Tipos de factores de riesgo ergonómico

M IC H A E L E . H O C H M A N

[The Physicians’ Health Study] demonstrates a conclusive reduction in the risk of myocardial infarction [in men], but the evidence concern-ing stroke and total cardiovascular deaths remains inconclusive  .  .  . as expected, [aspirin led to] increased risks of upper gastrointestinal ulcers and bleeding problems.

—The Physicians’ Health Study Research Group¹ [In the Women’s Health Study] aspirin lowered the risk of stroke with-out affecting the risk of myocardial infarction or death from cardio-vascular causes . . . as expected, the frequency of side effects related to bleeding and ulcers was increased.

—Ridker et al.²

Research Question: Is aspirin effective for the prevention of cardiovascular disease in apparently healthy adults?^1,2

Funding: The Physicians’ Health Study was sponsored by the National Institutes of Health, and the Women’s Health Study was sponsored by the National Heart, Lung, and Blood Institute and the National Cancer Institute.

Year Study Began: 1982 (Physicians’ Health Study) and 1992 (Women’s Health Study)

Year Study Published: 1989 (Physicians’ Health Study) and 2005 (Women’s Health Study)

Study Location: The Physicians’ Health Study was open to apparently healthy male physicians throughout the United States who were mailed invitations to participate. The Women’s Health Study was open to apparently healthy female health professionals throughout the United States who were mailed invitations to participate.

Who Was Studied: The Physicians’ Health Study included apparently healthy male physicians 40–84, while the Women’s Health Study included apparently healthy female health professionals ≥45.

Who Was Excluded: Patients were excluded from both trials if they had exist-ing cardiovascular disease, cancer, other chronic medical problems, or if they were currently taking aspirin or nonsteroidal anti-inflammatory agents. Both trials included a run-in period to identify patients unlikely to be compliant with the study protocol, and these patients were excluded before randomization.

How Many Patients: The Physicians’ Health Study included 22,071 men, while the Women’s Health Study included 39,876 women.

Study Overview: See Figure 3.1 for a summary of the trials’ design.

Study Intervention: In the Physicians’ Health Study, patients in the aspirin group received aspirin 325 mg on alternate days while in the Women’s Health Study patients in the aspirin group received aspirin 100 mg on alternate days. In both trials, patients in the control group received a placebo pill on alternate days.

Apparently Healthy Adults Randomized

Aspirin Placebo

Figure 3.1 Summary of the Study Design.

Aspirin for the Primary Prevention of Cardiovascular Disease 17

Follow-Up: Approximately 5  years for the Physicians’ Health Study and approximately 10 years for the Women’s Health Study.

Endpoints: Myocardial infarction, stroke, cardiovascular mortality, and hem-orrhagic side effects.

RESULTS

• In both trials, aspirin led to a small reduction in cardiovascular events but an increase in bleeding events (see Tables 3.1 and 3.2).

• In both trials, aspirin was most beneficial among older patients (men

≥50 and women ≥65).

Criticisms and Limitations: In the Physicians’ Health Study, aspirin 325 mg was given on alternate days while in the Women’s Health Study aspirin 100 mg was given on alternate days. In clinical practice, however, most patients receive aspirin 81 mg daily (data concerning the optimal ASA dose are sparse).

Both of these trials are limited in generalizability. Both included patients of high socioeconomic status. In addition, patients found to be noncompliant during a run-in period were excluded. Patients in the general population are

Table 3.1. Summary of the Physicians’ Health Study’s Key Findings Outcome Aspirin Group Placebo Group P Value

Myocardial Infarction 1.3% 2.2% <0.00001

Stroke 1.1% 0.9% 0.15

Cardiovascular Mortality 0.7% 0.8% 0.87

Gastrointestinal Ulcers 1.5% 1.3% 0.08

Bleeding Requiring

Transfusion 0.4% 0.3% 0.02

Table 3.2. Summary of the Women’s Health Study’s Key Findings Outcome Aspirin Group Placebo Group P Value

Cardiovascular events^a 2.4% 2.6% 0.13

Stroke 1.1% 1.3% 0.04

Myocardial Infarction 1.0% 1.0% 0.83

Cardiovascular Mortality 0.6% 0.6% 0.68

Gastrointestinal Bleeding 4.6% 3.8% <0.001

a Includes myocardial infarction, stroke, and death from cardiovascular causes.

likely to be less compliant with therapy, and therefore the benefits of aspirin observed in real-world settings may be lower.

