High-Dose Aspirin After Primary PCI Increases Bleeding with No Ischemic Benefit


Patients with ST-segment myocardial infarction (STEMI) who are discharged on high maintenance dose aspirin have similar long-term rates of adverse ischemic events but are more likely to experience major bleeding compared with similar patients on low-dose aspirin, according to an analysis from the HORIZONS-AMI trial published online December 17, 2012, ahead of print in JACC: Cardiovascular Interventions.

Researchers led by Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), compared 3-year outcomes in STEMI patients enrolled in the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial who were prescribed high-dose (> 200 mg daily; n = 562) or low-dose (≤ 200 mg daily; n = 2,289) aspirin following PCI with Taxus Express paclitaxel-eluting stents (Boston Scientific, Natick, MA) or Express bare-metal stents (Boston Scientific). All patients also received a 75-mg maintenance dose of clopidogrel for at least 6 months.

Higher Dose Predicts Major Bleeding

After propensity score-adjusted multivariable analysis, patients discharged on high-dose aspirin had higher 3-year rates of non-CABG–related major bleeding but similar rates of MACE (death, reinfarction, clinically driven TVR, and stroke) compared with patients on low-dose aspirin (table l).

Table 1. Adjusted 3-Year Outcomes

 

High Dose
(n = 562)

Low Dose
(n = 2,289)

P Value

MACE

20.5%

18.0%

0.41

Non-CABG Major Bleeding

4.5%

1.6

0.008


After adjustment, high-dose aspirin was as an independent predictor of non-CABG–related major bleeding (HR 2.80; 95% CI 1.31-5.99; P = 0.008) but not of adverse ischemic outcomes (HR 1.14; 95% CI 0.83-1.56; P = 0.41). The increase in major bleeding in the high-dose group emerged in the first 2 months after hospital discharge, although excess events continued to accrue with high-dose aspirin over the entire 3-year follow-up.

There was no interaction between enrollment within vs. outside the United States and aspirin dose on ischemic and bleeding endpoints, nor was there any significant effect of the duration of thienopyridine use on risk of major bleeding with high-dose vs. low-dose aspirin (P = 0.63).

Previous Studies Inconsistent

The authors say the data contribute “to an increasing literature that suggests that patients with ACS (both STEMI and non-STEMI) and those undergoing PCI should be maintained on low-dose rather than high-dose aspirin.”

Although other studies, including CURE and BRAVO, also have shown increased rates of bleeding at long-term follow-up with higher maintenance doses of aspirin, CURRENT OASIS 7, a large meta-analysis, showed no such difference in the 30-day rates of major bleeding or MACE in the overall cohort or the prespecified subgroup treated with PCI. All patients in that trial, however, received an aspirin loading dose of at least 300 mg, which Dr. Mehran and colleagues say may have diminished the ability for differences to emerge given the short follow-up duration.

In light of these conflicting results, current consensus guidelines, issued in 2011, say that it is reasonable to use 81 mg/day maintenance aspirin dose instead of higher doses.

The HORIZONS-AMI researchers acknowledge that their analysis is exploratory and only a large-scale, randomized trial can definitively address the issue of appropriate aspirin dose. Nonetheless, they add, “absent a demonstrated benefit of high-dose aspirin in patients on dual antiplatelet therapy with clopidogrel following PCI, and given the concern of potential harm of high-dose aspirin used with more potent P2Y12 inhibitors (ie, prasugrel and ticagrelor), these data support the routine use of low-dose aspirin . . . at discharge following primary PCI in STEMI.”

Study Details

Patients discharged on high-dose rather than low-dose aspirin were more likely to have a history of hypertension, hyperlipidemia, family history of premature coronary disease, or prior treatment with PCI or CABG, and to be enrolled in the United States.

Note: Dr. Mehran and several coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 


Source:
Yu J, Mehran R, Dangas GD, et al. Safety and efficacy of high- versus low-dose aspirin after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: The HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. J Am Coll Cardiol Intv. 2012;Epub ahead of print. 

 

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Disclosures
  • The HORIZONS-AMI trial was funded by Boston Scientific and The Medicines Company.
  • Dr. Mehran reports serving as a consultant to Abbott Vascular, AstraZeneca, Johnson & Johnson, Maya Medical, and Merck Sharp & Dohme; serving on the advisory board of Regado; and receiving research grants from BMS/Sanofi, Daiichi-Sankyo/Eli Lilly, and The Medicines Company.

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