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Prevalence of aspirin resistance

Systematic review
Results
Comment

Aspirin probably works by irreversibly inactivating cyclooxygenase-1 in platelets, which means that they cannot produce thromboxane A 2 with a consequent reduction in aggregation. It is worth noting that while NSAIDs also inhibit cyclooxygenase-1, this inhibition is reversible, and so any effect wanes as drug levels diminish, with only a transient reduction, if any, in platelet aggregation.

Aspirin resistance is a simple description of a complex phenomenon, namely the persistence of platelet aggregation despite use of aspirin. That simple statement is deceptive, however, because there is no agreed definition of aspirin resistance. A variety of laboratory tests are used to measure aspirin resistance.

So a moment's reflection demonstrates that trying to measure the prevalence of aspirin resistance is not going to be straightforward. Apart from differences between individuals (due to pharmacokinetic or genomic issues), there will be issues of dose of aspirin, co-medication, medical condition, as well as method of measurement and definition of resistance to contribute to differences in measured prevalence. All of which is made plain by a systematic review [1] that tries to pull some of this together.

Systematic review

The systematic review used a heroic series of searches to find studies. To be included a study had to report the prevalence of aspirin resistance from a survey or cohort study with consecutive patients, have a clear definition of aspirin resistance, in well described patients using aspirin for secondary prevention of cardiovascular events.

Stratified analyses were planned by dose of aspirin and laboratory method used to measure aspirin resistance, according to the populations studied (post myocardial infarction, stroke or TIA, and revascularisation, or other).

Results

The review included 34 full articles and eight abstracts, but we are not told the number of patients studied in total, the number of patients in each study, nor the prevalence in each study. All we have is a series of results of pooled analyses, and it is clear that some individual studies must have reported on more than one group of patents, dose of aspirin, and method of analysis.

Overall aspirin resistance was 24%, with prevalence in individual studies ranging from 0% to 57%. Figure 1 shows the 95% confidence intervals for prevalence of aspirin resistance according to aspirin dose, after some statistical adjustments. There was little difference in aspirin resistance prevalence between different patient groups, or by different methods of measurement, with one exception. Five studies using arachidonic acid as an agonist in light transmission aggregometry reported lower prevalence values of 1% to 12% (average 6%).



Figure 1: Prevalence of aspirin resistance (failure to inhibit platelet aggregation) with daily aspirin dose





Comment

It is a bit of a shame that there is some opaqueness about the review, and this is one of the times to bemoan the lack of accompanying tables with information on the individual studies. If they were there, we might do some sums of our own without retrieving 42 papers and starting from the beginning.

But that is a quibble stemming from the importance of the paper. The authors do their weighting based on patient numbers.

Perhaps the take-home message is that a prevalence of aspirin resistance of 1 person in 4 might be a worst-case scenario. For instance, we have the problems of definition and method, and it may well be that more conservative definitions and defined methods would reduce rather than increase the prevalence. Again, we have no idea about compliance: we know from other sources that compliance with daily aspirin is often poor, and that would certainly contribute to higher apparent aspirin resistance.

These are details that will be sorted out in due course. What we can be pleased about is that this should be the first step on the path of individualising therapy (perhaps measuring resistance after starting at very low doses of aspirin) and improving cardiovascular outcomes.

Reference:

  1. MM Hovens et al. Prevalence of persistent platelet reactivity despite use of aspirin: a systematic review. American Heart Journal 2007 153:175-181.

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