International Circulation: The SATURN trial was presented at this meeting. In clinical practice， physicians tend to not use high dose statins due to concerns about safety issue. The SATURN trial though has shown that the highest doses of two potent statins achieved unprecedented atherosclerotic plaque regression and were well tolerated. Do you think these results will encourage physicians to use statins in a more aggressive way?
　　国际循环（IC）：SATURN试验结果已经公布。在临床实践中，临床医生常由于担心安全性问题而不愿使用高剂量他汀。SATURN试验结果显示2种最高剂量使动脉粥样硬化斑块逆转达到前所未有的高比例，且耐受性良好。您认为这一结果是否会促使临床医生以更积极的方式去实施他汀治疗？
　　Prof Ballantyne: I think the results should encourage physicians to use statins aggressively. I also think that in an Asian population， one can be driven by the LDL and non-HDL targets. If a patient is more sensitive， and we see this sometimes in Chinese/Japanese populations， a 10mg dose can achieve the same LDL levels as a 20mg dose in a Western/US patient. I might extrapolate these data to say that a 20mg dose of rosuvastatin is one that allows you to achieve very low levels of LDL and approaching the targets where we will see regression and this is the effect that would be seen with 40mg rosuvastatin.
　　Prof Ballantyne: 我认为这一结果会鼓励临床医生更积极地进行他汀治疗。我还认为在亚洲人群中，可以采用LDL-C和非HDL-C靶标指导治疗。有可能亚洲患者对药物更敏感，我们观察到在中国和日本人群中，10mg剂量可能达到和欧美人群中应用20 mg剂量同样的LDL-C水平。据此推断，瑞舒伐他汀20 mg可能达到非常低的LDL-C水平并实现斑块逆转，正如试验中欧美人群40 mg瑞舒伐他汀逆转斑块的结果。
　　Prof Yan: Actually in China we try to lower the LDLc aggressively in patients with acute coronary syndrome and coronary artery disease plus diabetes with a target of 80mg/dl in these patients. The percentage of patients that reach this target level is very small. After the SATURN trial， we have learned that aggressive treatment to a low LDL level is helpful in the regression in atheroma. I think the trial is important for Chinese doctors in getting them to take an aggressive approach to lowering LDLc. I totally agree with Professor Ballantyne; it is not a problem of dose， it is a problem of whether we can achieve a substantial reduction of LDLc.
　　严晓伟教授：的确，在中国我们对ACS和冠心病合并糖尿病患者要求将LDL-C降至80 mg/dl以下，但达标率非常低。通过SATURN试验，我们认识到强化他汀治疗以降低LDL-C对逆转斑块非常有帮助。这一结果对促使中国医生更积极地降低LDL-C有重要意义。我完全赞同Ballantyne教授的观点，这不是剂量的问题，而是我们能否确保LDL-C达标的问题。
　　International Circulation: The ESC/EAS Joint Guidelines were also amended to recommend very low LDLc levels especially in high risk patients; that recommendation was for 70mg/dl for patients at very high risk or at least a 50% reduction if that goal in unachievable. There are a lot of statin agents， but not all statins are potent enough to achieve such results. In our daily practice， how do doctors choose a statin to achieve these goals?
　　IC：ESC/EAS血脂异常管理指南对LDL-C治疗目标值做出了更严格的要求，尤其对极高危患者，要求将LDL-C降至70 mg/dl以下或至少降低50%。但实际上并非所有他汀均能达到这一要求。在临床实践中，医生应如何选择他汀以促使LDL-C达标？
　　Prof Ballantyne: The usual steps would be to ask， what is the risk status of the patient? You mentioned there are high risk patients (ACS， coronary disease with diabetes) and for me (and I am a little more simplistic sometimes)， if the patient has documented coronary atherosclerosis or had any type of event， that type of patient merits a very intensive strategy. The ACC Guidelines say to target <100mg/dl， but it is reasonable to get to <70 if you can， or a 50% reduction as stated in the ESC Guidelines. I think that is very reasonable. There are going to be patients who are lower risk (primary prevention， they may only have one risk factor or according to the various risk scores) and here we can have less aggressive targets. The first thing is to determine what the risk of your patient is and then establish a goal. The next issue is to select a statin which can achieve that goal. To get <70 or <80 requires very effective therapy approaching a 50% reduction.
