High "on Treatment" Platelet Reactivity in the Intensive Care Unit

High "on treatment" platelet reactivity is defined as a poor pharmacodynamic response to the administration of acetylsalicylic acid or clopidogrel. acetylsalicylic acid and clopidogrel are drugs commonly used to reduce platelet activity and prevent cardiovascular events. High "on treatment" platelet reactivity is associated with a higher cardiovascular event rate. Ticagrelor and prasugrel, like clopidogrel both P2Y12 inhibitors are effective in treating patients with High "on treatment" platelet reactivity to clopidogrel. Critically ill patients are a unique population with altered pharmacokinetic and pharmacodynamic properties. Gastrointestinal dysmotility with associated altered resorption and impaired microvascular function occur frequently in critically ill patients and may lead to altered resorption of orally administered drugs. The investigators will test a minimum of 100 patients treated with 100mg acetylsalicylic acid per os and 100 patients treated with 75mg clopidogrel per os to calculate the prevalence of high "on treatment" platelet reactivity. 30 patients with high "on treatment" platelet reactivity to acetylsalicylic acid will be randomized to three new treatment groups. In the first group patients will receive 200mg acetylsalicylic acid per os, in the second group 100mg acetylsalicylic acid intravenously and in the third group 81mg chewable acetylsalicylic acid. Each group will contain 10 patients. Pharmacokinetics and pharmacodynamics will be reassessed to evaluate the new treatment. 36 patients with high "on treatment" platelet reactivity to clopidogrel will be randomized to receive either an additional loading dose of 600mg clopidogrel (n=24) or to continue normal treatment as a control group (n=12). Pharmacokinetics and pharmacodynamics will be reassessed and those patients, who are tested again to have high "on treatment" platelet reactivity in spite of the additional loading dose, will now be randomized to receive either ticagrelor or prasu