Thrombin receptor antagonists as prophylaxis to complications from cardiopulmonary surgery

Abstract

Disclosed herein are methods of preventing, inhibiting, or ameliorating complications associated with cardiopulmonary bypass surgery by the use of a thrombin receptor antagonist compound. Among the thrombin receptor antagonis compounds useful in these methods are those of Formulas (I), (II) and (III), described herein. Examples of such thrombin receptor antagonists include formulae (I), (II) and (III).

Description

Background technique [0001] Approximately 709,000 cardiopulmonary bypass operations ("CPB") are performed each year in the United States, making it the most frequently performed major operation. Surgeries that use CPB include coronary artery bypass graft surgery ("CABG"), cardiovascular repair and repositioning surgery, and pericardial and aortic repair surgery. Any procedure that includes CPB surgery can include a series of common hazards largely associated with the contact of circulating blood with the surface of the shunt device. This contact can lead to clot formation, which can pose a serious risk of stroke to the patient. CABG surgery can pose other risks to patients. [0002] CABG surgery is recommended for selected patient groups with significant stenosis and obstruction of the heart arteries (coronary artery disease). CABG surgery creates new pathways around narrowed and blocked arteries, allowing sufficient blood flow to deliver oxygen and nutrients to the heart muscle. ...

AI Technical Summary

Problems solved by technology

Bleeding is inevitable during this procedure, and platelet activation (and thus loss) is significantly exacerbated by the use of externalized circulation and pumps

Bleeding risk is further increased by administration of clopidogrel, so many surgeons will delay CABG for five to seven days to allow washout of previous clopidogrel (according to US surgical guidelines and US labeling)

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