## Recommendations and Rationale

# Aspirin for the Primary Prevention of Cardiovascular Events

### U.S. Preventive Services Task Force (USPSTF)

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This statement summarizes the current U.S. Preventive Services Task Force (USPSTF) recommendation on aspirin for the primary prevention of cardiovascular events and the supporting scientific evidence, and updates the 1995 recommendation contained in the *Guide to Clinical Preventive Services*, Second Edition1.

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| Summary of Recommendation- **The U.S. Preventive Services Task Force (USPSTF) strongly recommends that clinicians discuss aspirin chemoprevention with adults who are at increased risk for coronary heart disease (CHD) (*go to  Clinical Considerations*). Discussions with patients should address both the potential benefits and harms of aspirin therapy.**  **Rating: A recommendation**.  *Rationale:* The USPSTF found good evidence that aspirin decreases the incidence of coronary heart disease in adults who are at increased risk for heart disease. They also found good evidence that aspirin increases the incidence of gastrointestinal bleeding and fair evidence that aspirin increases the incidence of hemorrhagic strokes. The USPSTF concluded that the balance of benefits and harms is most favorable in patients at high risk of CHD (5-year risk of greater than or equal to 3 percent) but is also influenced by patient preferences. |
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## Contents

 Clinical Considerations Scientific Evidence Recommendations of Others References and Notes Members of the Task Force Contact the Task Force Available Products

| **Task Force Ratings**Strength of Recommendations and Quality of Evidence |
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## Clinical Considerations

- Decisions about aspirin therapy should take into account overall risk for coronary heart disease.  Risk assessment should include asking about the presence and severity of the following risk factors: age, sex, diabetes, elevated total cholesterol levels, low levels of high-density lipoprotein (HDL) cholesterol, elevated blood pressure, family history (in younger adults), and smoking.  Tools that incorporate specific information on multiple risk factors provide more accurate estimation of cardiovascular risk than categorizations based simply on counting the numbers of risk factors ( http://www.intmed.mcw.edu/clincalc/heartrisk.html ). 2
- Men older than 40 years, postmenopausal women, and younger people with risk factors for coronary heart disease (eg, hypertension, diabetes, or smoking) are at increased risk for heart disease and may wish to consider aspirin therapy.   Table 1  shows how estimates of the type and magnitude of benefits and harms associated with aspirin therapy vary with an individual's underlying risk for coronary heart disease. Although balance of benefits and harms is most favorable in high-risk people (5-year risk greater than 3 percent), some people at lower risk may consider the potential benefits of aspirin to be sufficient to outweigh the potential harms.
- Discussions about aspirin therapy should focus on potential coronary heart disease benefits, such as prevention of myocardial infarction, and potential harms, such as gastrointestinal and intracranial bleeding. Discussions should take into account individual preferences and risk aversions concerning myocardial infarction, stroke, and gastrointestinal bleeding.
- Although the optimal timing and frequency of discussions related to aspirin therapy are unknown, reasonable options include every 5 years in middle-aged and older people or when other cardiovascular risk factors are detected.
- Most participants in the primary prevention trials of aspirin therapy have been men between 40 and 75 years of age.  Current estimates of benefits and harms may not be as reliable for women and older men.
- Although older patients may derive greater benefits because they are at higher risk for CHD and stroke, their risk for bleeding may be higher.
- Uncontrolled hypertension may attenuate the benefits of aspirin in reducing CHD.
- The optimum dose of aspirin for chemoprevention is not known.  Primary and secondary prevention trials have demonstrated benefits with a variety of regimens, including 75 mg per day, 100 mg per day, and 325 mg every other day.  Doses of approximately 75 mg per day appear as effective as higher doses; whether doses below 75 mg per day are effective has not been established.  Enteric-coated or buffered preparations do not clearly reduce adverse gastrointestinal effects of aspirin.  Uncontrolled hypertension and concomitant use of other nonsteroidal anti-inflammatory agents or anticoagulants increase risk for serious bleeding.

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## Scientific Evidence

### Epidemiology and Clinical Background

Cardiovascular disease, including ischemic coronary heart disease, stroke, and peripheral vascular disease, is the leading cause of death in the United States.3 Yearly, over 1 million Americans experience new or recurrent myocardial infarction or fatal coronary heart disease.  Most events occur in older people and those with recognized risk factors for cardiovascular disease, including high cholesterol, high blood pressure, diabetes, or a history of smoking.

The early-documented and clear success of aspirin in preventing further clinical disease in some patients with known heart disease (secondary prevention) raised interest in aspirin as a potential primary preventive intervention in men and women without known heart disease.4  Two early randomized trials of aspirin had conflicting results, however, and lacked sufficient power to estimate major harms, such as gastrointestinal bleeding and hemorrhagic stroke.5,6  Thus, the role of aspirin in primary prevention has remained controversial.  The new USPSTF recommendation incorporates additional data from three recent trials and provides more reliable estimates of both benefits and harms of aspirin in patients without known heart disease.

