Development of a Novel Oral Anticoagulant with Minimal Bleeding Risk

在静脉或动脉中产生血块是一种非常严重的疾病，仅在英国每年就导致22.5万人死亡。抗凝剂是用来预防或治疗血栓的。心律异常（心房颤动）的患者发生脑血栓（中风）的可能性是正常患者的5倍。华法林是一种抗凝血药物，可以将中风的高风险降低64%。然而，华法林是一种难以管理的药物，因为它需要每个月进行血液样本监测，以确保体内药物的正确水平。此外，华法林有导致大出血的风险，每100名服用该药的患者中就有3人出血，其中每8人中就有1人死亡。最近，一种新药达比加群被批准长期用于治疗房颤患者。这种新药的好处是患者不再需要血液样本监测。然而，所有现有的抗凝药物和正在开发的新抗凝药物都存在一个问题，那就是它们仍然有很高的出血风险。在这项建议中，我们正在首次开发一种新的抗凝血药物，它不需要监测，使用时不太可能导致出血。如果我们取得成功，这有可能改变抗凝治疗，提高患者的生活质量，并通过不必治疗出血并发症而大大节省患者的医疗保健费用。

The generation of a blood clot in a vein or artery is a very serious condition, ultimately causing 225,000 deaths per year in the UK alone. Anticoagulants are prescribed to prevent or treat blood clots. Patients that have an abnormal heart rhythm [atrial fibrillation (AF)] are 5 times more likely to have a blood clot in the brain (stroke). Warfarin, an anticoagulant drug, can reduce this high risk of stroke by 64%. However, warfarin is a difficult drug to administer as it needs to be monitored with a blood sample every month to ensure the correct level of drug is in the body. Furthermore, warfarin carries a risk of causing major bleeding for up to 3 in 100 patients taking the drug of which 1 in 8 will die. Recently a new drug, dabigatran has been approved for long term use to treat patients with AF. The benefit of this new drug is that patients no longer need to be monitored with a blood sample. However, one problem that all existing anticoagulant drugs and the new ones that are being developed have is that they still carry a very high risk of bleeding. In this proposal, we are developing for the first time a new anticoagulant drug that will not need monitoring and is not likely to result in bleeding when used. If we are successful, this has the potential to transform anticoagulation treatment, improve patient quality of life and make large savings to the cost of patient healthcare through not having to treat bleeding complications.