalence of the most important risk factors Use of medication from the WHO PREMISE Study By socio-demographic characteristics According to risk factors By clinical characteristics Predictors for the use of medication Perspectives of pharmacological intervention Clinical trials with universal treatment Specific treatment according to diagnosis: isquemic/hemorrhaegic stroke Compliance NON-MODIFIABLE RISK FACTORS FOR STROKE l Age l sex l Heredity l Ethnicity l Previous stroke ESTABILISHED MODIFIABLE RISK FACTORS FOR STROKE Hypertension Chronic renal insufficiency Carotid stenosis Smoking Heavy alcohol consumption Physical inactivity Dyslipidaemia Diabetes mellitus CANDIDATE RISK FACTORS FOR STROKE Migraine Oral contraceptives Sleep apnoea Cocaine and amphetamines Certain infections Elevated homocysteine MODIFIABLE CARDIAC RISK FACTORS FOR STROKE Coronary heart disease Myocardial infarction Congestive heart failure l Left ventricular disfunction/ mural thrombus l Mitral stenosis Atrial fibrillation RATES of MORTALITY for CEREBROVASCULAR DISEASE by age and sex group, Canada Health Canada, 1999 PREDICTORS OF DEATH FROM STROKE IN ITALY Percentage increased risk of death from stroke in people aged 65 years and above, 2001 Number of deaths from Stroke in 2002 : 69.075 Source Mackay, J, Mensah, G. The Atlas of Heart Disease and Stroke.WHO-CDC, 2004. WHO PREMISE Study of secondary prevention of stroke Causes of stroke and its established risk factors Non-modifiable and modifiable risk factors Results of the WHO-PREMISE Study Prevalence of the most important risk factors Use of medication from the WHO PREMISE Study By socio-demographic characteristics According to risk factors By clinical characteristics Predictors for the use of medication Perspectives of pharmacological intervention Clinical trials with universal treatment Specific treatment according to diagnosis: isquemic / hemorrhaegic stroke Compliance TOTAL NUMBER OF PARTICIPANTS OF CORONARY HEART DISEASE (CHD) AND STROKE IN THE WHO-PREMISE STUDY AGE GROUPS FOR MALES AND FEMALES TOTAL NUMBER OF PARTICIPANTS OF CHD AND STROKE BY AGE AND SEX IN THE WHO-PREMISE STUDY CeVD: Cerebrovascular disease REPORTED HISTORY OF RISK FACTORS IN PERCENTAGES AMONG ALL CVD PATIENTS WHO-PREMISE STUDY HBP: High blood pressure - HBS High blood sugar - HC High blood cholesterol CLUSTERING OF RISK FACTORS IN PERCENTAGES AMONG ALL CVD PATIENTS WHO-PREMISE STUDY 0 FR 1 FR 2 FR 3 FR 4 FR LYFESTYLE CHANGES HAVE A MAJOR IMPACT ON SECONDARY PREVENTON ANTIHYPERTENSIVE TREATMENT IS 510 TIMES MORE SUCCESSFUL IN ELDERLY PATIENTS THAN IN MIDDLE-AGED PATIENTS WITH MILD HYPERTENSION (1000 pts/5 years) expected prevented expected prevented Mild Hypertension Events hypertension in the elderly Cardiovascular 15 4-5 120 40 deaths Strokes 15 10 123 49 Coronary events 30 2-3 97 14 Holzgreve and Middeke, 1994 WHO PREMISE Study of secondary prevention of stroke Causes of stroke and its established risk factors Non-modifiable and modifiable risk factors Results of the WHO-PREMISE Study Prevalence of the most important risk factors Use of medication in the WHO PREMISE Study By socio-demographic characteristics According to risk factors By clinical characteristics Predictors for the use of medication Perspectives of pharmacological intervention Clinical trials with universal treatment Specific treatment according to diagnosis: isquemic/hemorrhaegic stroke Compliance PERCENTAGE OF PATIENTS WITH STROKE TAKING MEDICATIONS IN ALL CeVD PATIENTS n =10 855 WHO-PREMISE STUDY USE OF MEDICATIONS IN PERCENTAGES BY REPORTED RISK FACTORS AMONG ALL CVD PATIENTS ASPIRIN (%) BLOCKERS (%) ACE inhibitor (%) STATINS (%) HBP n= 6 730 86.6 54.9 53.6 24.1 HBC n= 4 012 86.1 55.9 50.7 40.2 HBS n= 3 133 87.4 50.8 47.9 25.4 Current Smokers n= 1 245 89.2 58.5 48.7 22.3 HBP: High blood