In July 2011, the FDA approved ticagrelor (Brilinta) as a blood-thinner for acute coronary syndrome patients. Both before and since then, experts and frontline clinicians have been discussing why this selective P2Y12-receptor antagonist did not show, in the PLATO randomized comparison with clopidogrel, a significant advantage in North American participants — even though it showed a benefit in the overall trial and in non-U.S. participants. Some have wondered whether relatively higher doses of aspirin used in the U.S. might be the problem and, therefore, that such doses should be “avoided” by users of ticagrelor. However, there is a very simple alternative theory:

Intermediate-dose aspirin is just plain more effective than low-dose aspirin. Therefore, ticagrelor provides no additional benefit when intermediate-dose aspirin is being used.

Take a look at the “ancient” aspirin trials, in which relatively higher doses of aspirin were often associated with outcome benefits despite more gastrointestinal bleeding. Many physicians do not know — or maybe just forgot — that some early trials showing a significant benefit of aspirin were done with 1300 mg daily! I’m not suggesting doses on that scale, but rather 162 mg to 325 mg daily, which also showed benefits in early studies.

Anecdotally, we seem to see a lot less GI bleeding nowadays, as the early studies were conducted before routine use of H2-receptor antagonists and proton-pump inhibitors. Given that some patients have aspirin resistance and there is a dose-response curve (albeit nonlinear), it makes sense that some subgroups may benefit from intermediate-dose aspirin (just as we explore whether some patients benefit from higher doses of clopidogrel).

The proper message may not be to “avoid tigacrelor” if you take intermediate-dose aspirin. Perhaps you just don’t need ticagrelor in the first place because aspirin’s already doing the job. Yes, this goes against the ACCF/AHA guidelines, but that’s what blog posts are for.

What do you think about my intermediate-dose aspirin theory? Please chime in.