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Aspirin: More Evidence That Low Dose Is All That Is Needed

  • Authors: News Author: Sue Hughes
    CME Author: Charles Vega, MD, FAAFP
  • CME Released: 3/20/2009
  • Valid for credit through: 3/20/2010, 11:59 PM EST
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Target Audience and Goal Statement

This article is intended for primary care clinicians, cardiologists, neurologists, and other specialists who care for patients at risk for cardiovascular disease.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Identify differences in cardiovascular disease events in women and men.
  2. Specify current recommendations regarding the use of aspirin to prevent cardiovascular disease.


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  • Sue Hughes

    Sue Hughes is a journalist for, part of the WebMD Professional Network. She has been with since 2000. Previously, she was science editor of Scrip World Pharmaceutical News. Graduating in pharmacy from Manchester University, UK, she started her career as a hospital pharmacist before moving as a journalist to a UK pharmacy trade publication. She can be reached at [email protected].


    Disclosure: Sue Hughes has disclosed no relevant financial relationships.


  • Brande Nicole Martin

    Brande Nicole Martin is the News CME editor for Medscape Medical News.


    Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

CME Author(s)

  • Charles P. Vega, MD, FAAFP

    Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine


    Disclosure: Charles Vega, MD, FAAFP, has disclosed an advisor/consultant relationship to Novartis, Inc.

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Aspirin: More Evidence That Low Dose Is All That Is Needed

Authors: News Author: Sue Hughes CME Author: Charles Vega, MD, FAAFPFaculty and Disclosures

CME Released: 3/20/2009

Valid for credit through: 3/20/2010, 11:59 PM EST


From Heartwire — a professional news service of WebMD

March 20, 2009 — New guidance on how aspirin should be used in both the primary and secondary prevention of coronary heart disease has come from three new reports published this week.

Two new studies deal with aspirin use in secondary prevention. These are a post hoc analysis of aspirin use in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial [1] and results of the effect of aspirin use in the Women's Health Initiative (WHI) [2]. Both of these studies found that low-dose aspirin is just as effective as a full dose for secondary prevention.

The third paper outlines new recommendations from the US Preventive Services Task Force (USPSTF) on the use of aspirin for the primary prevention of coronary heart disease [3]. These encourage men aged between 45 and 79 years and women aged between 55 and 79 years to use aspirin when the potential benefit of a reduction in myocardial infarction (MI) for men or stroke for women outweighs the potential harm of an increase in gastrointestinal hemorrhage. They say there are insufficient data to assess the balance of benefits and harms of aspirin for cardiovascular disease prevention in men and women 80 years or older and that aspirin use should not be encouraged for cardiovascular disease prevention in women younger than 55 years and in men younger than 45 years.

CHARISMA: Low-Dose Aspirin for Secondary Prevention

The CHARISMA study, published in the March 17, 2009, issue of the Annals of Internal Medicine, was a randomized trial of long-term clopidogrel vs placebo in patients with atherosclerotic disease or multiple risk factors for heart disease. Aspirin was given to all patients in the trial at a dose of 75 to 162 mg/day, but the actual dose was determined individually by each patient's doctor. The current paper is a post hoc observational analysis of the effect of aspirin by dose. Daily aspirin doses were categorized as <100 mg (n = 7180), 100 mg (n = 4961), and >100 mg (n = 3454).

Results showed no overall differences in efficacy or safety by aspirin dose. However, in the subgroup of patients randomly assigned to clopidogrel, there was a hint of reduced efficacy and increased harm with higher doses. The researchers conclude: "Lower aspirin doses (75 to 81 mg/day) may optimize efficacy and safety for patients requiring aspirin for long-term prevention, especially those taking clopidogrel."

More Reliable Data to Come From OASIS-7

In an accompanying editorial [4], Dr Shamir Mehta (McMaster University, Hamilton, ON) notes that these results extend earlier observations made in the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, with CHARISMA having a much longer follow-up and thus allowing a more realistic evaluation of the efficacy and safety of different aspirin doses for cardiovascular disease prevention.

