Document Classification

Section Type: RESULTS

Text: FDA Medical Review indicated that (1) patients on ticagrelor monitored by the study sponsor had a lower odds ratio for the primary endpoint (p = 0. 0004) versus ticagrelor patients monitored by a third party Clinical Research Organisation (CRO) independent of the study sponsor, (2) a significant interaction existed between ticagrelor and regions monitored by the study sponsor for all cause mortality through study end in favor of ticagrelor (p = 0. 006), (3) ticagrelor faired worse than clopidogrel when regions were monitored independent of the study sponsor by a third party Contract Research Organisation (United States, Russia and Georgia), (OR = 1. 21, 95 % CI : 0. 91 to 1. 59, p = 0. 2022), (4) 46 % of all primary endpoint events favoring ticagrelor came from just two countries (Poland and Hungary), (5) PLATO was easy to unblind by breaking open a clopidogrel/dummy clopidogrel tablet with at least 452 patients being unblinded prior to the database lock, (6) significantly more cardiac events submitted for clopidogrel counted in the primary analysis as a myocardial infarction (MI) compared to those submitted for ticagrelor (p < 0. 0001), (7) significantly more ticagrelor subjects hospitalized after an index event/hospitalization were not being reported as having a primary event compared to clopidogrel (p = 0. 002 in favor of ticagrelor), (8) site-reported MI was not significantly reduced with ticagrelor versus clopidogrel, (9) an estimated 23 definite or possible cardiovascular events or deaths on ticagrelor were either not submitted for adjudication, inactivated, deleted or were downgraded to '' softer '' endpoints (this was not shown in the FDA review for clopidogrel), and (10) four FDA reviewers voted for non-approval of ticagrelor.