Читать книгу Interventional Cardiology - Группа авторов - Страница 319

Prasugrel, like clopidogrel, is a prodrug, however, it has a significantly shorter metabolic pathway, allowing for a faster and more complete inhibition of platelet aggregration [42]. The seminal TRITON‐TIMI study [43], included 3534 patients with STEMI, and showed a significant benefit of prasugrel compared to clopidogrel overall, and particularly in the STEMI cohort (hazard ratio for primary efficacy end point of death from cardiovascular causes, nonfatal MI, or non‐fatal stroke 0.79; 95% CI 0.65–0.97; p = 0.02). The Elderly ACS 2 Trial assessed the efficacy and safety of prasugrel vs clopidogrel in the >74 year old ACS population in general, but STEMI patients made up 42% of cases [44]. Overall, and in particular in the STEMI cohort, there was no difference detected in a primary endpoint of all‐cause mortality, MI, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within one year (HR 1.00; 95% CI 0.68–1.47; p = 0.99 for the STEMI cohort).

In terms of the timing of prasugrel administration, particularly in contrast to recently published data for patients presenting without persistent ST‐segment elevation, it should be noted that there exists no clear evidence with regard to whether early upstream administration of prasugrel for STEMI patients leads to better outcomes compared to on table administration. One study, however, involving 328 consecutive patients presenting with STEMI, 46% of whom were administered prasugrel, assessed pre‐ and post‐PCI TIMI flow grade stratified by time of P2Y12 inhibitor administration prior to intervention [45]. Those that had a P2Y12 inhibitor administered >60 mins prior to PCI appeared to have better TIMI flow pre‐ and post‐PCI, and better resolution of ST segment elevation. However, this study was not powered to assess hard clinical endpoints.

In terms of the mode of administration, it has been shown that crushed prasugrel is better absorbed than integral prasugrel, but this has not been shown to correlate with better clinical outcomes. In the FABOLUS FASTER trial [46], chewed prasugrel, despite yielding higher active metabolite concentration, did not provide higher inhibition of platelet activity (IPA) over integral prasugrel. In the COMPARE CRUSH trial [47], 727 STEMI patients were assigned to a loading dose of either crushed or integral prasugrel. Results revealed a significantly decreased proportion of patients with high platelet reactivity at the beginning of primary PCI with crushed tablets, but this did not translate into significant differences in TIMI 3 flow in the IRA at initial angiography (OR 0.92, 95% CI 0.65–1.30; p = 0.64 for the crushed group), or the proportion of patients with complete ST‐segment resolution one hour post primary PCI (OR 1.11, 95% CI 0.78–1.58; p = 0.55) [48].

Ticagrelor

The PLATO randomized trial compared ticagrelor to clopidogrel for the prevention of cardiovascular events in patients admitted to hospital with acute coronary syndrome [49]. Just under 38% of the total population enrolled in the study presented with STEMI, and in a subgroup analysis, the hazard ratio for a primary endpoint of CV death/MI or stroke was 0.87 (95% CI 0.75–1.01; p = 0.07). This arises from an 18% relative reduction in the composite of MI and cardiovascular mortality but an increase in the rate of (non‐hemorrhagic) stroke. There was no significant increase in major bleeding overall.

In contrast to prasugrel, there have been several studies looking at the optimal timing of administration of ticagrelor. The Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery (ATLANTIC) study looked at a cohort of 1862 patients who were either administered prehospital (in the ambulance) versus in‐hospital (in the cath lab) ticagrelor, with a median time difference between the two treatment strategies of only 31 minutes [50]. There was no significant difference between the degree of ST‐segment element resolution or proportion of patients with TIMI III flow in the IRA. There was, however, a close to significant reduction in acute, definite stent thrombosis (0 vs 8 cases, p = 0.055). Rates of major bleeding were virtually identical in both groups. A study assessing 7433 patients, through the SWEDEHEART registry, who presented with acute STEMI and were either pretreated with ticagrelor, or given it only in the catherization lab, revealed no difference in a composite endpoint of mortality, MI or stent thrombosis [51].