Platelet Inhibition Faster With Prasugrel vs Clopidogrel

Excelsior LOAD trial results suggest platelet inhibition occurs twice as fast with prasugrel 60 mg compared with clopidogrel in stable patients undergoing percutaneous coronary intervention.

In stable patients undergoing percutaneous coronary intervention (PCI), prasugrel 60 mg produced stronger platelet inhibition than clopidogrel loading, and was associated with an onset of platelet inhibition twice as fast as clopidogrel, according to results of the Excelsior LOAD trial.

Investigators randomly assigned 300 P2Y12-receptor blocker-naïve patients undergoing elective PCI to either clopidogrel 600 mg, prasugrel 30 mg, or prasugrel 60 mg just prior to PCI.

Patients aged 18 years or older with obstructive coronary heart disease and planned coronary stent implantation pretreated with aspirin were enrolled at the University Heart Center in Bad Krozingen, Germany, from June 2014 to March 2015. All patients were treated with aspirin 100 mg and clopidogrel 75 mg daily for at least 30 days following coronary intervention.

The primary end point was the proportion of patients with high on-treatment platelet reactivity at 60 minutes after loading, defined as ≥468 AU per minute.

High on-treatment platelet reactivity was observed in 33% of patients assigned to prasugrel 60 mg, 37% of those assigned to prasugrel 30 mg, and 55% of those assigned to clopidgrel 600 mg (P<.001). Significant results were seen in the predefined comparisons: clopidogrel 600 mg vs prasugrel 60 mg (P<.001); clopidogrel 600 mg vs prasugrel 30 mg (P=.008); and prasugrel 30 mg vs prasugrel 60 mg (P=.024). Prasugrel 30 mg was associated with a higher response compared with clopidogrel 600 mg, but only at 30 and 60 minutes after loading.

At 60 minutes, platelet reactivity with prasugrel was not significantly different than at 120 minutes with clopidogrel (P=.18). In addition, bleeding event incidence at 30 days was not different among the 3 groups.

“Current guidelines list loading with prasugrel as an option by expert opinion for specific high risk situations of elective stenting,” researchers noted. “However, data on the very early antiplatelet effect, which reflects the time of coronary intervention and therefore of highest risk of ischemic complications, and in particular in stable patients were sparse.”

One of the trial’s key features was the inclusion of a lower loading dose of prasugrel 30 mg. “Such a lower loading dose can achieve a stronger antiplatelet effect as compared to clopidogrel and might be beneficial with respect to bleeding risk compared to loading with prasugrel 60 mg as demonstrated in previous studes.”

Investigators encouraged further evaluation of prasugrel loading followed by clopidgrel maintenance therapy in patients with stable disease in a prospective outcome trial.


Hochholzer W, Amann M, Titov A, et al. Randomized comparison of different thienopyridine loading strategies in patients undergoing elective coronary intervention. JACC Cardiovasc Interv. 2016. doi:10.1016/j.jcin.2015.10.036.