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Phase III head-to-head trial showed ticagrelor reduced cardiovascular death and heart attacks over clopidogrel in acute coronary syndromes patients

AstraZeneca recently announced results from the Phase III head-to-head trial PLATO that demonstrate that ticagrelor has achieved greater efficacy in the primary endpoint, reduction of cardiovascular events, than clopidogrel.

The results from A Study of Platelet Inhibition and Patient Outcomes (PLATO) have demonstrated that ticagrelor (BRILINTA™) has achieved greater efficacy in the primary endpoint, reduction of cardiovascular events (CV death, myocardial infarction and stroke), than clopidogrel (Plavix®/Iscover®) (9.8% vs 11.7% at 12 months; 16% RRR; 95% CI, 0.77 to 0.92; p<0.001), without an increase in major bleeding (11.6% vs 11.2%, p = 0.43). This efficacy endpoint was driven by a statistically significant reduction in both CV death (4.0% vs 5.1%, p = 0.001) and myocardial infarction (5.8% vs 6.9%, p = 0.005) with no difference in stroke (1.5% vs 1.3%, p = 0.22). Primary results from the PLATO study were presented at the European Society of Cardiology congress and simultaneously published in the New England Journal of Medicine.

For patients in the PLATO study, the reduction in risk of cardiovascular events with ticagrelor occurred early, and this benefit increased over time compared with clopidogrel. Ticagrelor demonstrated a consistent positive effect across multiple secondary efficacy endpoints, including CV death (and separately for all-cause mortality); myocardial infarction; and the composite of myocardial infarction, stroke, and all-cause mortality. Among patients who received a stent during the study, a 33% reduction in risk of definite stent thrombosis was achieved with ticagrelor.

PLATO was an international head-to-head 18,624 patient outcomes study of ticagrelor plus aspirin, versus clopidogrel plus aspirin. The PLATO study was designed to establish whether ticagrelor could achieve clinically meaningful cardiovascular and safety endpoints in ACS patients, above and beyond those afforded by clopidogrel, an irreversible therapy in the thienopyridine class of medicines.

The PLATO study confirmed the clinical safety profile of previous ticagrelor studies, which showed no difference in major bleeding compared to clopidogrel. When minor bleeding was added to the major bleeding results, ticagrelor showed an increase versus clopidogrel (16.1% vs 14.6%, p = 0.008). There was also an increase in non-procedural related bleeding with ticagrelor.

PLATO analyzed 66 subgroups (33 efficacy and 33 safety subgroups). Thirty of the 33 efficacy subgroups analyzed were consistent with the analysis of efficacy in the overall population, showing a benefit for ticagrelor over clopidogrel. Of the three remaining subgroups, one (patients with weight below the gender-specific median) showed an attenuated benefit for ticagrelor over clopidogrel. The other two subgroups (patients not taking a statin medication on the day of randomization and those at sites in North America) showed no treatment advantage for ticagrelor.

Of the 33 safety subgroups analyzed, 32 were consistent with the analysis of safety in the overall population; showing no statistically significant difference between ticagrelor and clopidogrel. The remaining subgroup (patients with a Body Mass Index >30kg/m2) had major bleeding more frequently with ticagrelor than with clopidogrel.

Ticagrelor (BRILINTA) is an investigational oral antiplatelet treatment for ACS. BRILINTA is the first reversibly binding oral adenosine diphosphate (ADP) receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP. ADP receptor blockade inhibits the action of platelets in the blood, reducing recurrent thrombotic events. BRILINTA is the first in a new chemical class, the CPTPs (cyclo-pentyl-triazolo-pyrimidines) and is chemically distinct from the thienopyridines, such as clopidogrel and prasugrel.

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