First Cardiology Clinic, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece.
Department of Cardiology, Helena Venizelou Hospital, Athens, Greece.
Pharmacol Res. 2017 Nov;125(Pt B):266-271. doi: 10.1016/j.phrs.2017.09.011. Epub 2017 Sep 20.
Combination treatment of hypertension has been introduced almost 50 years ago, because of the marked blood pressure (BP) elevation of recruited patients in the early randomized controlled trials of BP lowering. However, in all subsequent trials combination treatment was per protocol anticipated irrespectively of the initial randomized treatment to ensure either a desirable BP lowering or a comparable level of BP reduction among arms. Beyond clinical trials, combination treatment is mainly used in the clinical practice to reinforce ongoing single-agent treatment to achieve hypertension control. Renin-angiotensin system inhibiting drugs are the cornerstone of combination treatment of hypertension because they have been repeatedly tested in clinical trials in combination with other agents either from the beginning or during the follow-up. Effective BP lowering following combination treatment depends on the activation of complementary pathophysiological pathways but different agents can stimulate a common mode of action more effectively. The rate of adverse events following combination treatment may be reduced because effects of each agents are reciprocally counterbalanced. Nevertheless, aggressive BP lowering independently of the implemented combination is associated with increase of treatment discontinuations. In the management of resistant hypertension, a fourth-line agent used on top of the failing triple (diuretic-based) combination is effective to control hypertension only in 50% of patients. At present, it is questioned whether combination treatment of hypertension should be used alternatively to monotherapy in newly-diagnosed hypertensive patients without marked BP elevation or at low cardiovascular risk. Selection between free and fixed-dose combination treatment should be individualized depending on clinical criteria.
联合治疗高血压的方法在大约 50 年前就已经出现了，因为在早期的降压随机对照试验中，入选的患者血压明显升高。然而，在随后的所有试验中，无论最初的随机治疗如何，联合治疗都是按照方案进行的，目的是确保降压效果理想或各治疗组的血压降低水平相当。临床试验之外，联合治疗主要用于临床实践，以加强正在进行的单一药物治疗，从而实现高血压控制。肾素-血管紧张素系统抑制药物是高血压联合治疗的基石，因为它们已在临床试验中与其他药物联合使用，无论是从一开始还是在随访期间。联合治疗后血压的有效降低取决于互补病理生理途径的激活，但不同的药物可以更有效地刺激共同的作用模式。联合治疗后不良事件的发生率可能降低，因为每个药物的作用相互抵消。然而，不考虑实施的联合治疗而进行的积极降压与治疗中断率的增加有关。在难治性高血压的治疗中，在失败的三联（基于利尿剂）组合之上使用第四线药物，仅能有效控制 50%的患者的高血压。目前，人们质疑对于没有明显血压升高或心血管风险低的新诊断高血压患者，是否应将高血压的联合治疗替代单药治疗。应根据临床标准个体化选择自由配方和固定剂量联合治疗。
