International Circulation: The SATURN trial looks at intensive statin therapy and its action on atherosclerotic plaque regression. Although this trial is not focusing on clinical outcomes， from your presentation we can see that major cardiovascular events in both drug groups were very low， about 7% in patients with established CAD. Do you think， from this and previous studies， that plaque regression can be translated into cardiovascular outcomes?
　　《国际循环》：SATURN观察了强化他汀治疗对动脉粥样硬化斑块逆转的作用。虽然这项试验并未重点观察临床结果，但是从您的报告中我们看到2组患者的主要心血管事件发生率均非常低，这组已明确诊断为冠心病的人群心血管事件发生率仅7%。从既往研究和SATURN试验结果看，您认为斑块逆转可以解读为临床结局的改善吗？
　　Prof Nicholls: We think so. We have looked at the relationship between plaque and outcome for many years， even before IVUS. It was quite clear that the more plaque you had， the more likely it was that you would have an event. And the more that plaque progresses over time， the more likely you would have an event as well. We saw that in our own data with IVUS in the last few years. I think what we have seen in this study is very reassuring for doctors and patients and that is if we use the highest doses of statin therapy， they are very safe and they are very well tolerated， they have very good effects on lipid levels leading to very low levels of LDL and actually very good levels of HDL and they actually also regress plaque. That was very much associated with a low event rate in those patients. So all together that is very encouraging for doctors who manage coronary disease.
　　Prof Nicholls: 我们认为是这样。即使在运用IVUS技术之前，我们已经对斑块和临床结果之间的关系观察了许多年。斑块越多，发生事件的可能性越高，这是非常明确的。而随着时间推移，斑块进展越明显，发生事件的可能性也越高。基于过去几年中我们自己进行的IVUS研究数据，我认为在SATURN试验中观察到的结果再次使医生和患者确信，使用最高剂量的他汀治疗非常安全，耐受性非常好，且对血脂水平由非常好的调节作用，达到非常低的LDL-C水平和很好的HDL-C水平，从而逆转斑块。这与患者非常低的事件发生率显著相关。总之，这一结果将大大增强医生管理冠心病的信心。
　　International Circulation: We know that the LDLc concentration has a positive linear correlation with disease progression. In the SATURN trial， both statins achieved very low levels of LDLc with rosuvastatin slightly better than atorvastatin. We also see that the reduction in total atheroma volume is significantly greater in the rosuvastatin group than the atorvastatin group. There is however no significant difference for the primary endpoint， PAV. What is your interpretation of that?
　　《国际循环》：我们知道LDL-C水平与疾病进展呈明显正线性关系。SATURN试验中，2种强效他汀均达到非常低的LDL-C水平，而瑞舒伐他汀组较阿托伐他汀组更低。同时瑞舒伐他汀组TAV的降低较阿托伐他汀组更显著。而PAV未达统计学差异。您如何理解这一结果？
　　Prof Nicholls: When we set out to do the SATURN study， the primary objective was to directly compare head-to-head the two statins， rosuvastatin and atorvastatin， and we have done that. What we observed is that there were some differences in lipid levels with rosuvastatin resulting in a slightly lower LDL and slightly higher HDL. We see that on the primary endpoint， both agents are very profound in terms of the regression; there is no difference between the two but there is a difference on the secondary endpoint. We know there are some differences between the two compounds and this is important information for doctors to use when trying to make choices for our patients in terms of how we manage patients with coronary disease. But overall， I think we have to be very satisfied that these are very effective agents. It is good to have choices.
　　Prof Nicholls:开展SATURN研究的主要目的是对瑞舒伐他汀和阿托伐他汀进行头对头比较。我们观察到2组血脂水平出现显著差异，瑞舒伐他汀治疗达到了更低的LDL-C和更高的HDL-C水平；对于主要终点，2种他汀均实现了斑块逆转而无显著差异，但次要终点显示了统计学差异。这些结果使我们认识到2种他汀间存在的差异，为医生治疗冠心病患者时选择用药提供了重要信息。2种药物均非常有效，我们对此感到满意，拥有多种选择是好事情。
　　International Circulation: You mentioned rosuvastatin achieved a slightly better HDL level than atorvastatin and also that in a subgroup， those with higher HDLc levels at baseline and those achieving higher HDLc levels than average responded better to rosuvastatin than atorvastatin with regard to PAV. What message does this give us?
　　《国际循环》：您提到瑞舒伐他汀治疗后达到了比阿托伐他汀组更好的HDL-C水平，并且在基线以及治疗后HDL-C水平更高的亚组中，瑞舒伐他汀组PAV的逆转也优于阿托伐他汀组。这一结果给我们什么样的启示？
　　Prof Nicholls: One always needs to be a little cautious in over-interpreting subgroups. We have been very cautious with that. We made a number of observations. It looked like patients who had high levels of HDL either at the start or the end of the study， tended to do better on rosuvastatin. Whether that reflects a difference in the functional activity of HDL (which is becoming very important in terms of our understanding the relationship between HDL and cardiovascular disease)， we don’t know. But it may reflect more functional HDL promoting more regression of disease but we obviously have a lot more work to do to try and understand these things more clearly.
　　Prof Nicholls: 在解读亚组分析结果时需保持谨慎。我们进行了一些观察，似乎在基线以及治疗后HDL-C水平更高的患者中，瑞舒伐他汀的作用更好。我们还不清楚这是否反映了HDL-C功能活性的差异。这些数据可能反映了更多的功能性HDL-C促使病变更多的逆转，我们需要做更多工作以更好地理解这些发现。
　　International Circulation: In statin treatment， we know the most important thing is to reach the LDL target and this year’s ESC/EAS Joint Guidelines on dyslipidemia management recommended even lower LDLc levels. For example， for patients at very high risk， the goal is <70mg/dl or at least a 50% reduction. What are your thoughts on strategies using different statin agents in clinical practice in order to achieve these goals?