February 19th, 2010
Who Does and Who Doesn’t Get Aspirin? Can We Do Better?
Christopher Paul Cannon, MD
Aspirin is the best known and most widely used preventive therapy. A century of clinical experience and randomized trials in over 250,000 patients have proved its benefit in preventing cardiovascular events, and it costs pennies a day. So how can it be that not everyone who needs it gets it?
In a new report, we used prospective, longitudinal data from REduction of Atherothrombosis for Continued Health, a unique registry of outpatients with established atherothrombosis or multiple risk factors, to look at current, “real world” practices of cardiovascular protection. Of more than 25,000 U.S. participants, we found that approximately one quarter of those with vascular disease are not treated with aspirin for secondary prevention, and 15% are not treated with any antithrombotic agent (i.e., aspirin, warfarin, or other antiplatelet agents). Of patients who had risk factors only (i.e, no history of MI, stroke, or peripheral arterial disease), one third were not taking any antithrombotic agent.
So, I see two issues here:
we need to try to make sure that all patients with vascular disease get aspirin (or another antithrombotic agent), and
we need o determine which patients who are at risk for — but have not yet developed — vascular disease should also be receiving such treatment.
1. Secondary prevention. We didn’t ask investigators why they were not treating individual patients with aspirin. Asking that question would be the next step in a quality-improvement initiative to try and extend aspirin treatment to 100% of eligible patients (understanding that some have contraindications). One option for clinicians who use electronic medical records would be to get an automatic reminder that the patient should be on aspirin or another antithrombotic agent whenever we enter a diagnosis of MI, stroke, or PAD or performance of PCI or CABG.
2. Primary prevention. Here, the data are more mixed. A recent analysis by the Antithrombotic Trialists Collaboration found that although patients with only risk factors benefit from treatment, the benefit is very small in low-risk patients: just an 0.25% absolute reduction in cardiovascular death, MI, or stroke per year of treatment. The ATT investigators also reported an increase in bleeding of about half the amount of absolute reduction in occlusive events. Thus, the key question remains: how many patients who do not have cardiovascular disease should be treated with aspirin?
I agree with Drs. Tapp, Shansila, and Lip, the editorialists who commented on the REACH report, who call for a reconsideration of international guidelines regarding aspirin in primary prevention.
What do you do in your practice? Do you prescribe aspirin for 100% of your patients with vascular disease? How do you handle primary prevention? What does your institution need to do to improve antithrombotic use?
10 Responses to “Who Does and Who Doesn’t Get Aspirin? Can We Do Better?”
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Key Question
Nice blog and important issue — how do we manage conversations with patients about the use of aspirin for primary prevention. The data are challenging for doctors to understand — let alone patients. The ATT analysis also challenges what was published only a couple a months before the ATT publication by the US Preventive Task Force. The challenge here is to explain the issues adequately and make sure what patients are doing is best fitting their preferences — and that they really understand the balance of risks and benefits.
Issue 2 – “we need to determine which patients who are at risk for — but have not yet developed — vascular disease should also be receiving such treatment”
I think the only way to do this is through some form of subclinical vascular disease imaging technology. They all have upsides and downsides but it is pretty clear to me that they add to the Framingham Risk Score (which misses about 22% of events based on its statistical characteristics – ie ROC curve). Seeing vascular disease in a patient who presents with a certain set of risk factors – that to me is a wonderful advance in our modern therapeutic armamentarium. Otherwise one runs the risk of treating vascular disease “blindly”.
imaging to guide decision making
I like Dan’s idea of imaging a lot, as potentially a powerful tool to help us further risk stratify. The issue I struggle with is where to define the cut-off. Seems easier for presence versus absence of something like CAC, but for something like IMT, where there seems to be more of a continuum, where and how should we draw the line? Maybe the lowest hanging fruit for studies to test this would be clear evidence of asymptomatic focal plaque (soft or hard). Then there’s the issue of who to screen and at what cost. Maybe simple risk scores could help us better decide who to image…
Blind Treatment
Dan and Susan, to me, there is little controversy over using aspirin for secondary prevention — the issue is adherence and ensuring that patients are offered aspirin and then use it regularly — so imaging plays no role here. However, controversy remains over using aspirin for primary prevention and I simply cannot believe that subclinical vascular disease imaging represents a feasible and practical (and affordable) approach to stratifying vascular disease risk in order to recommend (or not) aspirin for primary prevention of low risk patients. In your opinions, how would you best incorporate imaging to make better clinical decisions? What range of 10 year risk scores would merit imaging, as opposed to feeling comfortable simply recommending aspirin for primary prevention and focusing on adherence? For patients whose 10 year risk sits between 10-20%? And is there a level of risk above which you would simply recommend aspirin? Above 20%? 30%?
vascular disease imaging
Most patients in whom I would consider ASA in primary prevention are actually not at all primary prevention once we have imaged their carotids – they have asymptomatic, subclinical, occult carotid vascular disease (usually with high total plaque area). Actually the discussion is moot as I would recommend statins first before aspirin in such patients, given the recent evidence from JPAD, POPADAD, and AAA (published today in JAMA). I won’t ever go back to seeing patients without having full images of their carotids first – otherwise, I would be treating them blindly. (PS to Susan – the threshold I would use is a total plaque area of around 0.4 or 0.5 cm2 to recommend drug preventive therapy).
Imaged vascular disease
The imaging idea seems to be something that is reasonable, although, One other study out today – the AAA study found no benefit of aspirin in patienst with a low ABI. this was an asymptomatic PAD group, and suggests that more is needed to identify patients at risk. This makes me think of the CHARISMA analysis by Deepak Bhatt – of who benefits from clopidogrel + ASA vs. ASA alone. Those with prior MI did, but those with prior CAD, but no MI did not. Thus, patients seem to have needed to have had a clinical event to benefit. For ASA and all antiplatelet therapies, we also might need some evidence of instability clinically to see who benefits. Intersting times..
Primary Use is For Secondary Prevention
Chris hit the nail on the head. Aspirin therapy for primary prevention — even in “high risk population”, such as those with diabetes mellitus or PVD) — has been disappointing. Conversely, it has been effective for secondary prevention (s/p TIA/CVA, MI, ACS).
Calcium score >400
When the coronary calcium score is > 400, the risk for a heart attack is greater than the risk of a second heart attack in someone who has already survived a first. It seems logical to me that a CAC score >400 should be a solid indication for aspirin (in addition to agressive risk factor management) in the primary prevention arena.
Competing interests pertaining specifically to this post, comment, or both:
I love preventing heart attacks. I despise strokes. I have an ownership interest in a facility that can perform coronary calcium imaging and carotid ultrasound imaging.
ASA for high calcium score
I agree this would be a reasonable approach – although we don’t have a trial per se of this as a screening tool/indication. It would raise the predicted risk of MI or CV death, so if we look at the ATT Collaborative paper (reverences and linked in the first post – it would be a reasonable group where the event prevention would be much greater in absolute terms than the bleeding.
Statin before ASA in primary prevention
I am moving more and more to the thinking of the ATT analysis that primary prevention patients, unless they are really occult secondary prevention patients load with subclinical plaque, do not benefit from ASA after statin is on board. We would of course use both, and also antihypertensive and glucose-lowering therapy, in primary prevention patients who are revealed to have vascular disease on non-invasive imaging such as carotid total plaque area assessment or CAC.