Loss of Effect of Aspirin on Platelet Aggregation During Chronic Administration

Loss of Effect of Aspirin on Platelet Aggregation During Chronic Administration

Aspirin has shown to be beneficial to some patients with certain diseases such as coronary artery disease or stroke. We are investigating how aspirin works on regulating platelets and thromboxane over time at different doses. We hope to find the best dose of aspirin and/or other medications to help people who are at risk for heart attack or stroke.

he purpose of the study is to better understand the mechanism for failure of daily aspirin administration to prevent cardiovascular events in some at risk individuals. We seek to describe the effect of chronic aspirin administration at varying doses on platelet aggregation. This will help to define mechanisms for aspirin failure and to pursue possible alternative therapies in patients who fail to respond to aspirin therapy.

We hypothesize that (1) inhibition by aspirin (ASA) of ex vivo-induced platelet aggregation varies in a predictable time and dose dependent manner, (2) thromboxane and prostacyclin production is inhibited by ASA in a dose-dependent manner and remains relatively constant over time once maximal inhibition has occurred, and (3) granule secretion by platelets during induced aggregation is inhibited by aspirin acutely but this effect does not persist during chronic administration at high doses.

Inclusion Criteria:

• Males
• Age 18-40 years
• Non-smokers

Exclusion Criteria:

• ASA/NSAID use previous 14 days.
• Evidence of ASA/NSAID use within previous 14 days at baseline visit based on investigator interpretation of platelet aggregation and platelet secretion studies.
• History of chronic NSAID use.
• Currently taking NSAIDs, corticosteroids, or anticoagulants.
• History of coronary artery disease, myocardial infarction, coronary artery bypass grafting, percutaneous angioplasty, diabetes mellitus or stroke.
• History of gastric,duodenal, or esophageal ulcers or serious gastrointestinal bleed.
• History of frequent headaches, pain syndrome, or other condition requiring frequent use of analgesics.
• History of adverse reaction to ASA.
• Initial platelet count <100K/µl or >500K/µl.
• Initial hematocrit <35% or >50%.
• Weight less than 110 pounds.