International Circulation: In oral anticoagulant therapy， how can we make the balance between safety and efficacy?

《国际循环》：关于口服抗凝药治疗，我们如何保持安全性和有效性之间的平衡？

Prof. Dan: It is not very easy especially with the medication we have now. In my opinion these medications should be changed in the future to be safer and much easier to control therapy. But for the moment， the tool we have to control such therapy which has a good balance between efficacy and safety is to look after the INR – to have an INR which is strictly in the range of 2 to 4， not below 2 and not above 4. This has been demonstrated by many papers to be inside the therapeutic range and outside the hemorrhagic range.

Dan教授: 我们使用的药物做到这一点并不太容易。今后随着药物的改进，治疗监测会更安全更容易。目前我们监测治疗，以便保持有效性和安全性的平衡是通过监测INR，严格控制INR在2~4范围之间，既不要低于2也不要高于4。诸多研究显示，INR2~4为有效药物治疗范围，超过4是出血的范围。

International Circulation: For the patient with ACS and AF， they might accept aspirin， clopidogrel and warfarin， which are related to fatal bleeding. What is your opinion about this?

《国际循环》：对于急性冠脉综合症（ACS）合并房颤（AF）的患者，可能需要接受阿司匹林、氯吡格雷以及华法林治疗，这可能会导致致死性的出血情况。关于这个问题您有何意见？

Prof. Dan:  The patient with atrial fibrillation and coronary artery disease is a very special patient and it is not a rare patient. The risk of atrial fibrillation increases with ischemic heart disease and increases with age. Both fibrillation and coronary disease increase with age so we have a lot of patients with this combination. As demonstrated， the combination of aspirin， clopidogrel and oral anticoagulants increase three to five-fold the hemorrhagic risk.  We should be very careful in indicating triple therapy in such patients. We need to select very closely those patients suited to this triple indication and these patients who may benefit from triple therapy are the patients with very difficult lesions on the coronary tree， with a high risk of restenosis， and who deserve drug-eluting stents. I emphasize that nobody should utilize drug-eluting stents in patients with atrial fibrillation as a routine.  In patients with atrial fibrillation on oral anticoagulants， the routine indication should be bare metal stents because bare metal stents implies double therapy not triple therapy. In some patients it is impossible so we should have triple therapy but shorten the triple therapy as much as possible， at least to one month then put the patient on double therapy.

Dan教授: 合并有心房颤动（房颤）的冠状动脉病变的患者是比较特殊的，但并不少见。缺血性心脏病患者房颤的风险增高，其风险也随着年龄增加而增加。房颤和冠心病的发病率都随着年龄增加而增加，因此有很多患者合并有这两种疾病。联合使用阿司匹林、氯吡格雷和口服抗凝药使出血的风险增加3~5倍。因此此类患者选择三种药物治疗必须非常小心，必须严格筛选。对于冠状动脉血管病变复杂、再狭窄率高、植入药物洗脱支架的患者可能从三联抗血栓治疗中获益。在这里我需要强调的是，房颤患者不能常规使用药物洗脱支架。房颤患者需要口服抗凝药，常规应使用裸金属支架，因为裸金属支架只需双重抗栓治疗，不需要三重抗栓治疗。部分患者可能并不能做到这一点，导致我们需要三重抗血栓治疗，但也应尽可能缩短三药联合治疗时间，最多使用1月后换成双重治疗。

International Circulation: Aspirin and clopidogrel resistance are emerging clinical entities with potentially severe consequences such as recurrent myocardial infarction， stroke， or death. Is double-dose or triple anti-platelet therapy a good idea? What is your opinion?

《国际循环》：在临床上出现的阿司匹林和氯吡格雷抵抗现象有潜在的严重后果，例如再发心梗、卒中、甚至死亡。此时剂量加倍或使用三种抗血小板药物 是否合适？您有何意见？

Prof. Dan: Unfortunately， I am not sure we can surpass the resistance only by using double or triple therapy. The demonstration of resistance implies a very special tool which is not clinically available yet available clinically to individualize patients really resistant to therapy. There are two kinds of patients: the real resistant and we should be able to see the patients that are really resistant to anti-platelet therapy; and the pseudo-resistant， who are patients who are not taking the medication so are not really resistant. But the resistant group is a real problem. In my opinion， it is not with triple therapy that we can solve this problem but with alternative antiplatelet agents. The best known problem is the patient who is resistant to aspirin. In these patients probably the administration of clopidogrel long-term， as we are talking about the coronary patients， is one alternative. In several patients with resistance to aspirin and clopidogrel， and fortunately there are not many patients resistant to both because they have different genetic mechanisms， oral anticoagulants could be a solution but oral anticoagulants are much less effective than anti-platelet agents in these indications. The solution for the resistant patients for the moment could be a powerful association but keeping in mind the risk of hemorrhage and for the future the solution should be an alternative anti-platelet agent. There are many on the pipeline， already tested in randomized controlled trials in phase III and maybe will be an alternative to change from clopidogrel to dabigatran or some new agents. The main problem for the moment is to identify and individualize the patients who are resistant.

Dan教授:  很遗憾，我不能肯定上述做法可以克服药物抵抗这个问题。药物抵抗暗示着需要特殊的解决方法，目前临床上针对患者个体化治疗药物抵抗的问题还无法解决。临床上有两类患者：一类是真正的抵抗，这类患者对于抗血小板治疗无效；另一类是假性抵抗，此类患者不服药因此不算是抵抗。但抵抗的分类的确是个问题。我觉得，三重治疗并不能解决问题，而应该选择其他可选择的抗血小板药物。最熟悉的阿司匹林抵抗问题，此类冠脉病变的患者可以选择长期使用氯吡格雷。有部分患者既对阿司匹林抵抗，又对氯吡格雷抵抗，好在这类患者并不多，因为这两种药对血小板抑制的作用机制不同，此类患者可以使用口服抗凝药，但是口服抗凝药与抗血小板药物相比的效果差一些。目前也有联合多种药物使用来解决抵抗的问题，但是必须警惕出血的发生。今后，可以通过选择其他抗血小板药物来解决抵抗的问题。新型的抗血小板药物有很多种，而且已经进入III期随机对照研究，今后可能使用达比加群酯或其他新的药物替代氯吡格雷。目前的主要问题是区别哪些是血小板抵抗的患者。

International Circulation: For the patients with chronic renal function failure， is there any difference from other patients with ACS in the management of antiplatelet therapy?

《国际循环》：慢性肾功能不全的患者抗血小板治疗的实施方法与ACS患者有何差别？

Prof. Dan: Undoubtedly there is a difference. We need to keep in mind two things. First， renal patients have a high cardiovascular mortality， so they should be treated carefully for the cardiovascular mortality and they are indicated for anti-platelet therapy. There should be monitoring of the dosage particularly with some anti-thrombotic agents， for example， enoxaparin. The new guidelines are very clear on adapting the dose of enoxaparin in patients with renal failure – no loading dose， lower dose per kilogram bodyweight. Secondly， with anti-platelet therapy， especially aspirin and clopidogrel， monitoring should be conducted very closely. Fortunately for us， the efficacious aspirin dose is very low， so in the majority of patients with renal disease it is not toxic and clopidogrel has not demonstrated interference with renal disease.

Dan教授:两者之间的确存在差别。有两点我们需要牢记。首先，肾病患者心血管疾<