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.

Pharmacokinetics and pharmacodynamics of the antiplatelet combination aspirin (acetylsalicylic acid) plus extended-release dipyridamole are not altered by coadministration with the potent CYP2C19 inhibitor omeprazole.

Background: The fixed-dose combination of aspirin (acetylsalicylic acid) 25 mg plus extended-release dipyridamole 200 mg (ASA+ER-DP) is used for long-term secondary stroke prevention in patients who have experienced non-cardioembolic stroke or transient ischemic attack. Although the theoretical risk is low that the antiplatelet activity of ASA+ER-DP will be affected by concomitant use of a proton pump inhibitor (PPI), no formal drug-drug interaction studies have been conducted.

Objective: This study aimed to determine whether the PPI omeprazole influences the pharmacokinetic (PK) and pharmacodynamic (PD) behavior of ASA+ER-DP.

Monocyte chemotactic protein-1 as a potential biomarker for early anti-thrombotic therapy after ischemic stroke.

Inflammation following ischemic brain injury is correlated with adverse outcome. Preclinical studies indicate that treatment with acetylsalicylic acid + extended-release dipyridamole (ASA + ER-DP) has anti-inflammatory and thereby neuroprotective effects by inhibition of monocyte chemotactic protein-1 (MCP-1) expression. We hypothesized that early treatment with ASA + ER-DP will reduce levels of MCP-1 also in patients with ischemic stroke.

Dipyridamole in antithrombotic treatment.

The antithrombotic activity of dipyridamole was initially discovered in an in vivo experiment about half a century ago. At that time science had not appreciated the complexity of the regulation of local thrombus formation. Inhibition of platelets has been the main focus for the prevention of arterial thrombus formation.