Scardi Sabino, Giansante Carlo
Centro Cardiovascolare, Azienda Sanitaria Triestina, Trieste.
Ital Heart J Suppl. 2004 Sep;5(9):705-11.
Non-rheumatic atrial fibrillation (NRAF) is one among the major public health problems, because it is associated with a high incidence of stroke or systemic thromboembolism. Warfarin significantly reduces cerebral/systemic events mainly in high-risk patients; unfortunately such drug is often as well under-used in eligible patients as under-dosed in treated patients. Traditional therapy with oral anticoagulants has several disadvatages: narrow therapeutic window, and often unpredictable dose-response so that frequent monitoring of the INR is required. It is therefore crucial that patients preferences and education be integrated into the decision-making process. Physicians often underprescribe oral anticoagulants since they perceive the risk of major bleeding as unacceptable because of some well known risk factors (e.g. previous bleedings, severe hypertension), and of qualms about drug interactions or alleged poor compliance. Therefore, the development of easy-to-use antithrombotic agents is still a challenge. New agents such as oral direct thrombin inhibitors are going to hold the promise for the next future. Ximelagatran is an orally active small molecule; being the first new oral anticoagulant used in large clinical trials. This molecule has many advantages in comparison to warfarin, such as the rapid onset/offset of action, the fixed oral dose, the no need of dose adjustment or of anticoagulation monitoring, as well the lack of food/alcohol intake interference as of drug interactions. The SPORTIF III and V trials have shown that ximelagatran is not inferior to warfarin in the prevention of strokes in patients with NRAF (both persistent and paroxysmal), but a side effect--consisting in the significant elevation of liver enzymes (> 3 times the upper limit of normal) in 6% of patients--was found. Further randomized trials are clearly needed, while current data suggest that ximelagatran will be able to represent a future viable therapeutic option for prevention of thromboembolism in patients with NRAF, offering huge advantages with respect to classic oral anticoagulants.
非风湿性心房颤动（NRAF）是主要的公共卫生问题之一，因为它与中风或全身性血栓栓塞的高发病率相关。华法林主要在高危患者中显著降低脑/全身性事件的发生率；不幸的是，这种药物在符合条件的患者中经常使用不足，在接受治疗的患者中剂量也经常不足。传统的口服抗凝剂治疗有几个缺点：治疗窗窄，剂量反应往往不可预测，因此需要频繁监测国际标准化比值（INR）。因此，将患者的偏好和教育纳入决策过程至关重要。医生常常减少口服抗凝剂的处方，因为他们认为由于一些众所周知的风险因素（如既往出血、重度高血压）导致的大出血风险不可接受，并且对药物相互作用或所谓的依从性差感到担忧。因此，开发易于使用的抗血栓药物仍然是一个挑战。新型药物如口服直接凝血酶抑制剂有望在未来发挥作用。希美加群是一种口服活性小分子；是首个用于大型临床试验的新型口服抗凝剂。与华法林相比，这种分子有许多优点，如起效/失效迅速、口服剂量固定、无需调整剂量或进行抗凝监测，以及不存在食物/酒精摄入干扰和药物相互作用。SPORTIF III和V试验表明，在预防NRAF（持续性和阵发性）患者中风方面，希美加群并不逊于华法林，但发现有副作用——6%的患者肝酶显著升高（>正常上限的3倍）。显然还需要进一步的随机试验，而目前的数据表明，希美加群将能够成为未来预防NRAF患者血栓栓塞的可行治疗选择，与传统口服抗凝剂相比具有巨大优势。
