Prasugrel Superior to Ticagrelor in Acute Coronary Syndromes

Commentary

Dual antiplatelet therapy combining an adenosine disphosphate (ADP) receptor antagonist and aspirin is standard treatment for patients presenting with ACS. The limitation of clopidogrel has been its modest antiplatelet effect, with substantial interpatient variability. The newer generation thienopyridine prasugrel and the reversible direct-acting oral antagonist of the ADP receptor ticagrelor provide consistent and greater antiplatelet effect compared to clopidogrel. It has been previously reported that these agents are superior in reducing ischemic events when compared to clopidogrel.^1,2 Therefore, current guidelines recommend ticagrelor and prasugrel in preference to clopidogrel.^3,4 However, there has been no large randomized controlled study comparing the effect of ticagrelor and prasugrel. In this context, Shupke et al investigated this clinical question by performing a well-designed multicenter randomized controlled trial in patients presenting with ACS. At 12-month follow-up, the composite of death, myocardial infarction, and stroke occurred more frequently in the ticagrelor group compared to the prasugrel group (9.3% versus 6.9%; HR, 1.36; 95% CI, 1.09-1.70; P < 0.01). The incidence of major bleeding was not significantly different between the 2 groups (5.4% versus 4.8%; P = 0.46).

The strengths of this current study include the randomized design and the large number of patients enrolled, with adequate power to evaluate for superiority. This was a multicenter trial in Europe with 23 participating centers (21 from Germany). Furthermore, the interventional technique used by the operators reflects more contemporary technique compared to the previous studies comparing each agent to clopidogrel,^1,2 with more frequent use of radial access (37%) and drug-eluting stents (90%) and reduced use of GPIIb/IIIa inhibitors (12%).

There are a few important points to consider due to the differences between the 2 agents compared in this study. First, the loading dose of ticagrelor and prasugrel was administered differently in patients presenting with ACS without ST elevation. Ticagrelor was administered as soon as possible prior to the coronary angiogram, but prasugrel was administered after the coronary anatomy was defined prior to the intervention, which is how this agent is administered in current clinical practice. Therefore, this trial was an open-label study that compared not only different medications, but different administration strategies. Second, ticagrelor and prasugrel have different side-effect profiles. The side effects unique to ticagrelor are dyspnea and bradycardia. On the other hand, a contraindication unique to prasugrel is patients with a history of transient ischemic attack or stroke due to increased risk of thrombotic and hemorrhagic stroke.¹ In addition, prasugrel has increased bleeding risk in patients older than 75 years of age and those with low body weight (< 60 kg). In this study, the overall medication discontinuation rate was higher in the ticagrelor group specifically due to dyspnea, and the reduced dose of 5 mg of prasugrel was used in patients older than 75 years or with low body weight.

Since the timing of administration of ticagrelor (preloading prior to coronary angiography is recommended) is similar to that of clopidogrel, and given the theoretical benefit of reversible inhibition of the ADP receptor, ticagrelor has been used more commonly in clinical practice than prasugrel, and it has been implemented in the ACS protocol in many hospitals. In light of the results from this first head-to-head comparison utilizing more contemporary interventional techniques, these protocols may need to be adjusted in favor of prasugrel for patients presenting with ACS. However, given the difference in timing of administration and the difference in side-effect profile, operators must also tailor these agents depending on the patient profile.

Applications for Clinical Practice

In patients presenting with ACS, prasugrel was superior to ticagrelor, with a lower composite of death, myocardial infarction, and stroke at 12 months. Prasugrel should be considered as a first-line treatment for ACS.

– Taishi Hirai, MD, and Arun Kumar, MD, University of Missouri, Columbia, MO