METHODS: We used a matched case-control design using the Virtual International Stroke Trials Archive (VISTA). Cases were patients who had an acute coronary syndrome, recurrent stroke or transient ischaemic attack within 90 days post-stroke and were matched for age ± 10 years and sex with up to four controls. Antiplatelet use was categorized as persistent (used for >3 days and continued up to day 90), early cessation (used antiplatelet <3 days) or stopped/interrupted users (used for >3 days but stopped prior to day 90). These categories were compared in cases and controls using a conditional logistic regression model that adjusted for potential confounders.
RESULTS: A total of 970 patients were included, of whom 194 were cases and 776 were matched controls. At 90 days, 10 cases (5.2%) and 58 controls (7.5%) stopped/interrupted their antiplatelet. The risk of cardiovascular event was not different in stopped/interrupted users (adjusted odds ratio 0.70, 95% confidence interval 0.33, 1.48; P = 0.352) and early cessations (adjusted odds ratio 1.04, 95% confidence interval 0.62, 1.74; P = 0.876) when compared to persistent users.
CONCLUSION: We found no increased risk in patients who stopped and interrupted antiplatelets early after stroke but the study was limited by a small sample size and further research is needed.
STUDY QUESTION: Whether FDA death data in the PLATO trial matched the local site records.
STUDY DESIGN: The NDA spreadsheet contains 938 precisely detailed PLATO deaths. We obtained and validated local evidence for 52 deaths among 861 PLATO patients from 14 enrolling sites in 8 countries and matched those with the official NDA dataset submitted to the FDA.
MEASURES AND OUTCOMES: Existence, precise time, and primary cause of deaths in PLATO.
RESULTS: Discrepant to the NDA document, sites confirmed 2 extra unreported deaths (Poland and Korea) and failed to confirm 4 deaths (Malaysia). Of the remaining 46 deaths, dates were reported correctly for 42 patients, earlier (2 clopidogrel), or later (2 ticagrelor) than the actual occurrence of death. In 12 clopidogrel patients, cause of death was changed to "vascular," whereas 6 NDA ticagrelor "nonvascular" or "unknown" deaths were site-reported as of "vascular" origin. Sudden death was incorrectly reported in 4 clopidogrel patients, but omitted in 4 ticagrelor patients directly affecting the primary efficacy PLATO endpoint.
CONCLUSIONS: Many deaths were inaccurately reported in PLATO favoring ticagrelor. The full extent of mortality misreporting is currently unclear, while especially worrisome is a mismatch in identifying primary death cause. Because all PLATO events are kept in the cloud electronic Medidata Rave capture system, securing the database content, examining the dataset changes or/and repeated entries, identifying potential interference origin, and assessing full magnitude of the problem are warranted.