　　Prof Ballantyne: 首先应明确患者的危险分层。你提到了极高危患者（ACS、冠心病合并糖尿病），对我而言（我有时将问题尽量简化），如果一位患者明确存在冠状动脉粥样硬化或发生过任何事件，就应该给予强化治疗策略。ACC指南要求目标值为LDL-C<100 mg/dl，但如果我们能够做到，那么达到<70 mg/dl或如ESC指南的要求至少降低50%无疑是更合理的。还有一些较低危的患者（一级预防，有可能仅有1项危险因素或根据不同的风险积分），可以设定稍微保守的目标值。所以首先要确定患者的危险分层，然后设定目标值。其次是选择能够使患者达标的他汀药物，将LDL-C降至<70或80 mg/dl或降低50%，都要求非常有效的疗法。
　　International Circulation: What is the situation in China? We know that statin usage rates are very low in China， as low as 1.7% of patients who should be using statins.
　　IC：中国的现状如何？据了解中国他汀治疗率非常低，在应使用他汀的患者中他汀治疗率仅达到1.7%？
　　Prof Yan: The most commonly used statins in China is simvastatin and atorvastatin because rosuvastatin has only just come onto the market recently. In terms of atorvastatin， it is safer to use at a higher dose and the effect on LDLc is also larger than that of simvastatin. Now we have rosuvastatin. I think in the future we will see more relatively higher dose rosuvastatin being employed to lower LDLc.
　　严晓伟教授：中国最常使用的是辛伐他汀和阿托伐他汀，瑞舒伐他汀在中国上市较晚。与辛伐他汀相比，阿托伐他汀高剂量的安全性和降低LDL-C的效果更好。现在我们拥有了瑞舒伐他汀，我认为未来我们会更多地使用较高剂量的瑞舒伐他汀以更有效地降低LDL-C。
　　Prof Ballantyne: That is what we have seen in the United States. You have the high efficacy statins， rosuvastatin and atorvastatin and there are the lower efficacy statins， pravastatin and lovastatin and the midrange simvastatin. As you pointed out， when you go to the high dose simvastatin， you get more muscle side effects and more drug interactions as reported both in the United States and more recently in China in a large clinical trial with niacin and simvastatin drug interactions. It is one we need to be cautious with. We need to be cautious because the patients we are talking about (coronary disease with diabetes， hypertension) are on multiple medications so the chances of drug interactions are highest on simvastatin.
　　Prof Ballantyne: 我们在美国看到的情况有些相似。我们拥有强效他汀如瑞舒伐他汀和阿托伐他汀，还有一些降脂效应稍弱的他汀，包括普伐他汀、洛伐他汀和中剂量辛伐他汀。如你所说，高剂量辛伐他汀会导致更多的肌肉不良反应，此外，近期在中国和美国进行的一项大型临床试验显示辛伐他汀和烟酸之间存在较多的药物相互作用，这是必须予以重视的，因为我们讨论的患者（冠心病合并糖尿病、高血压）通常同时服用多种药物，高剂量辛伐他汀发生药物间相互作用的几率是最高的。
　　International Circulation: We know most statins are metabolized by CYP450 but several statins do not go through that pathway， such as rosuvastatin and pravastatin. Is this a point of consideration when choosing a statin?
　　IC：多数他汀是经肝脏CYP450代谢，而有些他汀的代谢途径不同，如瑞舒伐他汀、普伐他汀。选择他汀时是否应考虑这些因素？
　　Prof Ballantyne: It is another consideration: high risk patient， needs aggressive LDL targets and is more likely to be on multiple drugs， so it certainly needs to be part of the thought process.
　　Prof Ballantyne: 应该考虑，高危患者通常需要将LDL-C降得更低，同时也更可能在服用多种药物，因此必须考虑这些因素。
　　International Circulation: We know from the 2007 JAMA meta-analysis， only when a  statin can significantly lower the LDLc level and increase HDLc level at the same time can it achieve substantial plaque regression. The SATURN trial showed rosuvastatin can raise HDL by almost 10% which is significantly greater than atorvastatin. Also in patients achieving higher HDLc levels， the rosuvastatin group showed more significant improvement in plaque regression than atorvastatin. Professor Ballantyne， what is your take on this aspect of the results?
　　IC：2007年发表于JAMA的一篇荟萃分析提示，只有当一种他汀显著降低LDL-C同时大幅升高HDL-C，才能真正实现斑块逆转。SATURN试验显示瑞舒伐他汀升高HDL-C近10%，显著高于阿托伐他汀；同时在HDL-C水平更高的患者中，瑞舒伐他汀逆转斑块的效益比阿托伐他汀更显著。您如何评价这些结果？
　　Prof Ballantyne: The hypothesis of the study was that lipoproteins are one of the main drivers of atherosclerosis. The trial was designed because rosuvastatin gives a little more reduction in LDL and ApoB and also greater increases in HDLc and ApoA1. What we saw in the study was that the difference in LDLc reduction was about 63mg/dl versus 70mg/dl; there was a greater increase in HDLc， 48.6 versus 50.4; and the ratio of LDL to HDL was better. The results were pretty close to what we thought; we thought maybe there would be a slightly bigger difference. The results were consistent with the hypothesis. The primary endpoint was that both show regression on the percent atheroma volume but there was not a significant difference. There was a trend towards greater benefit with the rosuvastatin group. On the secondary endpoint， they both showed a reduction in the total atheroma volume but the reduction was significantly greater in the rosuvastatin group. All-in-all， if we plot out the results on the LDLs achieved， these results are consistent with the hypothesis that lipoproteins and specifically atherogenic lipoproteins (LDL， ApoB apolipoproteins) lead to the regression of atherosclerosis if we can lower levels dramatically and also that raising HDLc is beneficial. That is supportive of the hypothesis that we had when we embarked on the trial.
