1、Antithombosis in Primary Prevention Where do we stand/where are we goingDr. Carlos Brotons,Primary prevention trials with Aspirin:review of the Evidence,1988 British Doctors Trial 1998 Thrombosis Prevention Trial Hypertension Optimal Treatment (HOT) Study 1989 Physicians Health Study Primary Prevent
2、ion Project 2005 Womens Health Study,Meta-Analysis of Data from the Six Primary Prevention Trials of Cardiovascular Events Using Aspirin,Alfred A. Bartolucci, PhD*, and George Howard, DrPH,Am J Cardiol 2006; 98:746,Aspirin in the primary prevention of cardiovascular (CV) events,BDT, British Doctors
3、Trial; HOT, Hypertension Optimal Treatment; PHS, Physicians Health Study; PPP, Primary Prevention Project; qod, every other day; TPT, Thrombosis Prevention Trial; WHS, Womens Health Study. 1. Peto R, et al. BMJ 1988;296:3136; 2. Physicians Health Study. N Engl J Med 1989;321:18258; 3. Hansson L, et
4、al. Lancet 1998;351:175562. 4. The Medical Research Councils General Practice Research Framework. Lancet 1998;351: 23341; 5. de Gaetano G, et al. Lancet 2001;357:8995. 6. Ridker PM, et al. N Engl J Med 2005;352:1293304.,Primary findings (total CV events) from the six key trials,Odds Ratio and 95% CI
5、,0.5,1,2,ASPIRIN,CONTROL/ PLACEBO,Peto R, et al. BMJ 1988;296:3136; Physicians Health Study. N Engl J Med 1989;321:18258; Manson JE, et al. JAMA 1991;266:5217; Hansson L, et al. Lancet 1998;351:175562. The Medical Research Councils General Practice Research Framework. Lancet 1998;351:23341; de Gaeta
6、no G. Lancet 2001;357:8995. Ridker PM, et al. N Engl J Med 2005;352:1293304.,Results of the Meta-analysis regarding the prevention of coronary heart disease,The overall risk reduction of total CHD (nonfatal and fatal MI and death due to CHD) was in favor of aspirin therapy (odds ratio of 0.77),BDT,P
7、HS,HOT,PPP,WHS,Combined,TPT,0.5 1 2,Favours aspirin Favours placebo,Odds ratio and 95% CI,CHD, coronary heart disease Bartolucci AA, et al. Am J Cardiol 2006;98:74650. .,Bartolucci AA, et al. Am J Cardiol 2006;98:74650.,Meta-analysis of six primary prevention trials showed no differences for the pre
8、vention of stroke (OR 0.945; p=0.336),Results of the Meta-analysis regarding the prevention of the stroke,BDT,TPT,HOT,PPP,Combined,WHS,PHS,0.5 1 2,Odds ratio and 95% CI,Favours aspirin Favours placebo,Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men,A Sex-Specific Meta-an
9、alysis of Randomized Controlled Trials,Berger JS. JAMA 2006;306,32%,Effect of Aspirin Treatment on the Primary Preventionof Myocardial Infarction,17%,Effect of Aspirin Treatment on the Primary Prevention ofStroke, Ischemic Stroke and Hemorrhagic Stroke,24%,Effect of Aspirin Treatment on the Primary
10、Prevention of Ischemic Stroke,32%,28%,Effect of Aspirin Treatment on Major Bleeding,Absolute risk is very low: less than 1%,Reduction in serious vascular events with antiplatelet therapy in high-risk patients 287 studies, 135.000 patients,Category % odds reduction Acute MI Acute stroke Prior MI Prio
11、r stroke/transient ischemic attack Other high risk: Coronary artery disease (e.g., unstable angina, heart failure) Peripheral arterial disease (e.g., intermittent claudication) High risk of embolism (e.g., atrial fibrillation) Other (e.g., diabetes mellitus) All trials 22% 2,1.0,0.5,0.0,1.5,2.0,Cont
12、rol,Antiplatelet,MI, myocardial infarction Antithrombotic Trialists Collaboration. BMJ. 2002; 324:7186,Reduction in serious vascular events with antiplatelet therapy in high-risk patients 287 studies, 135.000 patients,*Antithrombotic Trialists Collaboration. BMJ 2002;324:71,75-150 mg aspirin daily i
13、s considered routinely for all such patients at higher risk of vascular events (more than 2% a year) irrespective of whether they have already a major vascular event,Major CV events Relative risk reduction vs absolute risk reduction,HIGH RISK PATIENTS*,LOW RISK PATIENTS*,RRR2215,ARR25 per 1000 treat
14、ed NNT 40 3 per 1000 treated NNT 333,*Antithrombotic Trialists Collaboration. BMJ 2002;324:71 * Meta-analysis of RCT. JAMA 2006;296,Major CV events Relative risk reduction vs absolute risk reduction,ALTHOUGH RELATIVE BENEFITS APPEARED BROADLY SIMILAR IN HIGH RISK AND LOW RISK PATIENTS THE ABSOLUTE B
15、ENEFITS IN LOW RISK PATIENTS IS VERY SMALL.,*Antithrombotic Trialists Collaboration. BMJ 2002;324:71 * Meta-analysis of RCT. JAMA 2006;296,Guidelines support the use of aspirin for primary prevention of CV events,European guidelines on CVD prevention in clinical practice (2007) American Heart Associ
16、ation (AHA) http:/www.americanheart.org/ Evidence-based AHA guidelines for CVD prevention in women (2007 update). The guide to clinical preventive services 2008: recommendations of the U.S. Preventive Services Task Force (USPSTF).American College of Chest Physicians E-B Clinical Practice Guidelines-