But he points out that these results are still based on post hoc, nonrandomized comparisons and are thus subject to bias and that more reliable information on the question of aspirin dose should come from the ongoing Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS (CURRENT-OASIS-7) trial, which is the first large-scale randomized trial to directly compare aspirin doses. This trial is a 2x2 factorial study in 25,000 patients, with the first randomization to high-dose vs standard-dose clopidogrel and the second randomization to daily high-dose vs low-dose aspirin. Results are expected later this year.

WHI: Better Data on Women

The WHI study, published in the March 2009 issue of Circulation: Cardiovascular Quality and Outcomes, provides additional evidence that aspirin may reduce the risk of death in postmenopausal women who have heart disease or who have had a stroke and, in concurrence with the CHARISMA data, show that low-dose aspirin is just as effective as higher doses.

In an interview with heartwire , Dr Jacques Rossouw (chief of the WHI branch at the National Heart, Lung, and Blood Institute, Bethesda, MD), said that current recommendations for women to take aspirin for the secondary prevention of heart disease are based on clinical trials in which women have not been well represented. "Our study is wider than previous studies, in that it included women with any form of cardiovascular disease and women older than have been studied before. We found that total mortality and cardiovascular mortality were lowered in aspirin users and that the benefit does not seem to be dose-related, whereas the side effects are dose-related. So a low dose (75 mg) seems better overall than a full dose (325 mg). And if you can reduce risk with an intervention as simple as a low-dose aspirin every day, then that's quite something."

The WHI Observational Study followed 93,676 postmenopausal women between the ages of 50 and 79 for an average of eight years. Among 8928 women with stable cardiovascular disease, 4101 (46%) reported taking aspirin, of whom 30% were on 81 mg and 70% were on 325 mg. At 6.5 years of follow-up, no significant association was noted for aspirin use and all-cause mortality or cardiovascular events. However, after multivariate adjustment, regular aspirin users had a 25% lower risk of death from cardiovascular disease and a 14% lower risk of death from any cause. Aspirin use was associated with a trend toward lower risk of cardiovascular events, which did not meet statistical significance. Compared with 325 mg, use of 81 mg was not significantly different for all-cause mortality, cardiovascular events, or any individual end point.

Adjusted Hazard Ratio for Death or Cardiovascular Events in Aspirin Users vs Aspirin Nonusers

Outcome HR (95% CI) p
All-cause mortality 0.86 (0.75 - 0.99) 0.04
Cardiovascular mortality 0.75 (0.60 - 0.95) 0.01
Cardiovascular events (MI/stroke/CV death) 0.90 (0.78 - 1.04) 0.14

The researchers note that the 46% figure for aspirin use is low and that this underutilization was most pronounced in blacks and women with Medicaid insurance.

New Primary-Prevention Recommendations

The new USPSTF recommendations on the use of aspirin for primary prevention of heart disease are also published in the March 17, 2009, issue of the Annals of Internal Medicine.

They also favor low-dose aspirin, pointing out that a dose of 75 mg/day seems as effective as higher dosages, but that the risk of gastrointestinal bleeding may increase with dose.

In his editorial, Mehta notes that these guidelines were last published in 2002 and were based on trials with limited data on women, whereas the new recommendations incorporate the results of the landmark Women's Health Study (WHS), which showed no reduction in MI and death with aspirin but a significant reduction in stroke. The new recommendations thus advise use of aspirin in men to reduce MI and in women to reduce stroke.

Mehta points out that a valuable feature of the new USPSTF recommendations is the emphasis on shared decision making: discussing the benefits and risks of initiating aspirin and individualizing decision making to the specific patient or situation. But he adds that there is one group of patients who should absolutely avoid aspirin — those who are at relatively high risk for intracranial bleeding.

He concludes: "The USPSTF has provided us with an important document that is clear and user-friendly for the busy clinician. Aspirin continues to be underused, and the routine incorporation of the USPSTF's recommendations into the daily practice of clinicians will no doubt increase the use of aspirin and, in turn, prevent many thousands of cardiovascular events every year."


  1. Steinhubl SR, Bhatt DL, Brennan DM, et al. Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding. Ann Intern Med. 2009;150:379-386.
  2. Berger JS, Brown DL, Burke GL. Aspirin use, dose, and clinical outcomes in postmenopausal women with stable cardiovascular disease — the Women's Health Initiative Observational Study. Circ Cardiovasc Qual Outcomes. 2009;2:78-87.
  3. US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150:396-404.
  4. Mehta SR. Aspirin for prevention and treatment of cardiovascular disease. Ann Intern Med. 2009;150:414-416.

