Does Aspirin Prevent Cardiovascular Disease and Cancer? Ignore the Guidelines

An Expert Interview With Charles H. Hennekens, MD, DrPH

Linda Brookes, MSc; Charles H. Hennekens, MD, DrPH


October 29, 2014

In This Article

Gender Differences in Aspirin's Effects?

Medscape: Are there gender differences in the effects of aspirin in CVD prevention, as suggested after the WHS results were published?[41]

Dr Hennekens: Absolutely not. I was founding principal investigator of the PHS, which was the first to show a statistically significant and clinically important benefit of aspirin in men with first MI,[1] as well as the WHS, which was the first to show a statistically significant and clinically important benefit of aspirin in women with first stroke.[27] Some erroneously concluded gender differences from this finding. Several lines of reasoning do not support this hypothesis. For example, in the secondary prevention trials, which have far larger numbers of endpoints, subsequent risks for MI or stroke are the same in men and women. In primary prevention, MI becomes the leading killer in men by age 45 years, but it doesn't become the leading killer in women until age 65 years. But by the end of life, 1 in 3 men and 1 in 3 women die from coronary heart disease.

An occlusive event in a middle-aged man is most likely to be an MI, whereas in a woman, until age 65, it is more likely to be a stroke. In the WHS, 90% of the women were under age 65. In a subgroup analysis useful to formulate the hypothesis, women aged 65 years or older accounted for over 30% of the endpoints, and there were statistically significant benefits of aspirin during a first stroke as well as during a first MI.

So, in my opinion, the benefits of aspirin are the same in men and women.

Premenopausal women who are nonsmokers are extremely unlikely to experience an MI, but cigarettes increase their risk 13-fold.[42] From the time of conception, men have higher absolute risks for death compared with women until about age 105!

Medscape: How do factors such as diabetes or obesity weigh against gender in terms of risk?

Dr Hennekens: It's interesting that you mention that, because the clinical adage is that long-standing diabetes in a woman basically neutralizes the gender benefit on MI because diabetes doubles the risk in men but increases the risk three- to sixfold in women. With respect to the use of aspirin in diabetics, the ASCEND trial[10] has enrolled over 10,000 people with diabetes.

In regard to obesity, this risk factor is emerging in the United States and worldwide as perhaps the leading avoidable cause of premature death in men and women.

Medscape: What about the role of aspirin in prevention of cancer?

There is direct randomized evidence that aspirin prevents colon polyps and recurrent colon cancer. With respect to other cancers, there has been a reliance on observational studies, which cannot be used to test hypotheses of small benefits, as well as subgroups of particular trials, which are also useful to formulate but not test hypotheses. In that regard, in ISIS-2 (Second International Study of Infarct Survival), aspirin conferred a 23% reduction in mortality when given during acute MI. Subgroups that appeared to benefit equally included men and women, the elderly and middle aged, diabetics and nondiabetics, and hypertensives and non-hypertensives. There was one subgroup that aspirin didn't benefit: patients born under the star sign of Gemini or Libra.[37] Thus, ISIS-2 formulated a hypothesis that we tested in the Physicians' Health Study which showed that the only birth sign that did not benefit was Scorpio.

In regard to aspirin in cancer prevention, we shouldn't be overemphasizing particular subgroups or particular categories rather than looking at all the evidence, in particular those trials with longer durations of treatment and follow-up.


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