Ticagrelor, even better than we thought

Original title: Reduction in First and Recurrent Cardiovascular Events with Ticagrelor Compared with Clopidogrel in the PLATO Study. Reference: Payal Kohli et al. CIRCULATION AHA.112.124248.

In analyzing randomized and monitored study outcomes, we usually observe that after the occurrence of any primary outcome event patients are typically blocked for further analysis. 

This practice limits the information on subsequent events in patients that had already presented a non fatal event. This study assesses the effect of ticagrelor (a potent reversible antagonist of ADP P2Y12 receptor) compared to clopidogrel in recurrent events from the PLATO trial (PLATelet inhibition and patient Outcomes). 

The original PLATO study had already reported that ticagrelor reduces the composite of cardiovascular, infarction and stroke (HR 0.84, 95% CI 0.77-0.92, p<0.001) but this study follows up on patients that presented non fatal events. The risk of subsequent events was also significantly reduced by the use of ticagrelor (HR 0.80, 95% CI 0.70-0.90, p<0.001). There is more risk of multiple events in the elderly, diabetics, those with a history of infarction or myocardial revascularization, kidney failure or female patients.

Enrolled STEMI patients had less probabilities of presenting more events compared to non STEMI patients. As regards the safety end point, it was reported in the original PLATO study that ticagrelor increased the total number of bleeding events at the expense of less bleeding (HR=1.09, 95% CI 1.01-1.17, p=0.02), with no difference in subsequent bleeding events.

Conclusion 

Ticagrelor compared to clopidogrel in acute coronary syndromes reduces both the occurrence of first events and of subsequent events. This results in the need to deal with an even smaller number.

Editorial Comment:

This analysis, despite its limitations, has important clinical implications. Ticagrelor, more potent than clopidogrel, presents a higher risk of bleeding; therefore, when treating a hemorrhagic patient that has received ticagrelor we could be tempted to switch to clopidogrel. However, this study did not show a higher risk of subsequent bleeding, so switching would only deprive our patient of the benefit of a reduction in ischemic events.

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