Low-Dose Aspirin in the Primary Prevention of Cancer
abstract & commentary
By Barbara A. Phillips, MD, MSPH
Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington, KY Dr. Phillips serves on the speaker’s bureau of Cephalon, Boehringer Ingelheim, Merck, ResMed, and GlaxoSmithKline and is a consultant for Boehringer Ingelheim, Wyeth-Ayerst, and ResMed.
Synopsis: There was no overall effect of 100 mg aspirin every other day on total cancer among nearly 40,000 women randomized to aspirin or placebo and followed for an average of 10 years.
Source: Cook NR, et al. Low-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trial. JAMA. 2005;294:47-55.
This study comes from the women’s health study (whs), a trial designed to test the effect of low-dose aspirin, beta carotene and vitamin E on rates of cancer and cardiovascular disease in women. The trial is described in detail elsewhere.1,2 In brief, this report includes 39,876 women who were extremely well characterized and who were followed carefully for about a decade. Their mean age at entry was 54.6 years. Participants were randomized to receive either aspirin 100 mg every other day, or placebo, and were followed after the first 6 months and then annually by questionnaire. The study medications were provided on calendar packs, and compliance for both groups was about 73%. Age, smoking history, menopausal status, body mass index, alcohol consumption, use of hormone replacement therapy, family histories of cancer, and level of physical activity were quantified and controlled in analyses. All of the women were followed for the occurrence of any cancer (including colon polyps) or cardiovascular event. The placebo and active treatment groups were well-matched.
At an average of 10-years follow-up, there were no statistically significant differences in the rates of development of breast, colorectal, lung, or several other site-specific cancers (nonmelanoma skin cancer was excluded from analysis). There were no differences in specific cancer types in level of invasiveness/stage, cell type, or receptor positivity. Overall cancer mortality was no different between groups, and there was no difference in cancer mortality for any of the cancer types except for a reduced mortality rate for lung cancer in the aspirin group (RR, 0.70; CI, 0.50-0.99; P = 0.04). There was a difference in the aspirin effect by smoking status—but in an unexpected direction. Never smokers had an increased risk of total cancers among those assigned to aspirin, with no effect among current smokers.
Commentary
Remember the Woody Allen movie, Sleeper, when he plays a character who is transported far into the future? He befuddles all the people he meets with his strange notions. Two of his futuristic pals are discussing his aberrant beliefs about nutrition, and one says to the other, "Imagine. He thinks hot fudge sundaes are bad for you!" The other muses sadly, "Hmmm, exactly the opposite of what we now know to be true." This is somewhat similar to the findings reported recently in JAMA3 in which the author reports, "Of 49 highly cited original clinical research studies, 45 claimed that the intervention was effective. Of these, 7 (16%) were contradicted by subsequent studies, 7 others (16%) had found effects that were stronger than those of subsequent studies, 20 (44%) were replicated, and 11 (24%) remained largely unchallenged." In other words, contradiction and initially stronger effects are not unusual in highly cited research of clinical interventions and their outcomes.
The current report and its companion4 about vitamin E from the WHS continue this tendency of randomized controlled trials to reverse or soften findings of earlier, clinical studies. These larger, more carefully done studies show that neither vitamin E nor aspirin is associated with a reduced risk of any of the cancers investigated, although aspirin may be associated with a reduced risk of lung cancer mortality. The companion study on vitamin E did find a reduction in cardiovascular mortality (RR, 0.75; CI, 0.59-0.98; P = 0.03) in those women randomized to 600 IU of natural source vitamin E.4
Findings from these studies (and almost any report from the WHS) are making their way into the lay press, because the media knows what we should know—women are intensely interested in health promotion and prevention of disease. Women are more likely than men to take vitamins and supplements, and women who do take vitamins and supplements are more likely to engage in healthy lifestyles, which may include seeking medical care and advice.5 For the primary care practitioner, keeping abreast of findings about vitamins, supplements and health promoting behaviors is important because it is important and relevant to our patients.
So what should we tell our patients about aspirin and vitamin E? With regard to aspirin, it is possible that the dose (100 mg) was too small and the duration of treatment not long enough to see an effect; but for now, taking either aspirin or vitamin E are poor strategies to prevent cancer. The story on cardiovascular disease is more encouraging; the WHS demonstrates a reduced risk of cardiovascular death with 600 mg vitamin E every other day (though doses of 400 IU/day may be associated with increased mortality).6 The study also demonstrated that aspirin significantly reduced the risk of major cardiovascular events, ischemic stroke, and myocardial infarction among women 65 years of age or older.1 Importantly, gastrointestinal bleeding requiring transfusion was more frequent in the group that received aspirin. Cook and colleagues concluded, "At present, in the primary prevention of CVD and cancer, therapeutic lifestyle changes including a healthy diet and control of major risk factors remain important clinical and public health strategies." This is definitely a "half-empty" (conservative) conclusion. The WHS did demonstrate reduced adverse cardiovascular events in some subgroups with both aspirin (100 mg every other day) and vitamin E (600 IU every other day). Heart disease is the leading killer of both men and women, and even modest reduction in risk is worth recommending.
References
1. 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;352:1293-1304.
2. Rexrode KM, et al. Baseline characteristics of participants in the Women’s Health Study. J Womens Health Gend Based Med. 2000;9:19-27.
3. Ioannidis JP. Contradicted and Initially Stronger Effects in Highly Cited Clinical Research. JAMA. 2005;294:218-228.
4. Lee IM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA. 2005;294:56-65.
5. McNaughton SA, et al. Supplement use is associated with health status and health-related behaviors in the 1946 british birth cohort. J Nutr. 2005;135:1782-1789.
6. Eidelman RS, et al. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med. 2004;164:1552-1556.
By Barbara A. Phillips, MD, MSPH Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington, KY Dr. Phillips serves on the speakers bureau of Cephalon, Boehringer Ingelheim, Merck, ResMed, and GlaxoSmithKline and is a consultant for Boehringer Ingelheim, Wyeth-Ayerst, and ResMed. Synopsis: There was no overall effect of 100 mg aspirin every other day on total cancer among nearly 40,000 women randomized to aspirin or placebo and followed for an average of 10 years.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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