Original title: Comparison of Prasugrel and Ticagrelor loading doses in STEMI patients: The Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI Study. Reference: Guido Parodi et al. J Am Coll Cardiol 2013. Article in press.

Current guidelines recommend the use of prasugrel or ticagrelor in patients with ST elevation acute coronary syndromes who are due to receive primary angioplasty. 

A quick start for both prasugrel and ticagrelor could maximize the effect of bivalirudin and potentially reduce the risk of acute stent thrombosis. However, because the loading dose in both drugs has only been measured in healthy volunteers or in stable coronary patients, pharmacodynamics give this as the reason why this study was designed to compare the action of prasugrel and ticagrelor in patients having a myocardial infarction after primary angioplasty and bivalirudin as mono-therapy.

The RAPID study randomized 50 patients with a 60 mg loading dose of prasugrel or 180 mg of ticagrelor. The load was administered as soon as possible in the emergency department or in the catheterization room concomitantly with aspirin and bivalirudin. The use of heparin was discouraged and the glycoprotein inhibitors IIBIIIA were prohibited. Platelet reactivity was measured at the time of load reception and then at two, four, eight and twelve hours with VerifyNow®. We defined high residual platelet reactivity as a value of ≥ 240 PRU, (platelet reactivity units). The primary end point was the residual platelet reactivity after two hours of charging. 

36% of patients received the loading dose in the emergency department and 64% in the catheterization room. At two hours of load, platelet reactivity was 242 PRU, half without differences between prasugrel and ticagrelor, (217 PRU versus 275 PRU respectively, p = 0.207). Prasugrel was not inferior to ticagrelor to inhibit platelet activity at two hours of charging. The median time to reach a residual platelet reactivity

Conclusion: 

In patients having ST-segment elevation with acute coronary syndrome and who received primary angioplasty with bolus and bivalirudin infusion, prasugrel was not inferior to ticagrelor in terms of residual platelet reactivity after two hours of charging. Both drugs provided effective platelet inhibition to two hours in only half of the patients; most of them required at least four hours.

Commentary: 

While we have to confirm that these results will translate into clinical events, both drugs, in terms of residual platelet reactivity after two hours, still only ensured results within an acceptable range in only half of the patients. With this delay in action, the charge should be administered immediately after diagnosis to avoid the waiting time while the patient is going to the catheterization room. Perhaps the oral route is the Achilles heel of these drugs and cangrelor can fix the problem but it will take time to know the answer because the effectiveness of cangrelor has not yet been tested against prasugrel or ticagrelor. Moreover, the striking delay in the effect for those who received morphine could be explained because the decrease in motility caused by gastro-intestinal opioid is associated with a slower absorption of antiplatelet. 

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