Wednesday, October 5, 2011

CURRENT-OASIS 7: finally time to abandon high-dose aspirin?

Much of the press garnered by the CURRENT-OASIS 7 trial has focused on the comparison of double-dose and standard-dose clopidogrel in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes. The subgroup of patients who actually went to PCI had better outcomes with double-dose clopidogrel, a result that was largely driven by a reduction in recurrent myocardial infarction (MI) and stent thrombosis. Although there was little risk associated with double-dose clopidogrel, the practice only made its way into the 2011 guidelines as a Class IIb recommendation and has not really caught on here at our institution.

Clopidogrel aside, I feel one of the more compelling aspects of the trial was the comparison of high and low-dose aspirin. All patients were initially loaded with high-dose aspirin but were then randomized to receive high-dose (> 300 mg) or low-dose (< 100 mg) aspirin for the remainder of the trial. As expected, there were no differences in efficacy between the two arms... but surprisingly, there were no differences in the rates of bleeding either.

The results of the aspirin analysis in CURRENT-OASIS 7 only reinforce what observational data have suggested for some time -- that higher doses of aspirin are unlikely to provide any additional benefit after an initial loading dose. However, in North America, we tend to use higher doses of aspirin than our counterparts in the rest of the world. (This is thought to be a possible explanation for the North American anomaly seen in the PLATO trial, where patients in North America who received ticagrelor actually did worse than patients across the globe).

With our understanding that the bleeding risk of aspirin is dose-related -- and now with prospective data showing no advantages with the higher dose -- it is surprising that we have not been more proactive in using lower doses here in the US. In fact, while the 2011 guidelines recognize the results of the CURRENT-OASIS 7 trial, they still recommend using higher doses for a period of time in most patients. I recognize that, for the purposes of making it a stronger recommendation, we probably need more data from randomized controlled trials, but these results seem to only confirm something that has been suspected for a long long time (and what many of our European counterparts are already doing).

So, is it time to finally abandon the practice of using high-dose aspirin in patients who receive an appropriate initial loading dose? I think CURRENT-OASIS 7 tells us yes... but until the guidelines change significantly, I imagine many of us here in the US will still feel compelled to use higher dose aspirin for some length of time after an acute coronary event.

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