pressure HBC: High blood cholesterol HBS: High blood sugar WHO-PREMISE STUDY USE OF MEDICATIONS IN PERCENTAGES BY SOCIO-DEMOGRAPHIC CHARACTERISTICS AMONG ALL CVD PATIENTS ASPIRIN (%) BLOCKERS (%) ACE inhibitor (%) STATINS (%) GENDER Males 87 54 48 26 Females 47 51 47 21 p 60 years 85 51 50 21 p 0.94 0.03 75 years No or yes Warfarin Risk factors: History of cerebrovascular disease or TIA, left ventricular dysfunction , valvular hearth disease, congestive heart failure, systolic blood pressure 160 mmHg. Source: EAFT (European Atrial Fibrillation Trial) Study Group STUDY OF DRUG COMPLIANCE IN SECONDARY PREVENTION OF STROKE - TIANTAN HOSPITAL PATIENTS OF CAPITAL UNIVERSITY OF MEDICAL SCIENCES, BEIJING, CHINA. Objective: Identify rate of Compliance for secondary prevention according to the prevalence of risk factors Telephone interview of 296 consecutive patients entering the Neurology Department October-02 to April-03 Treatment Compliance: Hypertension: 78 % Diabetes: 80 % Hyperlipidoemia: 48 % Antithrombotic drugs: 35 % + Compliance: Medical insurance and free medical care OD 2.12 (95 % CI: 1.17-3.82) - Compliance: Use of antithrombotic drugs other than aspirin OD 0.35 (95 % CI: 0.15-0.81) and lower living ability (62.5 13.3 p0.001) Comments: Incorrect discontinuation of drugs or change and reduction of dosage reflect a need of clear guidelines for patients Source: Wu D, Ma RH, Wang YL, Wang YJ. Zhonghua Nei Ke Za Zhi. 2005. LOOKING INTO PERSPECTIVE l Secondary prevention of stroke l Primary prevention of stroke l Secondary prevention of myocardial infarction l New mechanisms of the physiopathology and pathogenesis of the recurrent stroke l New drugs and known drugs with unknown mechanisms Considerations of available information on the following items permit to outline high-priority research questions on the secondary prevention of stroke: WHAT NEEDS TO BE KNOWN ABOUT THE CONTROL OF HYPERTENSION Lowering blood pressure has proved to be the best therapeutic tool to prevent a stroke. Primary prevention has demonstrated that Amlodipine or slow release calcium antagonist are, together with diuretics useful and better than beta- blockers and ACE inhibitors (Lisinopril in the ALLHAT study) once an equal hipotensive effect is obtain, is this the case for secondary prevention? ACE inhibitors (Perindopril + Indapamide 2.5) have proven to be effective in secondary prevention of stroke, are they more effective than slow release calcium antagonists or diuretics? Angiotensin II antagonists and Aldosterone antagonists need to be tried and compared with drugs that have already shown a benefit at least in primary prevention of stroke. HOW TO OPTIMIZE ANTITHROMBOTIC THERAPY - LIMITED TO PATIENTS WHOSE FIRST STROKE WAS UNEQUIVOCALLY ISQUAEMIC Patients with atrial fibrillation and/or cardiac emboli have proven to be better treated with Warfarin. The data of primary and secondary prevention of myocardial infarction has shown that Aspirin (low dose) and Clopidogrel are the best combination, and better than a single drug. Aspirin has not proven to be as good for prevention of brain damage as it has at heart level. Is the combination with Clopidogrel an option in this case? Are they applicable for secondary stroke prevention patients? It is in order to investigate whether antithrombins (eg.: Ximelagatran) merits dedicated research in patients with and without atrial fibrillation. ROLE OF CHOLESTEROL LOWERING DRUGS IN SECONDARY PREVENTION OF STROKE Statins have shown to be effective in primary prevention of stroke, though their therapeutic mechanism of action which apparently exceeds the one obtained with the inhibition of the HMG Ca reductase in the initial stroke - is still unknown. Are statins useful in secondary prevention? Do they do so through the same or other mechanisms?