Antithombosis in Primary Prevention Where do we stand/where are we goingDr. Carlos BrotonsPrimary prevention trials with Aspirin:review of the Evidence1988 British Doctors Trial1998 Thrombosis Prevention Trial 1998 Hypertension Optimal Treatment (HOT) Study1999 1989 Physicians Health Study2001 Primary Prevention Project2005 Womens Health StudyMeta-Analysis of Data from the Six Primary Prevention Trials of Cardiovascular Events Using AspirinAlfred A. Bartolucci, PhD*, and George Howard, DrPHAm J Cardiol 2006; 98:746Aspirin in the primary prevention of cardiovascular (CV) eventsTrialPatient populationAge range (years)Aspirin dosage BDT (1988)1Apparently healthy male physicians (n=5,139)5078 500mg/dayPHS (1989)2Apparently healthy male physicians (n=22,071)4084 325mg qodHOT study (1998)3Men and women with DBP 100115mmHg (n=18,790)5080 75mg/dayTPT (1998)4Men at high risk of heart disease (n=5,499)456975mg/dayPPP (2001)5Men and women with 1 major CV risk factor (n=4,495)5080+100mg/dayWHS (2005)6Apparently healthy women (n=39,876) 45100mg qodBDT, 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 trialsStudy NameRisk AspirinControl/PlaceboOddsBDTLow260/3429127/17101.0230.842PHSLow292/11037390/110340.7690.001TPTHigh208/1268250/12720.7410.003HOTLow243/9399290/93910.8240.033PPPLow46/222665/22690.5460.006WHSLow539/19934585/199420.9820.780TOTAL1588/472931707/456180.86910% 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 complicationsEJCPR 2007;vol 14(suppl 2):S1-S113American 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;106:338-391AHA 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;115:1481-1501Guide 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 RecommendationGuide 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 causedGuide 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 causedGuide 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 causedWho 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 eventsThe 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 designe