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Aspirin in low risk individuals

Review
Results
Comment

The question of whether prophylactic aspirin protects individuals at low risk of cardiovascular disease keeps being asked (though the exact dose at which it effective keeps being overlooked). Bandolier 86 carried a review examining the risks and benefits of aspirin use that looked at both coronary events prevented and harmful bleeds produced. The balance tipped from benefit to harm when the annual risk of a cardiovascular event was below 1%. Primary prevention is probably worthwhile at coronary risks of 1.5% a year or more, risks and benefits are balanced at an annual risk of 1%, and aspirin use is unsafe when the risk is 0.5% or less.

A new analysis of studies in low risk patients shows that aspirin use in such individuals has little or no effect on all-cause mortality.

Review

The review sought studies where aspirin was used prophylactically in low risk individuals, and where the outcome reported was all cause mortality. Low risk was defined as having no more than one of a list of risk factors, including hypertension, high cholesterol or LDL, family history, smoking, diabetes, age over 45 years in men and 55 in women, angina, and past cardiovascular events. A widespread search included MEDLINE, Cochrane, previous reviews and the Internet.

Results

No study included only low risk patients. Two randomised trials (US physicians, British doctors) and one cohort study (US nurses) met the inclusion criteria, though grouping low risk individuals with higher risk individuals known to benefit from aspirin use. The aspirin doses were 325 mg every other day, 500 mg daily, and 1-15 aspirin tablets per week, respectively.

In the two randomised trials, the only significant benefit produced was for myocardial infarction in the US physicians study, and that disappeared when combined with the British doctors study (Table 1). The nurses cohort study had significantly increased rates of heart attack, stroke and mortality associated with aspirin use.

Table 1: Description and results of individual trials examining prophylactic use of aspirin in individuals at low risk of cardiovascular disease

US physicians

UK doctors

US nurses

Description

 
Study architecture RCT RCT Cohort
Number 11,037 3,429 35,048
Duration (years) 5 6 6

Outcome and odds ratio (95%CI)

Myocardial infarction 0.6 (0.5 to 0.7) 1.0 (0.7 to 1.2) 2.3 (1.9 to 2.9)
Stroke 1.3 (0.9 to 1.6) 1.2 (0.8 to 1.7) 1.8 (1.4 to 2.4)
Cardiovascular mortality 1.0 (0.7 to 1.3) 0.9 (0.7 to 1.2) 1.7 (1.2 to 2.3)
Total mortality 1.0 (0.8 to 1.2) 0.9 (0.7 to 1.1) 1.8 (1.6 to 2.1)

Comment

While there is no doubt of the benefits of aspirin use in individuals at high risk of cardiovascular events, there is no evidence that it is beneficial in those at low risk. It can be argued that there is insufficient evidence, rather than evidence of absence of an effect. That argument is justified, but against it could be levied the counter-argument that these studies were biased in favour of aspirin efficacy by including individuals likely to benefit.

The balance of benefit, harm and dose in low risk individuals is another story that waits to be told. Almost half of the British physicians stopped because of gastrointestinal adverse effects on 500 mg a day. But what is the lowest effective dose of aspirin? Would the arguments of benefit and harm be changed by doses of 75 mg daily, or lower? If higher doses have no discernible effect in low risk individuals, would we expect lower doses to be any better?

The practical point is that, for now, there is no evidence that aspirin is of any value in benefiting cardiovascular outcomes or mortality in low risk individuals. There will probably be some harm.

References:

  1. JM Boltri et al. Aspirin prophylaxis in patients at low risk for cardiovascular disease: a systematic review of all-cause mortality. Journal of Family Practice 2002 51: 700-705.
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