- MeSH
- dieta s nízkým obsahem soli škodlivé účinky MeSH
- hypertenze prevence a kontrola MeSH
- krevní tlak MeSH
- kuchyňská sůl * MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
CONTEXT: Ticagrelor, a novel, reversible, and oral P2Y12 receptor antagonist, was claimed to reduce all-cause mortality compared to clopidogrel in the PLATO trial. OBJECTIVE: We sought to ascertain vital status follow-up for clopidogrel and ticagrelor to determine if any discrepancy existed by reviewing data from the FDA Complete Response Review. RESULTS: The FDA Complete Response Review indicated misrepresentation of vital status follow-up by the sponsor's presenter at the Cardiovascular and Renal Drugs Advisory Committee. Instead of five patients with missing vital status follow-up, the FDA primary efficacy reviewer indicated that there was a minimum of 106 patients. Additionally and more concerning was the fact that significantly more patients on ticagrelor (3.1%, n = 289 patients) had incomplete vital status follow-up versus clopidogrel (2.6%, n = 242 patients, p = 0.04 for the difference). CONCLUSIONS: The Advisory Committee that voted in favor to approve ticagrelor was given misrepresented data, which may have affected the approval of ticagrelor. The fact that significantly more patients on ticagrelor had incomplete vital status follow-up versus clopidogrel challenges the claimed mortality benefit of ticagrelor and the approval of the PLATO trial.
- MeSH
- adenosin škodlivé účinky analogy a deriváty terapeutické užití MeSH
- antagonisté purinergních receptorů P2Y terapeutické užití MeSH
- hodnocení rizik MeSH
- klinické zkoušky jako téma kontraindikace etika normy MeSH
- lidé MeSH
- mortalita trendy MeSH
- následné studie MeSH
- poradní výbory normy MeSH
- schvalování léčiv * MeSH
- statistika přirozeného pohybu MeSH
- tiklopidin škodlivé účinky analogy a deriváty terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
OBJECTIVE: Ascertain platelet inhibition and patient outcomes (PLATO) trial conduct. METHODS: We examined information from the FDA complete response review. RESULTS: 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. DISCUSSION: The FDA report highlights what appear to be multiple serious deficiencies in the reporting of the PLATO results, which clinicians will not have gleaned from the primary publication alone. Individual clinicians may therefore wish to carefully reconsider their practice of ticagrelor prescription for this indication. Guideline bodies should also evaluate the information in its totality.
- MeSH
- adenosin analogy a deriváty terapeutické užití MeSH
- akutní koronární syndrom diagnóza farmakoterapie epidemiologie MeSH
- antagonisté purinergních receptorů P2Y terapeutické užití MeSH
- inhibitory agregace trombocytů terapeutické užití MeSH
- lidé MeSH
- reprodukovatelnost výsledků MeSH
- stanovení cílového parametru metody normy MeSH
- Úřad Spojených států pro potraviny a léky normy MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Spojené státy americké MeSH