　　Prof Ballantyne: 本试验的假设是，脂蛋白是动脉粥样硬化的主要驱动因素之一。设计本试验是由于瑞舒伐他汀降低LDL-C及ApoB和升高HDL-C及ApoA1的效果更强。研究结果显示，与阿托伐他汀组相比，瑞舒伐他汀组治疗后LDL-C水平更低（63mg/dl vs 70mg/dl），HDL-C水平更高：48.6 vs. 50.4；LDL-C /HDL-C比率更佳。这些结果接近我们的预期，也与假设相一致。主要终点显示2组均逆转了PAV但无统计学差异，但瑞舒伐他汀呈获益更大的趋势。次要终点上，2组均降低了TAV，但瑞舒伐他汀组TAV降低幅度显著更大。总之，以治疗后达到的LDL-C水平而言，试验结果与假设是一致的，即，如果我们能够大幅降低致动脉粥样硬化脂蛋白（LDL、ApoB）就可能逆转动脉粥样硬化斑块，同时升高HDL-C当然也是有益的。
　　Prof Yan: In terms of LDLc there is no problem. There is benefit in reducing LDL for the patient and for the atheroma. For HDLc it is very difficult to say. In epidemiological studies there is a reverse correlation between HDLc and cardiovascular events but after drug intervention， what the implication is of a change in HDLc is hard to say.
　　严晓伟教授：降低LDL-C对患者和斑块都是有益的。HDL-C的问题还需要探索。流行病学研究显示HDL-C水平和心血管事件间呈负相关，但药物干预后HDL-C水平的变化有何意义还不明确。
　　Prof Ballantyne: I would agree with that. That is why our guidelines remain focused on lowering LDLc， non-HDLc and ApoB， and as a secondary consideration， was there a favorable effect on HDL or ApoA1? The major focus remains on reducing the ‘bad’ cholesterol.
　　Prof Ballantyne:同意严教授的观点。这也是指南仍然聚焦于降低LDL-C、将非HDL-C和ApoB作为次要靶点的原因。升高HDL-C和ApoA1有无获益尚不明确。主要问题仍然是降低“坏”胆固醇。
　　International Circulation: The SATURN trial showed that rosuvastatin can reduce ApoB and non-HDLc components more than atorvastatin. Is that why rosuvastatin performs better with the secondary endpoint of the study?
　　IC：SATURN试验结果显示瑞舒伐他汀降低ApoB 和 non-HDL-C的作用优于阿托伐他汀。这是瑞舒伐他汀降低TAV优于阿托伐他汀的原因之一吗？
　　Prof Ballantyne: We knew from the other lipid studies done prior to this， that we would see more reduction in LDL， ApoB and non-HDL. There are two endpoints， percent atheroma volume (PAV) and total atheroma volume (TAV). If we go back to the initial trials the order had been reversed. The primary endpoint has been total atheroma volume and the secondary had been percent atheroma volume. When you are comparing two statins that are both effective and only for two years， we knew that the difference was not going to be enormous， so we chose the endpoint which would have the smallest inner deviations. One could make the argument that total atheroma volume makes the most sense in a biological sense in terms of regression of atherosclerosis. But the primary endpoint was trending in the right direction; the secondary endpoint was significant. I think you are correct， that the differences in LDL， ApoB and non-HDL were the reasons why we saw the benefits.
　　Prof Ballantyne: SATURN试验有2项终点，PAV和TAV。既往研究中其顺序是相反的，主要终点多为TAV而次要终点多为PAV。当我们试图在短短2年中比较2种强效他汀时，我们知道组间差异不会太大，因此选择了内部偏差最小的终点。有人可能会认为，就动脉粥样硬化逆转而言，TAV是最敏感的生物学指标。但是主要终点反映了正确的趋势，而次要终点达到统计学差异。我认为你的观点是对的，2组间LDL-C、ApoB和non-HDL-C的降低是瑞舒伐他汀组更多获益的原因。