### Efficacy of Chemoprevention

Five trials have examined the effects of daily or every-other-day aspirin for the primary prevention of cardiovascular events over periods of 4 to 7 years.5-9 Most participants were men older than 50 years.  Meta-analysis of pooled data from all of the studies showed that aspirin therapy reduced the risk for CHD by 28 percent (summary odds ratio [OR], 0.72; 95 percent CI, 0.60 to 0.87). Summary estimates showed no significant effects of aspirin on total mortality (OR, 0.93; 95 percent CI, 0.84 to 1.02) and stroke (OR, 1.02; 95 percent CI, 0.85 to 1.23).

### Harms of Chemoprevention

These five primary prevention trials, and a larger number of randomized controlled trials (RCTs) of secondary prevention that enrolled patients with heart disease or stroke, demonstrate that aspirin increases rates of gastrointestinal bleeding.  Estimated rates of major gastrointestinal bleeding episodes are approximately 2 to 4 per 1,000 middle-aged individuals (4 to 12 for older individuals) given aspirin for 5 years.10-12

These controlled trials in primary and secondary prevention settings also suggest that aspirin increases rates of hemorrhagic strokes by a small amount (0-2 per 1,000 individuals given aspirin for 5 years).5-7  Such estimates are less reliable than those of gastrointestinal bleeding because few strokes were reported in the trials.

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## Recommendations of Others

In 1994, the Canadian Task Force on Preventive Health Care concluded that the evidence was not strong enough to recommend for or against use of aspirin for primary prevention of heart disease in men or women and recommended that physicians and patients balance the reduced rate of nonfatal myocardial infarction against potential adverse effects.13  In 2000, the American Diabetes Association recommended that clinicians consider aspirin for primary prevention of heart disease in diabetic patients who are older than 30 years or have risk factors for cardiovascular disease and no contraindications to aspirin therapy.14  In 1997, the American Heart Association concluded that aspirin may be warranted for patients at high risk of myocardial infarction but that health care providers must consider a patient's particular cardiovascular risk profile, the demonstrated benefits of aspirin on reducing risk for a first myocardial infarction, and known as well an unknown side effects of aspirin.15

In 1998, the European Society of Cardiology recommended low-dose aspirin (75 mg) for patients with well-controlled hypertension and men at "particularly" high risk for coronary heart disease, but not for all individuals at high risk.16

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## References

-  U.S. Preventive Services Task Force.  Guide to Clinical Preventive Services.  2nd edition.  Washington, DC: Office of Disease Prevention and Health Promotion, U.S. Government Printing Office; 1996.
-  Wilson PW, D'Agostino RB, Levy D, Belanger AM, Sibershatz H, Kannel WB.  Prediction of coronary heart disease using risk factor categories.   Circulation   1998;97(18):1837-47.
-  Hoyert DL, Kochanek KD, Murphy SL.  Deaths: Final Data for 1997.   National Vital Statistics Reports .  Hyattsville, MD: National Center for Health Statistics; 1999.
-  Collaborative overview of randomised trials of antiplatelet therapy—I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients.   Antiplatelet Trialists' Collaboration.   BMJ   1994;308:81-106.
-  Final report on the aspirin component of the ongoing Physicians' Health Study.  Steering Committee of the Physicians' Health Study Research Group.   N Engl J Med   1989;321:129-35.
-  Peto R, Gray R, Collins R, Wheatley K, Hennekens C, Jamrozik K.  Randomised trial of prophylactic daily aspirin in British male doctors.   Br Med J (Clin Res Ed)   1988;296:313-6.
-  Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischemic heart disease in men at increased risk.  The Medical Research Council's General Practice Research Framework.  Lancet   1998;351:233-41.
-  Hansson L, Zanchetti A, Carruthers SG, et al.  Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.   Lancet   1998;280:1930-5.
-  Collaborative Group of the Primary Prevention Project (PPP).  Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomized trial in general practice.   Lancet   2001;357:89-95.
-  Roderick PJ, Wilkes HC, Meade TW.  The gastrointestinal toxicity of aspirin: an overview of randomised controlled trials.   Br J Clin Pharmacol   1993;35:219-26.
-  Dickinson JP, Printice CR.  Aspirin: benefit and risk in thromboprophylaxis.   QJM   1998;91:523-38.
-  Stalnikowicz-Darvasi R.  Gastrointestinal bleeding during low-dose aspirin administration for prevention of arterial occlusive events.   J Clin Gastroenterol   1995;21:13-6.
-  Anderson G.  Acetylsalicylic acid and the primary prevention of cardiovascular disease.  In: Canadian Task Force on the Periodic Health Examination.  Ottawa (Canada): Health Canada; 1994: 680-90.
-  Aspirin Therapy in Diabetes. American Diabetes Association.   Diabetes Care   2001;24(suppl 10):S62-S63. Available at: www.diabetes.org/clinicalrecommendations/Supplement101/S62.htm. Accessed May 25, 2001.
-  Hennekens CH, Dyken ML, Fuster V.  Aspirin as a therapeutic agent in cardiovascular disease: a statement for healthcare professionals from the American Heart Association.   Circulation   1997;96:2751-3.
-  Prevention of coronary heart disease in clinical practice.  Recommendations of the Second Joint Task Force of European and other Societies in coronary prevention.   Eur Heart J   1998;19(10):1434-1503.