Other Relevant Studies and Information:

• Other trials of aspirin for cardiovascular disease prevention have also suggested that aspirin reduces the risk of cardiovascular events while increasing bleeding risk.³

• Some data have suggested that aspirin decreases the incidence of colorectal cancer, but the benefits appear modest and more data are needed to confirm this conclusion.⁴

• Whether aspirin has a differential effect on men and women is unclear: one meta-analysis suggested that in men aspirin may preferentially prevent myocardial infarctions while in women aspirin may preferentially prevent strokes.⁵ Other experts believe this conclusion is premature, however.⁶

• Aspirin is also effective in preventing cardiovascular events in high-risk patients with vascular disease,⁷ and the absolute benefits are greater among these patients.

The American Heart Association recommends daily aspirin for apparently healthy men and women whose 10-year risk of a first event exceeds 10%, while the US Preventive Services Task Force recommends low-dose (e.g., 75 mg) daily aspirin for primary cardiovascular prevention in the following circumstances:

• In women 55–79 when the reduction in ischemic stroke risk is greater than the increase in gastrointestinal hemorrhage risk (e.g., a woman with a high stroke risk but low bleeding risk would be a good candidate while a woman with a high bleeding risk but low stroke risk would not be).

• In men 45–79 when the reduction in the risk of myocardial infarction is greater than the increase in gastrointestinal hemorrhage risk (e.g., a man with a high risk of myocardial infarction but low bleeding risk would be a good candidate while a man with a high bleeding risk but low risk of myocardial infarction would not be).

Summary and Implications: In apparently healthy men and women, aspirin leads to a small reduction in the risk of cardiovascular disease while increas-ing bleedincreas-ing risk. In men, aspirin may preferentially prevent myocardial infarc-tions, while in women aspirin may preferentially prevent strokes, though this

Aspirin for the Primary Prevention of Cardiovascular Disease 19

conclusion is uncertain. Aspirin can be considered for primary cardiovascular prevention in both men and women with cardiovascular risk factors when the risk of gastrointestinal hemorrhage is low.

References

1. The Physicians’ Health Study Research Group. Final report on the aspirin compo-nent of the ongoing Physicians’ Health Study. N Engl J Med. 1989;321(3):129–135.

2. Ridker PM et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352(13):1293–1304.

3. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and sec-ondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849.

4. Dubé C et al. The use of aspirin for primary prevention of colorectal cancer: a sys-tematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med. 2007;146(5):365.

CLINICAL CASE: ASPIRIN FOR THE PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE Case History:

A 60-year-old woman with a history of hypertension, hyperlipidemia, liver cirrhosis, esophageal varices, and recurrent gastrointestinal bleeding asks whether she should receive aspirin to reduce her risk of cardiovascular dis-ease. Based on the results of the Women’s Health Study, what would you recommend?

Suggested Answer:

The Women’s Health Study demonstrated that, in female health profession-als ≥45, daily aspirin leads to a small but detectable reduction in the risk of cardiovascular disease while increasing bleeding risk. The US Preventive Services Task Force recommends low-dose daily aspirin in women 55–79 when the reduction in cardiovascular risk is judged to be greater than the increase in risk of gastrointestinal hemorrhage.

The patient in this vignette has risk factors for cardiovascular disease and therefore might be a candidate for aspirin. However, she has numerous risk factors for gastrointestinal bleeding, making aspirin therapy risky. Overall, the risks of aspirin likely outweigh the benefits in this patient.

5. Berger JS et  al. Aspirin for the primary prevention of cardiovascular events in women and men:  a sex-specific meta-analysis of randomized controlled trials.

JAMA. 2006;295(3):306.

6. Hennekens CH et al. Sex-related differences in response to aspirin in cardiovascu-lar disease: an untested hypothesis. Nat Clin Pract Cardiovasc Med. 2006;3:4–5.

7. Berger JS et al. Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis. Am J Med. 2008;121(1):43.

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