<International Circulation>: In order to improve blood pressure control， it seems appropriate to combine drugs with different mechanisms to achieve target blood pressure. Which class of drugs should be used as the basis of combination therapy to cope with resistant hypertension?

   《国际循环》：为改善血压控制，联合应用不同机制的抗高血压药物以达到目标血压的策略看来是合理的。对于治疗顽固性高血压，哪种药物应当被用作联合治疗的基础？

    Dr Parra: By the mere definition of resistant hypertension， these patients are going to be on at least three medications and those should be three medications from three different classes. Then the question arises: What do we do next? There are probably two or three things that we really need to look at in these individuals. Intensification of diuretic therapies is very important and you need to look at the diuretic that you are using. Chlorthalidone really should be the thiazide-type diuretic we are using over hydrochlorothiazide. In the United States， hydrochlorothiazide was the number one prescribed drug in 2008， accounting for over 131 million prescriptions， but of that， 97% of the prescriptions for hydrochlorothiazide were at a dose of 12.5 to 25mg which probably isn’t sufficient enough. There are also issues with chlorthalidone being a better hypertensive agent because it has a longer duration of action and more persistent reduction of blood pressure over a 24-hour period. So the thiazide-type diuretic that should be the one of choice is that of chlorthalidone. The other thing we look at when we are treating resistant hypertension are the mineralocorticoid receptor antagonists， drugs such as spironolactone， which have been demonstrated to be effective in patients with resistant hypertension regardless of what their aldosterone levels are. It was once thought that patients responded best to spironolactone if they had primary aldosteronism or an elevated aldosterone state but that has been found to be no longer the case and in a study of true resistant hypertension it was confirmed by 24-hour ambulatory blood pressure monitoring， patients had a wonderful response to a spironolactone dose of 25-50 mg regardless of their aldosterone levels. Of note in that study was that there wasn’t really any value in pushing doses up to 100mg. So the correct thiazide-type diuretic and the use of a mineralocorticoid receptor are probably two of the key things that will help with resistant hypertension， as well as identifying new methods to further refine the type of blood pressure medications we are using.

    Parra博士：单纯根据顽固性高血压的定义，这些患者至少要接受3种药物治疗，且应该是3个不同种类的3种药物。然后，问题就出现了：接下来我们应该做什么？在这些个体中可能有2或3件事情我们必须注意。：强化利尿剂治疗是非常重要的，而且你需要关注你正在应用的利尿剂；我们对噻嗪类利尿剂氯噻酮的应用应该超过氢氯噻嗪。在美国，氢氯噻嗪是2008年处方排名第一的药物，超过1.31亿次，但其中97%的氢氯噻嗪处方都是12.5 mg~25 mg的剂量，这可能并不足够。氯噻酮作为一个更好的高血压药物也有问题，其作用时间更长，在24小时期内能持续降低血压。因此选择噻嗪类利尿剂时应该选氯噻酮。在顽固性高血压治疗中，我们关注的另一件事情是盐皮质激素受体拮抗剂，如安体舒通等药物，该药已经被证实不管其醛固酮水平如何，在顽固性高血压患者中都是有效的，。我们一度认为如果患者有原发性醛固酮增多症或醛固酮水平升高，其对安体舒通的反应最好，但这但现在发现事实并非如此。在一项真性顽固性高血压的研究中， 24小时动态血压监测证实，无论其醛固酮水平如何，患者对25 mg ~50 mg剂量的安体舒通反应良好。在该项研究中值得注意的是，将剂量提高至100 mg并无任何价值。因此，合适的噻嗪类利尿剂和盐皮质激素受体拮抗剂的应用很可能是有助于治疗顽固性高血压、以及找到新方法以进一步简化我们正在应用的降压药物种类的两件关键的事情。