Making an Informed Clinical Judgment
Medscape: Has the message or the mechanism been misinterpreted over all these years?
Dr Hennekens: Aspirin is as old as medicine itself, and in the 20th century it was the most widely used drug in the entire world. But it really wasn't until Sir John Vane showed in 1971 how aspirin inhibits prostaglandins and how even small amounts of aspirin irreversibly acetylate the active site of cyclooxygenase-1 in platelets, inhibiting formation of thromboxane A2 from arachidonic acid. Vane was awarded the Nobel Prize 10 years later because he was the first to explain why aspirin might have net benefits in the treatment and prevention of CVD. So we have to remember that it's relatively recently in the history of aspirin that that mechanism has been described. When people say, "Don't use it at all," they are overinterpreting the risk for side effects, when in fact what we should be telling healthcare providers is that appropriate use requires an informed clinical judgment because that professional knows more than anyone about balance of benefits and risks for each of his or her particular patients.
Medscape: So how should the assessment as to whether a patient needs aspirin as primary prevention best be made?
Dr Hennekens: Way back when I participated in the first guidelines for aspirin, we said then what I still believe is true now: Look at the absolute risk for a CV event for the patient. If the absolute risk in a patient is high, then that patient will have a net benefit from aspirin; if it is low, then the patient might not have an absolute benefit. It is also necessary to evaluate the absolute risk for side effects for the patient, which is mainly extracranial bleeding, primarily gastrointestinal. We don't have enough evidence to know exactly where the dividing line is, so we will leave it to the judgment of the clinician until the ongoing trials are completed. I'm not in agreement with all of the complicated algorithms that clinicians are told to follow; I think that nobody knows more about the benefit and risk for the patient than his or her clinician, whose judgment should be based on the totality of evidence.
For example, the Framingham Risk Score (FRS) is often used as the basis for calculating the risk to a patient. It is a very good tool, developed to help categorize high, medium, and low. The FRS is based on data from the landmark Framingham Heart Study, a prospective cohort study of largely middle-class white people. Thus, a black or Hispanic patient is going to be at higher absolute risk than that predicted by their FRS. In addition, obesity and physical inactivity are also major risk factors for occlusive events, but they are not included in the risk score. Last but not least, you find that no matter what the risk factor score is, people with a positive family history—by which I mean an event in a man younger than 55 years and in a woman younger than 65 years—have about double the risk for CVD, independent of other risk factors.
Thus, my message to the clinician is: Don't rely on any calculator to help you decide a patient's risk. Look at the totality of evidence about your patient and weigh the absolute risk for an occlusion against the absolute risk for a bleed with aspirin. In the next few years the data will speak for themselves because we will have some tens of thousands of randomized subjects at intermediate and high risk in primary prevention. Right now, the evidence is incomplete, so until that happens, let's leave it at individual judgment and weigh the absolute benefit against the absolute risk for individual patients. The overall message should be: Don't give aspirin to people who don't need it, and don't withhold it from people who would benefit.
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Cite this: Does Aspirin Prevent Cardiovascular Disease and Cancer? Ignore the Guidelines - Medscape - Oct 29, 2014.