临床医生和患者应更关注高血压治疗的目的,是要预防心脏病发作、卒中和死亡,而不是表面的血压数值的降低(尽管这也很重要)。这也是我们这些年来坚持给予患者(即使他们没有症状)这类药物的原因。
Alistair Scott Hall,英国利兹大学临床心脏病学教授,流行病学主任。
International Circulation: Considering the superiority of the ACE inhibitors and ARBs in blocking RAS, should the optimal treatment for hypertensive patients be high dose ARBs and ACE inhibitors or a low dose combination?
《国际循环》:考虑到ACEI和ARB药物在阻断RAS系统方面的优越性,高血压患者应该选择单独大剂量ARB/ACEI还是小剂量ACEI和ARB联合应用作为最佳治疗?
Dr Hall: Firstly, I don’t see the ACE inhibitors and ARBs as interchangeable and equally superior because they are not. If one looks at meta-analyses of ACE inhibitors, you see a reduction of stroke, heart attack and death. If you look at a meta-analysis of ARBs against placebo, you see benefits for stroke risk but not heart attack or death. So they are not equivalent at all. Most people believe ARBs to be better tolerated, but if you look at the relative doses that have been used in comparative studies such as VALIANT and ONTARGET, the tolerability is similar. They are both equally tolerated but the efficacy is greater with ACE inhibitors. The ACE inhibitors should be at the cornerstone of hypertension and cardiovascular protection management; ARBs should not.
Dr Hall:首先,我不认为ACEI和ARB之间是可以互换的,也并不认为两者同样出众。关于ACEI的荟萃分析显示,ACEI可使卒中、心脏病发作和死亡减少; 但从ARB与安慰剂对照的荟萃分析中只能看到卒中风险获益,而不包括心脏病发作和死亡。所以,二者根本就不同。大多数人认为ARB的耐受性更好,但实际上,回顾两者相关剂量的比较研究(如VALIANT 和ONTARGET),其耐受性类似,但ACEI的疗效更佳。因此,ACEI应被视为高血压治疗和心血管系统保护的基石,而不是ARB。
International Circulation: How should physicians choose between ACE inhibitors and ARBs?
《国际循环》:那么临床医生在ACEI和ARB之间如何选择呢?
Dr Hall: If the physicians care, as do the patients, about the reasons that we treat blood pressure, it is not to lower the number that we measure (although that is still important), it is to prevent heart attack, stroke and death. That is why we prescribe these medications to people for years and years even they have no symptoms and we tell them that we are preventing a major event in the future. If we are not preventing that major event then there is a real question that why we would use that medication. Regarding ARBs, they are effective at reducing blood pressure and stroke but not for coronary artery disease and death overall. That is based on studies against placebo, not against other active therapies. ACE inhibitors therefore are superior although they are of an older class of drugs and they are not promoted and have been thought as a downturn in most people’s minds. I don’t think that is based on data; I think it is based on marketing.
Dr Hall:临床医生和患者应更关注高血压治疗的目的,是要预防心脏病发作、卒中和死亡,而不是表面的血压数值的降低(尽管这也很重要)。这也是我们这些年来坚持给予患者(即使他们没有症状)这类药物的原因。如果不能预防主要不良事件的发生,那是否还要使用这种药物就成了一个问题。ARB能有效降低血压和减少卒中,但并不能使冠心病患者获益益也不能降低总体死亡率。因此,即使ACEI是一类比较老的药物,在很多人心目中的地位在下降而不再大力推荐,但ACEI药物依然很优秀。我并不认为使用下降是基于统计数据的判断,而是基于市场营销的结果。
International Circulation: ARBs are known for their protective effect on the kidneys however they may cause hyperkalemia in patients with impaired renal function. How should these patients be handled in these situations?
《国际循环》:已知ARB对肾脏有保护作用,但在肾功能受损的患者中可能会导致肾高钾血症。这些患者应该如何处理?
Dr Hall: Actually both ACE inhibitors and ARBs can raise potassium and the combination raises potassium even more. They both have their final action by preventing aldosterone release. Aldosterone creates sodium retention and potassium excretion so if you block it, you get potassium retention, sodium excretion. So these drugs can raise potassium which can be problematic especially in combination with other drugs that can raise potassium such as spironolactone. The way to manage it would be to avoid the combinations of those medicines. In renal failure, you are already going to have raised potassium because of the kidney dysfunction. Most renal patients will tolerate surprisingly high potassium levels because it is chronically high, so the way renal patients are managed is slightly different to other patients. Normally it would be shown by continuous monitoring of kidney function which renal patients have at a renal clinic but in that setting, I would be more tolerant of raised potassium if I felt kidney function was being protected.
Dr Hall:ACEI和ARB都会升高血钾,二者均能通过减少醛固酮的释放来发挥作用,联合应用时升血钾作用更强。醛固酮的作用是引起钠潴留和钾的排泄,所以拮抗醛固酮会保钾排钠。ACEI和ARB的保钾作用可能就会带来一些问题,尤其是在与其它会升高血钾(如螺内酯)的药物联用时。因此,应该尽量避免ACEI/ARB与保钾类药物联用。肾功能衰竭时,肾功能不全会导致高血钾水平,长期、慢性进展的高钾血症使大多数肾病患者能耐受非常高的钾水平。因此,肾病患者的治疗与其他患者略有不同。通常情况下,肾病患者应在肾内科门诊持续监测肾脏功能,在达到保护肾功能的前提下,我会适当放宽血钾高水平。
International Circulation: Several guidelines have set the blood pressure targets for hypertensive patients with chronic kidney disease to below 130/80 which has been controversial. A few trials such as AASK come out negative. Is it necessary to control blood pressure to lower than 130/80 especially in those patients?
《国际循环》:一些指南将合并慢性肾脏疾病的高血压患者的目标血压定为低于130/80 mm Hg,但AASK等临床试验所得出的结果并不不支持这种观点,所以这一提议一直存在争议。你认为在此类患者中将血压控制低于130/80 mm Hg有必要吗?
Dr Hall: 130/80 is a perfect blood pressure for all of us and we should all try to stay there as long as we can through natural means, and if need be, through drug therapy. The problem with chronic kidney disease patients is that their entire blood pressure control is abnormal. The real question for them is not whether we should get that low but whether we can get that low. Often that is impossible especially in an older patient. We also need to have a patient’s agreement to take tablets; if we are using such high doses and so many medications that we are creating a side effect profile that is unpleasant to them, then we may have worse blood pressure control. It is a compromise, a negotiation between patient and doctor. We should aim in that direction but we have to choose therapy that is going to be tolerated.
Dr Hall:130/80 mm Hg对所有人来说都是一个完美的血压水平,我们应该用各种自然手段尽力维持这一水平,如果有需要还可以应用药物。慢性肾脏疾病患者的血压控制不佳。对于这些患者,真正的问题不在于是否应该达到这样低的血压水平,而是是否能够达到这一水平。这通常是很困难的,特别是老年患者。治疗方案需得到患者的同意,由于担心大剂量、多种药物可能带来的副作用,患者的血压控制会更差。以这个130/80 mm Hg为目标,我们最终需要选择患者能够耐受的治疗方案。