### Copyright and Source Information

This document is in the public domain within the United States. For information on reprinting, contact Randie Siegel, Director, Division of Printing and Electronic Publishing, Agency for Healthcare Research and Quality, Suite 501, 2101 East Jefferson Street, Rockville, MD 20852. Requests for linking or to incorporate content in electronic resources should be sent to: info@ahrq.gov.

Source: U.S. Preventive Services Task Force. Aspirin for the Primary Prevention of Cardiovascular Events: Recommendations and Rationale. *Ann Int Med* 2001;136(2):157-60.

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## Members of the Task Force

Members of the U.S. Preventive Services Task Force are Alfred O. Berg,   M.D., M.P.H., Chair, USPSTF (Professor and Chair, Department of Family   Medicine, University of Washington, Seattle, WA); Janet D. Allan, Ph.D.,   R.N., C.S., Vice-chair, USPSTF (Dean and Professor, School of Nursing,   University of Texas Health Science Center, San Antonio, TX); Paul S.   Frame, M.D. (Tri-County Family Medicine, Cohocton, NY, and Clinical   Professor of Family Medicine, University of Rochester, Rochester, NY);   Charles J. Homer, M.D., M.P.H. (Executive Director, National Initiative   for Children's Healthcare Quality, Boston, MA); Mark S. Johnson, M.D.,   M.P.H. (Associate Professor of Clinical Family Medicine and Chairman   Department of Family Medicine, University of Medicine and Dentistry   of New Jersey-New Jersey Medical School, Newark, NJ); Jonathan D. Klein,   M.D., M.P.H. (Associate Professor of Pediatrics and of Community and   Preventive Medicine, University of Rochester School of Medicine, Rochester,   NY), Tracy A. Lieu, M.D., M.P.H. (Associate Professor, Department of   Ambulatory Care and Prevention, Harvard Pilgrim Health Care and Harvard   Medical School, Boston, MA); Cynthia D. Mulrow, M.D., M.Sc. (Professor   of Medicine, University of Texas Health Science Center, Audie L. Murphy   Memorial Veterans Hospital, San Antonio, TX); C. Tracy Orleans, Ph.D.   (Senior Scientist, The Robert Wood Johnson Foundation, Princeton, NJ);   Jeffrey F. Peipert, M.D., M.P.H (Director of Research, Women and Infants'   Hospital, Providence, RI); Nola J. Pender, Ph.D., R.N. (Professor and   Associate Dean for Research, School of Nursing, University of Michigan,   Ann Arbor, MI); Albert L. Siu, M.D., M.S.P.H (Professor of Medicine,   Chief of Division of General Internal Medicine, and Medical Director   of the Primary Care and Medical Services Care Center, Mount Sinai School   of Medicine and The Mount Sinai Medical Center, New York, NY); Steven   M. Teutsch, M.D., M.P.H. (Senior Director, Outcomes Research and Management,   Merck & Company, Inc., West Point, PA); Carolyn Westhoff, M.D.,   M.Sc. (Associate Professor of Obstetrics, Gynecology and Public Health,   Department of Obstetrics and Gynecology, Columbia University College   of Physicians and Surgeons, New York, NY); and Steven H. Woolf, M.D.,   M.P.H. (Professor of Family Medicine, Department of Family Practice, Medical College of Virginia, Fairfax, VA).

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## Contact the Task Force

Address correspondence to: Chair, U.S. Preventive Services Task Force; c/o Project Director, USPSTF; 540 Gaither Road; Rockville, MD 20850; E-mail: uspstf@ahrq.gov.

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## Available Products

This recommendation and rationale statement, plus complete information on which this statement is based, including evidence tables and references, are available on the USPSTF Web site at http://www.preventiveservices.ahrq.gov.

Individual copies of this statement are available online through the National Guideline Clearinghouse™ at: http://www.guideline.gov; or may be obtained in print from the AHRQ Publications Clearinghouse: Phone Toll-Free 1-800-358-9295; E-mail ahrqpubs@ahrq.gov.

The summary of the evidence and the recommendation statement are also available in print by subscription to the *Guide to Clinical Preventive Services, Third Edition: Periodic Updates*. Select for order form: PDF Version (230 KB), Text Version. The cost of a subscription is $60 and can be ordered through the AHRQ Publications Clearinghouse (call 1-800-358-9295 or E-mail ahrqpubs@ahrq.gov).

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*Current as of January 2002*

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**Internet Citation:**

U.S. Preventive Services Task Force. *Aspirin for the Primary Prevention of Cardiovascular Events: Recommendations and Rationale*. January 2002. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/3rduspstf/aspirin/asprr.htm

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