Bleeding, No Extra Ischemic Protection With High-Dose Aspirin


December 19, 2012

An analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial has shown that patients with ST-segment-elevation MI (STEMI) undergoing primary PCI discharged on high-dose aspirin have higher rates of major bleeding than those discharged on low-dose aspirin. The high-dose aspirin also failed to provide any additional protection against ischemic events [1].

"In the clinical guidelines, the recommended dose of aspirin ranges anywhere from 82 mg to 325 mg because we don't really have any prospective, randomized study showing which dose is actually best for these patients, which is kind of interesting given that we are now putting so much of our attention on the bleeding complications," Dr Roxana Mehran (Mount Sinai School of Medicine, New York), one of the study authors, told heartwire . "I think it's important that agents not only protect you against ischemia but also don't expose you to the harm of bleeding complications."

The HORIZONS-AMI analysis, published in the December 2012 issue of JACC: Cardiovascular Interventions, compared three-year outcomes among 2289 patients discharged on low-dose aspirin (≤200 mg/day) and 562 patients treated with high-dose aspirin ( > 200 mg/day). The analysis is a post hoc one, however, and subject to the possibility of confounding associated with such reports. For example, patients discharged on high-dose aspirin were more likely to undergo femoral PCI (vs radial) and had longer stents implanted, longer fluoroscopy times, and more contrast volume, as well as shorter symptom onset and door-to-balloon inflation times.

"The intriguing finding we found in this study was that the high-dose aspirin did not provide any benefit in terms of ischemic protection and exposed the patient to more risk," said Mehran. "Now, having said that, there are some limitations attached to this, as this was not a randomized, prospective clinical trial. The dosing of aspirin was the not the intent of the HORIZONS-AMI study. Therefore, it is subject to unmeasured confounders, and we already know there was a big difference in the patients prescribed high-dose aspirin and those given low-dose aspirin."

That said, the researchers adjusted for these baseline patient characteristics and showed in a propensity-score-adjusted multivariate analysis that discharge on high-dose aspirin was associated with a nearly threefold increased risk of major bleeding (hazard ratio 2.80; 95% CI 1.31–5.99). The increase in major bleeding occurred within the first two months following hospital discharge but continued to increase over the entire three-year follow-up period. High-dose aspirin was not associated with a reduction in any ischemic events.

"Once again, the moral of the story is that we really need to pay a lot of attention to the level of risk of our STEMI patients, understanding that these patients are at risk of bleeding and ischemic complications," said Mehran. "We have to balance that, and that balance may very well include making sure we choose the right dose of aspirin depending on their risk of bleeding."

Mehran noted that the HORIZONS-AMI study did not use the more potent antiplatelet agents, such as ticagrelor (Brilinta, AstraZeneca) or prasugrel (Effient, Lilly), but with these agents available to clinicians there is an increased need to focus on using lower-dose aspirin. There is also a need for randomized, prospective trials evaluating different doses of aspirin on discharge in patients with STEMI, non-STEMI, and unstable angina, she added.