Sunday, January 13, 2008

Is Your Aspirin Resisting You?

Like most of you I take aspirin daily, 325mg. Even traditional cardiologists recommend aspirin for heart disease sufferers. Aspirin works by interfering with the generation of thromboxane A2 (TXA2) which is needed for platelet aggregation (clotting). The COX-1 enzyme acts on arachidonic acid (AA) to produce endoperoxides that in turn produce TXA2 . Aspirin interferes with the generation of TXA2 by irreversably acetylating the platelet COX-1 enzyme thereby blocking its access to AA. Because platelets are anucleate, they cannot generate additional COX-1. In the absence of TXA2, platelet aggregation does not occur. Got all that?!

Most practitioners prescribe anywhere from 81mg to 325mg. Studies such as CURE suggest 81mg is optimal. The ISIS-2 study puts the dose at 162mg (for recent heart attack sufferers) and, frankly, since aspirin is so cheap, many (like me) simply make the leap to "more must be better." Ahh, but there are downsides to higher dose aspirin, among them bleeding and stomach problems (me again). But there is another dosing consideration, aspirin resistance, a reduced response to aspirin that one study suggests affects 27% of the general population.

Once again, like many of you, I am also a Track Your Plaque convert (see my early posts and disclaimers). As a numbers geek it appeals to me to have hard data to track and make intelligent decisions about controlling my heart disease. So the question those like me have is, "Is there any way to determine if I am aspirin resistant and if so, how resistant am I and how much aspirin do I need to take?" The biggest problem is that there is currently NO clinically valid definition or measurement of "aspirin resistance". However, here is the latest on available tests to provide some answers.

The PFA-100 is US Food and Drug Administration (FDA)-approved to detect platelet dysfunction, von Willebrand disease, and aspirin-induced platelet inhibition. The instrument measures collagen-induced platelet plug formation as time in seconds to occlude an aperture. Its sensitivity as a screen for platelet dysfunction is approximately 95%.

The VerifyNow Aspirin Assay is FDA-approved for detection of aspirin-dependent platelet aggregation. Its sensitivity as a screen for aspirin-induced platelet dysfunction is approximately 91%.

PlateletWorks is FDA-approved to detect platelet dysfunction due to inhibition secondary to diet, aspirin, and/or other drugs. PlateletWorks has limitations. There is a very short time allowed -- 10 minutes -- between sample collection and assay. Also, there may be unacceptably high false-positive rate because of interference by dietary substances such as chocolate and red wine.

AspirinWorks is FDA-approved to provide a quantitative measurement of aspirin-induced inhibition of TXA2 generation from a urine sample. Results are ranged in quartiles with different quartiles represent differing degrees of risk for heart attack. A patient whose results are in the first quartile has a relative risk 1 (average). A patient whose results are in the second quartile has a 1.3 times greater risk of heart attack than a patient in the first quartile. A patient whose results are in the third quartile has a 1.5 times greater risk, and a patient in the fourth quartile has twice the risk. As with many lipid tests, there are still problems to work out in comparing results based on different assay methods.

The bottom-line is there is no perfect way to determine to what degree you are aspirin resistant but the technology is improving. However, if you are looking for some way to put a hard number on where you stand there are several interesting tests available. For now, I simply take the high-end of the dose range until my tummy starts to hurt then take a break or reduce my dose.



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