请您谈谈直接肾素抑制剂在降压和心肾保护方面的作用机理。肾素抑制剂具有心肾保护作用,其具体临床表现是什么?血浆肾素活性(PRA)是心血管事件的重要预测因子,阿利吉仑(Rasilez®)可以有效降低PRA,这种作用会带来怎样的远期临床效果呢?
International Circulation: We know that the effect of aliskiren on organ damage and clinical outcomes is being assessed in clinical trials such as the ASPIRE Higher program. Previous clinical trials such as ALLOFT, AVOID, ALAY, etc, have also assessed such parameters. What do you predict will be the result of the ASPIRE HIGHER trial? Do you think it will confirm some of the earlier trial results or what is your view?
国际循环: 我们知道,阿利吉仑对器官损伤的作用,而诸如ASPIRE HIGHER项目等临床试验中则正在对临床转归进行评价。已有的ALLOFT、AVOID、 ALAY等临床试验也已对此类参数进行了评估。您预测ASPIRE HIGHER试验将会出现怎样的结果?您是否认为它将证实一些早期试验的结果,或者您的观点是什么?
Gonzalez Juanatey: Probably the ASPIRE HIGHER program will give us more information and give us new data for the ongoing many clinical trials with these drugs. Probably one of the facts that limit the value of the combined therapy with ACE-inhibitor B is the tremendous increasing in plasma renin activity. When you combine an ACE inhibitor B, the plasma renin activity increases so much. This may be responsible for the low effect in clinical practice of such combinations. If you combine an ACE inhibitor B in high-risk patients with and elevated renin activity inhibitor like aliskiren, then probably blocking of renin activity. On the other hand, the beneficial effects of the ACE or ARB drugs may be more reasonable and a better clinical judgment for combining therapy to achieve clinical protection as we have seen in AVOID, cardio-protection as we have seen in ALAY, and protection for heart failure as we have seen in ALOFT. The ASPIRE HIGHER program will probably give us new data to reinforce the idea that combined therapy of one blocker of the renin-angiotensin system and an ACE inhibitor may be the best combination therapy for promoting health vascular and kidney function.
Gonzalez Juanatey教授: 很可能ASPIRE HIGHER项目将为我们提供更多信息,并为正在进行的诸多此类药物临床试验提供新的数据。限制与ACE抑制剂联合应用的原因是ACE抑制剂可以导致血浆肾素活性的极大增强。当联合使用一种ACE抑制剂时,血浆肾素活性增强是如此之大。这可能是这种联合用药的临床实践中效果不佳的原因。如果在肾素活性升高的高危患者中将一种ACE抑制剂和一种其他阻断剂联合使用,例如阿利吉仑,那么很可能可以阻断肾素活性。另一方面, ACEI或者ARB类药物的有益效应可能更合理,是更好的联合治疗的选择,从而获得我们在AVOID试验中所见到的临床保护作用、在ALAY试验中所见到的心脏保护作用、以及在ALOFT试验中所见到的心衰保护作用。用肾素-血管紧张素系统的一种阻断剂和一种ACE抑制剂联合治疗可能是促进血管和肾脏功能健康的最佳联合治疗方案,ASPIRE HIGHER项目将可能为我们提供可以强化这一观点的新数据。