Impact of the reporting source on Platelet Inhibition and Treatment Outcomes (PLATO) trial deaths.

Background: Platelet Inhibition and Clinical Outcomes (PLATO) was a multicenter, randomized double-blind trial assessing efficacy and safety of ticagrelor versus clopidogrel in patients with acute coronary syndrome. The reported mortality benefit of ticagrelor in the PLATO trial has been challenged for over decade, and never confirmed in later trials.

Objective: To compare if there were any differences when deaths were reported to the FDAby the sponsors or by independent Contract Research Organizations (CRO).

Strokes and Transient Ischemic Attacks Occurrence During Annual Dual Antiplatelet Therapy.

Background: The incidence of stroke/TIA during annual dual antiplatelet therapy (ADAPT) for acute coronary syndrome (ACS) remains high. Some evidence suggests that shorter than ADAPT may diminish such risk, still providing adequate vascular protection. However, the precise timing of strokes/TIA occurrences during ADAPT is unclear but may be important for determining optimal preventive treatment duration.

Adjunctive Cilostazol in Patients With High Residual Platelet Reactivity After Drug-Eluting Stent Implantation: A Randomized, Open-Label, Single-Center, Prospective Study (ADJUST-HPR).

Background: Cilostazol as an adjunct to dual antiplatelet therapy (DAPT) postcoronary stenting may further reduce vascular occlusion risks. The aim of this study was to assess the impact of cilostazol on high residual platelet reactivity (HRPR) in patients undergoing drug-eluting coronary stent implantation.

Methods: In a randomized, open-label, single-center, prospective study, the degree of platelet inhibition by cilostazol 100 mg twice daily was assessed on top of conventional DAPT compared with standard clopidogrel and low-dose aspirin combination in poststent patients with HRPR.

Impact of Bleeding on Myocardial Infarction, Stroke, and Death During 12 Months Dual Antiplatelet Therapy After Acute Coronary Syndrome.

Background: Bleeding remains a complication during dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). Some data suggest a link between bleeding and worsened vascular outcomes. However, this association is unclear, due to omitting of minor bleedings when applying conservative scales.

Effect of Sulodexide on Circulating Blood Cells in Patients with Mild COVID-19.

Background. Despite the fact that COVID-19 usually manifests with severe pneumonia, there is a growing body of evidence that life-threatening multiorgan damage is caused by vascular and hemostatic abnormalities. Since there is no established therapy, assessing antithrombotics is indeed important.

Primary Causes of Death Reported to the FDA Suggest Less Ticagrelor Mortality Benefit than the List Issued to the PLATO Trial Investigators.

Background: The PLATO trial data set reported to the FDA (DRFDA) revealed that some primary deaths causes (PDC) were inaccurately reported favoring ticagrelor. Trial Investigators (DRTI) received different data set with more ticagrelor mortality advantage. We compared these two death lists for the match in PDC.

Enoxaparin dose impacts blood cell phenotypes during mild SARS-CoV-2 infection: the observational single-center study.

Coronavirus disease 2019 (COVID-19) is associated with various hemostatic abnormalities requiring constant search for better delicate antithrombotic management in these high-risk patients. The choice and the optimal dose of anticoagulant is important, but unclear, especially for mild COVID-19. Enoxaparin has been tested in several COVID trials with mixed results regarding hard clinical outcomes including mortality.

Infections Deaths in the PLATO Trial.

 Cardiovascular benefits of aggressive dual antiplatelet therapy may be associated with extra risks including bleeding, cancer, and infections discovered first for prasugrel in the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel (TRITON) trial. Ticagrelor in PLATO also caused slightly more infections but surprisingly less sepsis-related deaths (SRD) than clopidogrel. However, verified infection fatalities in PLATO were lacking from the public domain.

FDA PLATO deaths list challenges aspirin dose-ticagrelor interaction.

No abstract present.

Impact of olokizumab on platelets, leukocytes and erythrocytes during mild COVID-19.

No abstract present.

Mild COVID-19 and Impaired Blood Cell-Endothelial Crosstalk: Considering Long-Term Use of Antithrombotics?

Background: Current coronavirus disease 2019 (COVID-19) pandemic reveals thrombotic, vascular, and endothelial dysfunctions at peak disease. However, the duration, degree of damage, and appropriate long-term use of antithrombotic strategies are unclear. Most COVID data are yielded from random clinical observations or autopsy of postmortem samples, while precise blood cellular data in survivors are insufficient.

Misreported Cancer Deaths in PLATO Trial.

The potential link between antiplatelet agents and anticoagulants with excess cancer deaths (CD) was reported first for prasugrel (TRITON, DAPT), clopidogrel (DAPT), vorapaxar (TRACER), apixaban (APPRAISE-2), and later ticagrelor (PEGASUS). However, verified CD in the ticagrelor indication-seeking PLATO were not public. We obtained the complete list of deaths and their primary causes in PLATO, matched that dataset against local site records, and analyzed the patterns of CD reporting.

Impact of VKORC1, CYP2C9, and CYP4F2 Polymorphisms on Optimal Warfarin Dose: Does Ethnicity Matters?

Background: Conventional anticoagulation with warfarin remains the cornerstone strategy for numerous preventive strategies. It is established that Asian patients require lower warfarin doses than Caucasians potentially attributing to the genetic polymorphism (GP) differences.

Areas Of Uncertainty: The impact of GP on optimal warfarin dose (OWD) in Koreans is unclear when compared with other ethnicities.

The FDA and PLATO Investigators death lists: Call for a match.

Purpose: The FDA-issued PLATO trial dataset revealed that some primary death causes (PDCs) were inaccurately reported favouring ticagrelor. However, the PLATO Investigators operated the shorter death list of uncertain quality. We compared if PDC match when trial fatalities were reported to the FDA and by the PLATO Investigators.

Verifying Death Reports in the Platelet Inhibition and Patient Outcomes (PLATO) Trial.

Background: Excess vascular deaths in the PLATO trial comparing ticagrelor to clopidogrel have been repeatedly challenged by the Food and Drug Administration (FDA) reviewers and academia. Based on the Freedom of Information Act, BuzzFeed won a court order and shared with us the complete list of reported deaths for the ticagrelor FDA New Drug Application (NDA) 22-433. This dataset was matched against local patient-level records from PLATO sites monitored by the sponsor.

Cost-effectiveness of Platelet Function-Guided Strategy with Clopidogrel or Ticagrelor.

Unlabelled: Some patients treated with dual antiplatelet therapy (DAPT) following acute coronary syndrome (ACS) can still exhibit heightened residual platelet reactivity (HRPR), which is potentially linked to adverse vascular outcomes. Better tailored DAPT strategies are needed to address this medical need.

Aim: To assess the cost-effectiveness of guided DAPT with clopidogrel or ticagrelor in addition to aspirin when using VerifyNow P2Y testing in post-ACS patients.

Does Ivabradine Decrease Cardiovascular Deaths in Heart Failure Patients?

Background: Ivabradine, a heart rate-slowing drug used to treat heart failure and (in Europe) angina, had varying impacts upon cardiovascular events in its 3 large outcome trials. Food and Drug Administration (FDA) analyses may explain the reasons for the variability.

Methods: An FDA reviewer analyzed the raw data from the 3 trials using logistic regressions to assess interactions between ivabradine and other drugs and forest plots to display dose responses.

Erratum to: "Comparison of ACUITY, CRUSADE, and GRACE Risk Scales for Predicting Clinical Outcomes in Patients Treated with Dual-Antiplatelet Therapy".

[This corrects the article DOI: 10.1055/s-0038-1675576.].