December 16th, 2009
To Recommend Aspirin or Not to Recommend Aspirin, That Is the Question
Joseph S. Ross, MD, MHS
The debate over the use of aspirin in primary prevention of cardiovascular events among adults with no known cardiovascular disease continues to grow. In March, the United States Preventive Services Task Force assigned Class A recommendations to encourage:
Men 45-79 to use aspirin when potential MI benefit outweighs potential GI harm
Women 55-79 to use aspirin when potential stroke benefit outweighs potential GI harm
No controversy yet. As before, physicians are being told that aspirin is a “must use” drug among patients at moderate risk of either MI or stroke.
However, since the USPSTF recommendation, several studies have presented data that contradict this Class A recommendation, including a meta-analysis from the Oxford Antithrombotic Treatment Trialists (ATT) published in the Lancet.
This analysis is particularly interesting because previous meta-analyses only made use of summary-level data. However, through a collaborative agreement established among principal investigators of the large trials of aspirin for primary prevention, subject-level data (n=95,000) was made available for this paper. This agreement allowed for reliable comparisons of both the benefits and risks of aspirin in important groups, such as older adults, adults with diabetes, and others at increased risk of coronary heart disease. I recently collaborated on a research paper published in Archives of Internal Medicine that advocated for the availability of subject-level data for meta-analysis for purposes such as this.
The Oxford ATT found that aspirin was not associated with a reduced rate of vascular death but was associated with a 12% relative risk reduction per year in the primary prevention of serious vascular events. However, the absolute event rates per year were low (0·51% for aspirin recipients vs. 0·57% for controls), and the absolute risk reduction was reported as 0.07% (NNT>1000 for 1 year of treatment). This reduction was due mainly to fewer non-fatal myocardial infarctions. Complicating matters, aspirin was also associated with more major gastrointestinal and extra-cranial bleeds, with an absolute harm increase of 0.03% per year.
Within the pre-specified sub-group analyses, there was no significant heterogeneity in their findings: the risk reduction in primary prevention of serious vascular events was similar regardless of patient age, sex, BMI, past medical history of diabetes, hypertension, hyperlipidemia, or predicted 5-year CHD risk.
Perhaps we will have a better understanding when the results of ASPREE, ACCEPT-D, and ASCEND are available. We can only hope that the principal investigators enter into the same collaborative agreement and share subject-level data for meta-analysis.
Nevertheless, given this more precise examination of existing data, I cannot see how aspirin can remain a “must-use” drug for primary prevention of cardiovascular events among patients at moderate risk of either MI or stroke since there is minimal net effect on serious vascular events and no effect on mortality.
Do you agree? And what will you suggest to your primary care colleagues, like me, who are making decisions as to whether to recommend aspirin among large groups of patients with no known cardiovascular disease?
5 Responses to “To Recommend Aspirin or Not to Recommend Aspirin, That Is the Question”
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What to do with aspirin?
Taking a 10 year perspective, consider that
1. Treating 1000 low risk people (1% risk at 10 years of CHD) you could prevent 1 MI (from 10 in 1000 to 9 in 1000) but cause 3 more severe bleeds (mostly gastrointestinal).
2. Treating 1000 mid risk people (10% risk at 10 years of CHD- fairly typical of outpatient DM2 for instance) you could prevent 12 MIs (from 100 in 1000 to 88 in 1000) but cause 3 more severe bleeds (mostly gastrointestinal). We just published a paper in Diabetes Care showing that the evidence in this population, contrary to narrow interpretation inclusive only of recent papers, is consistent with the risk reduction seen in the overall primary prevention population.
3. Treating higher risk patients and secondary prevention patients is associated with even larger reductions in absolute terms in the risk of CHD events while the harm risk appears to remain fairly constant at low doses of aspirin (in secondary prevention some patients would add on clopidrogel and then balance may get challenging again, except the benefit may also get a bit better).
So, when it comes to aspirin, just as when it comes to statins, the idea is to evaluate the CHD risk for your patient and then see what risk reductions you can expect and balance this with the harm. Since this is NOT a technical decision, you may want to involve patients in choice. Our group is developing a decision aid that people can use in practice to do just that. So I agree – for many low risk patients it is no longer a “must-use”.
More questions than answers….
Great post and comment. It seems that the right course of action is becoming less and less clear with each new study that gets published. Hopefully the future aspirin studies mentioned above will provide some clarity. However, a few key questions come to mind: 1) While awaiting a decision aid (which would be really helpful), how do you think we should try to make these decisions for patients? Would you say generally no aspirin for all low to moderate risk patients and then reserve for only high risk? Any exceptions? 2) If so, how do you define high risk? Based on Framingham risk score or some other measure? 3) And finally, what do you with the large number of patients who are already on a “baby aspirin” daily? Are the data strong enough to discontinue daily ASA dose in the low-risk subgroup?
Victor and Maulik, thanks for your comments. I am very much looking forward to Victor’s decision aid, because it remains a challenge to explain asprin’s risks and benefits in a way that I can be most certain that my patients understand them. For now, I have been attempting to readdress the decision to use aspirin among my low and moderate risk patients, essentially older adults, adults with diabetes, high blood pressure or hyperlipidemia, and adults who use tobacco. My inclination is to discontinue the drug, but I lay out the evidence for patients and allow them to make an informed decision (or as informed as possible in the 15 minutes I have with them!). At the same time, I try to take a moment to reinforce the decision to use aspirin among my highest risk patients, still taking the time to readdress the risks and benefits but clarifying that, to the best of our knowledge, aspirin remains an important drug in their armamentarium.
tools for patients
Seems to me that patients need heuristics — most will not want to get into the math — and so how do we construct these rules of thumb for them? and us?
Should it be that if you have no history of heart disease or strong family history — and your modifiable risk factors are being treated — then you have little to gain.
Isn’t it that simple?
Media interpretation
I agree that this paper challenges if not debunks the theory that many have held, namely that aspirin should be given even in low risk patients. The problems I have encountered since the publication of this paper is that intermediate-high risk patients who we have been treating with ASA are now asking if they should be taking it. This is largely due to the warranted media-buzz and publicity that surrounded this paper. However as can often happen, this has resulted in the findings being misrepresented and misinterpreted.