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Thursday, September 12, 2019

Is it time to stop primary prophylaxis with low dose aspirin

Well, it might be if one construes broadly-perhaps too broadly- the results of a  systematic review published in the Lancet. See here for summary- registration needed for full text) Also see here for a good discussion and some details of the study.

The authors meta-analyzed some six studies with mega numbers of patient years on the table and basically concluded that in secondary prophylaxis the beneficial reduction in heart attack trumps the risk of bleeding while in those individuals without established diagnosis of coronary disease the bleeding risk appeared greater than the heart attack risk reduction.This study is said to be more informative than an earlier meta-analysis of the same six studies because of access to some individual patient data.

The NCEP formula for heart attack risk estimate is based on data from The Framingham study.The current version of that formula cranks out a ten year risk of 24% for a 70 year old,non-smoking male, with a BP of 140 on blood pressure meds,a total cholesterol of 230 and an HDL of 40. Widely quoted guidelines would all agree that one should recommend low dose aspirin for such a patient. Does the new meta-analysis have sufficiently fine grained subgroup data to alter that recommendation?

An important insight to the data is the following.(quote is from the second link mentioned above)My bolding

This proportional reduction in serious vascular events did not depend significantly on age, sex, smoking history, blood pressure, total cholesterol, body-mass index, history of diabetes, or predicted risk of coronary heart disease. The authors point out that there was not even a significant trend in the proportional effects of aspirin in people at very low, low, moderate, and high estimated risk of coronary heart disease. "If the proportional risk reductions in these different subgroups really are similar, then the absolute risk reductions will depend chiefly on an individual's absolute risk without treatment," the authors comment.

I don't think this is anything new or surprising but the following could be:
They also say that their analysis suggests that the same factors that determine risk of heart disease also determine the risk of bleeding with aspirin, so that, even for people at moderately increased risk of coronary heart disease, the major absolute benefits and hazards of adding aspirin to a statin-based primary-prevention regimen could still be approximately evenly balanced.
So apparently not only heart attack risk increases with increased risk factors but so does the risk of bleeding.

There is an argument that since we now have statins as an arrow in the preventive medicine quiver and they seem so effective and also seem to do; God- only- knows how many other beneficial things maybe aspirin with its precarious and ambiguous balancing of thrombosis prevention and bleeding may not be for everybody in regards to primary prophylaxis.

The meta-analysis was published in May 2009 so the most recent guidelines from the U.S. Preventive Services Task Force could not have taken its findings into consideration. This version of their recommendations give different advice for men and women. For men they say:

Men aged 45 to 79 with heart risk factors should take aspirin if the preventive benefits outweigh the risk of bleeding. The trick is , of course, to somehow discern if the benefits outweigh the risk.

Even the practice of using low dose aspirin for primary prophylaxis in diabetes has come under attack. This article in the BMJ makes the argument that evidence supporting aspirin use is weak even though their analysis did show a 43% decrease in myocardial infarction men, but not women.

Doctor, were you wrong then or are you wrong now?



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