The complete contents of Heartwire , a professional news service of WebMD, can be found at, a Web site for cardiovascular healthcare professionals.

Clinical Context

Although cardiovascular disease is the underlying or contributing cause of death in the majority of adults in the United States, it affects women and men differently. Men have higher rates of coronary heart disease, and cardiac events occur at a younger mean age in men vs women. However, MI is more deadly in women overall. Similarly, rates of stroke are higher in men, but more women die of stroke. This is, in large part, because age is a significant risk factor for stroke, and women live longer than men.

Aspirin can be useful in the prevention of cardiovascular events among both men and women. The current recommendations from the USPSTF summarize the best practice for using aspirin as primary prevention against cardiovascular disease.

Study Highlights

  • The decision whether to initiate aspirin therapy begins with a careful assessment of an individual patient's risk. A tool derived from the Framingham Heart Study uses sex, age, smoking status, diabetes, blood pressure, and cholesterol levels to determine the 10-year risk for coronary heart disease.
  • Men derive benefit from aspirin in their risk for MI, whereas aspirin protects women against stroke. In the WHS, the relative risk for stroke in patients receiving aspirin vs placebo was 0.83. Aspirin reduced the risk for ischemic stroke by 24% but did not affect the risk for hemorrhagic stroke.
  • In a meta-analysis, the use of aspirin was associated with an odds ratio of 0.68 for MI among men, but aspirin was not protective against stroke.
  • There are limited data suggesting that aspirin can reduce the risk for overall mortality when used as primary cardiovascular prevention.
  • The benefits of aspirin must be balanced against the risk for gastrointestinal tract bleeding. In the WHS, aspirin increased the relative risk for serious gastrointestinal tract bleeding events vs placebo by 1.40. In the larger meta-analysis, the odds ratio of major bleeding events associated with aspirin therapy was approximately 1.7 for both sexes.
  • In low-risk adults younger than 60 years, the rate of serious gastrointestinal tract bleeding is 0.8 per 1000 person-years in men receiving aspirin and 0.4 per 1000 person-years in women receiving aspirin. However, older age, a history of upper gastrointestinal tract pain, and a history of gastrointestinal tract ulcer all significantly increase the risk of gastrointestinal tract bleeding with aspirin.
  • The final recommendations suggest that aspirin should be considered to reduce the risk for MI in men between the ages of 45 and 79 years, and aspirin should be considered for reducing the risk for stroke in women between the ages of 55 and 79 years.
  • Aspirin should be started only in patients for whom the potential benefit outweighs the potential risk. For men at the following age levels and the following 10-year risk levels for coronary heart disease, the cardiovascular benefit of aspirin closely resembles the risk for serious bleeding events:
    • Ages 45 to 59 years: 10-year coronary heart disease risk, 4%
    • Ages 60 to 69 years: 10-year coronary heart disease risk, 9%
    • Ages 70 to 79 years: 10-year coronary heart disease risk, 12%
    Similarly, the following data present the 10-year stroke risk in women at which benefits of aspirin are similar to the risk for serious bleeding events:
    • Ages 55 to 59 years: 10-year stroke risk, 3%
    • Ages 60 to 69 years: 10-year stroke risk, 8%
    • Ages 70 to 79 years: 10-year stroke risk, 11%
  • There is insufficient evidence to recommend for or against the use of aspirin to prevent cardiovascular disease in adults 80 years or older.
  • The USPSTF recommends against the use of aspirin to prevent cardiovascular disease in women younger than 55 years and men younger than 45 years.

Pearls for Practice

  • Both MI and stroke are more common in men vs women, but women are more likely to have a fatal MI. Also, more women vs men die of stroke.
  • The current recommendations from the USPSTF suggest that aspirin may be used to prevent MI in men and stroke in women, provided this benefit outweighs the risk for serious bleeding events. However, aspirin treatment is not recommended as primary prevention in women younger than 55 years and in men younger than 45 years.


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