一级预防的抗栓现状与未来

Antithombosis in Primary Prevention Where do we stand/where are we going Dr. Carlos Brotons Primary prevention trials with Aspirin: review of the Evidence 1988 British Doctors Trial 1998 Thrombosis Prevention Trial 1998 Hypertension Optimal Treatment (HOT) Study 1999 1989 Physicians Health Study 2001 Primary Prevention 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 Trial Patient population Age range (years) Aspirin dosage BDT (1988)1 Apparently healthy male physicians (n=5,139) 5078 500mg/day PHS (1989)2 Apparently healthy male physicians (n=22,071) 4084 325mg qod HOT study (1998)3 Men and women with DBP 100115mmHg (n=18,790) 5080 75mg/day TPT (1998)4 Men at high risk of heart disease (n=5,499) 4569 75mg/day PPP (2001)5 Men and women with 1 major CV risk factor (n=4,495) 5080+ 100mg/day WHS (2005)6 Apparently healthy women (n=39,876) 45 100mg qod BDT, British Doctors 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 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 Study Name Risk Aspirin Control/ Placebo Odds BDT Low 260/3429 127/1710 1.023 0.842 PHS Low 292/11037 390/11034 0.769 0.001 TPT High 208/1268 250/1272 0.741 0.003 HOT Low 243/9399 290/9391 0.824 0.033 PPP Low 46/2226 65/2269 0.546 0.006 WHS Low 539/19934 585/19942 0.982 0.780 TOTAL 1588/47293 1707/45618 0.869 10% over 10 years) once blood pressure has been controlled (as closely as possible to the goal of 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 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 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 Guide 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 Recommendation 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: recommendations 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 years: 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 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 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 events 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 events ARRIVE was designed to demonstrate the efficacy and safety of low-dose aspirin in a moderate-risk 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 Mean 10-Year Risk (%) CHD (PROCAM and Framingham) STROKE (Framingham) CV Death (SCORE) Total (CVD) High-risk countries 15.8% 9.1% 5.1% 30.0% Risk Estimates by Age and Gender (All Countries) Low-risk countries 8.5% 9.1% 2.75% 20.3% Overall 12.9% 9.1% 4.1% 26.1% Overview of the ARRIVE Trial Sample Size: 12,000 patients (6,000 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) (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