17、 Antiplatelet Drugs (2008),European guidelines on CVD prevention in clinical practice,Aspirin (75 mg daily) can be considered in all patients with CVD, and in those at high risk of developing CVD (SCORE 10% over 10 years) once blood pressure has been controlled (as closely as possible to the goal of
18、 less than 140/90 mmHg)In lower risk individuals a small absolute vascular benefit by aspirin maybe offset by the slightly greater absolute risk of bleeding complications,EJCPR 2007;vol 14(suppl 2):S1-S113,American Heart Association (AHA) Guidelines,Benefits of reducing CV risk outweigh these risks
19、in most patients with higher coronary risk Doses of aspirin 75160 mg per day are as effective as higher doses Consider aspirin 75160 mg per day for people at higher risk (especially those with a 10-year CHD risk of 10 percent or greater),Circulation 2002;106:338-391,AHA guidelines for CVD prevention
20、 in women (2007 update),Aspirin: high-risk Any vascular disease, end-stage or chronic renal disease, diabetes mellitus, and 10-year Framingham risk 20% Aspirin therapy 75 to 325 mg per day should be used in high-risk women unless contraindicated (Class I, Level A),Circulation 2007;115:1481-1501,Guid
21、e to clinical preventive services 2008: recommendations from USPSTF,USPSTF strongly recommends that clinicians discuss aspirin chemoprevention with adults who are at increased risk for CHD Discussions with patients should address both the potential benefits and harms of aspirin therapy Grade: A Reco
22、mmendation,Guide to clinical preventive services 2008: recommendations from USPSTF,Baseline risk for CHD over 5 years: 1% Total mortality: no effect CHD events: 14 avoided Hemorrhagic strokes: 02 caused Major gastrointestinal bleeding events: 24 caused,Guide to clinical preventive services 2008: rec
23、ommendations from USPSTF,Baseline risk for CHD over 5 years: 3% Total mortality: no effect CHD events: 412 avoided Hemorrhagic strokes: 02 caused Major gastrointestinal bleeding events: 24 caused,Guide to clinical preventive services 2008: recommendations from USPSTF,Baseline risk for CHD over 5 yea
24、rs: 5% Total mortality: no effect CHD events: 620 avoided Hemorrhagic strokes: 02 caused Major gastrointestinal bleeding events: 24 caused,Who should be treated with aspirin?,The decision to use aspirin should be based on a balance of the risks and benefits for each person taking into account their
25、absolute risk for CHD or CVD.Patients with established CVD or very high risk patients should be treated with aspirin unless contraindicated.Before starting treatment with aspirin always consider risks factors for GI bleeding such as age and concomitant use of NSAIDS.An unanswered question In primary
26、 prevention is whether the benefits of daily aspirin outweights the harms in specific populations (such as those with moderate risk of CHD),Antithombosis in Primary Prevention Where are we going ? Ongoing trials to assess the benefit:risk profile of low-dose aspirin in the prevention of first CV eve
27、nts,The ARRIVE Study (Aspirin to Reduce Risk of Initial Vascular Events),Rationale,ARRIVE will expand the already existing, strong body of evidence supporting aspirin for primary prevention of CVD eventsARRIVE was designed to demonstrate the efficacy and safety of low-dose aspirin in a moderate-risk
28、 population,CHD risk continuum,ARRIVE,# of MIs prevented (Per 1,000 patients treated for 10 years),CHD 10-year Risk,BENEFIT RISK,BENEFIT RISK,BENEFIT RISK,Overall CHD, Stroke, and CV Death,Risk Estimates by Age and Gender (All Countries),Overview of the ARRIVE Trial,Sample Size: 12,000 patients (6,0
29、00 per group) will be enrolled Duration of Study: approximately 5 years Study Locations: More than 400 trial sites across Germany, Ireland, Italy, Poland, Spain, UK, USA Gender Distribution: 70% male/30% female Intervention: 1:1 daily aspirin (100 mg) or placebo,Study design,Aspirin daily (100 mg) (
30、n6,000),Placebo 1 tablet daily (n6,000),12-month visit,R=Randomization; *First occurrence of composite outcome of MI, stroke, or cardiovascular death; +Telephone contact,Patients (n=12,000) at moderate risk of CVD events,R,Double-blind treatment up to 1,488 primary efficacy events*,3-month visit,Vis
31、its every 12 months,+,+,+,+,+,+,+,+,+,+,+,+,+,+,ARRIVE Trial: Inclusion Criteria,Males aged 50 to 75 years with 2 or 3 CV risk factorsFemales aged 60 and above with 3 or more CV risks factors,ARRIVE Trial: Primary efficacy endpoint,Composite outcome consisting of the first ocurrence of cardiovascula
32、r death, MI, or stroke.,Summary of the ARRIVE Trial,ARRIVE is one of the largest aspirin studies ever conducted in a population at moderate risk of initial cardiovascular and cerebrovascular events ARRIVE creates additional opportunities to communicate the positive benefits of aspirin and address the problem of underutilization,
