To the Editor: Ridker et al. (March 31 issue)1 conclude thatprimary prophylaxis with aspirin to prevent myocardial infarctionis ineffective in young, healthy women. However, the majorityof patients in this study (84.5 percent) had a 10-year riskof less than 5 percent for an incident myocardial infarctionand therefore would not have received aspirin as primary prophylaxis,according to the American Heart Association guidelines. TheAmerican Heart Association published recommendations in 2002stating that aspirin should be used as primary prevention forcoronary events in persons with a 10-year risk of an incidentmyocardial infarction that is greater than 10 percent.2 Althoughthe results of the study by Ridker et al. are interesting, weneed a trial based on practice according to current, establishedguidelines.
Daniel J. Schwartz, M.D. Johns Hopkins Medical Institutions Baltimore, MD 21224 dschwa24{at}jhmi.edu
References
Ridker PM, Cook NR, Lee I-M, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005;352:293-304. [Free Full Text]
Pearson TA, Blair SN, Daniels SR, et al. AHA guidelines for primary prevention of cardiovascular disease and stroke: 2002 update: consensus panel guide to comprehensive risk reduction for adult patients without coronary or other atherosclerotic vascular diseases. Circulation 2002;106:388-391.
To the Editor: The press coverage of the study by Ridker etal. indicated that aspirin does not prevent heart attacks inwomen. This message is consistent with the abstract's concludingstatement, "In this large, primary-prevention trial among women,aspirin lowered the risk of stroke without affecting the riskof myocardial infarction." However, this conclusion is misleading.A more accurate statement would be that very-low-dose aspirin(100 mg every other day) is not effective in preventing myocardialinfarction in women.
In the Primary Prevention Project trial,1 100 mg of aspirinper day was effective in preventing myocardial infarction inwomen and in men. However, in the Hypertension Optimal Treatmenttrial,2 75 mg of aspirin per day was effective as preventionin men but ineffective in women. It would not be unreasonableto conclude from these three trials that the minimum dose ofaspirin needed for a cardioprotective effect is higher in womenthan in men and is greater than 75 mg per day. The study byRidker et al. did not establish that aspirin is ineffectivein preventing myocardial infarction in women.
James E. Dalen, M.D., M.P.H. University of Arizona Tucson, AZ 85718 jamesdalen{at}yahoo.com
References
de Gaetano G, Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet 2001;357:89-95. [Erratum, Lancet 2001;357:1134.] [CrossRef][Web of Science][Medline]
Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998;351:1755-1762. [CrossRef][Web of Science][Medline]
The authors reply: Dr. Schwartz correctly notes that the majorityof the participants in the Women's Health Study were at lowrisk for coronary heart disease, as measured by the Framinghamrisk score. However, 1100 participants did have a risk of coronaryheart disease that was 10 percent or greater. Among these high-riskparticipants, the findings were consistent with the overallfindings of the trial, with no significant benefit with respectto the primary end point of major cardiovascular events forwomen taking aspirin as compared with those taking placebo (61events in the aspirin group and 60 in the placebo group, P=0.74);there was a benefit for total stroke (17 events vs. 32, respectively;P=0.04) and a trend toward benefit for ischemic stroke (16 vs.29, P=0.07), and there was no benefit for myocardial infarction(32 vs. 23, P=0.15). Thus, although overall the population hada low risk of cardiovascular events, it is important to notethat there was no evidence of a modification of the effect ofaspirin according to levels of the Framingham risk score inour study.
Dr. Dalen is correct in pointing out that our trial demonstratedthat the specific dose of 100 mg of aspirin every other daywas not associated with a reduction in myocardial infarctionoverall, and he raises the important question of whether thisvery low dose was inadequate to produce a cardioprotective effectin women. Although we agree that it is certainly possible thatthe dose was inadequate, there was no direct evidence to supportthis in the Women's Health Study. We showed that levels of thromboxaneand prostacyclin were reduced with 100 mg of aspirin every otherday; we observed the expected increased risk of gastrointestinalbleeding, hemorrhagic stroke, nongastrointestinal bleeding,and peptic ulcer, and 100 mg every other day was adequate bothto lower the risk of stroke overall and to lower the risk ofmyocardial infarction as well as stroke in women 65 years ofage or older. However, the issue of the lowest effective dosein both women and men requires further research.
Paul M. Ridker, M.D. Julie E. Buring, Sc.D. Brigham and Women's Hospital Boston, MA 02215
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