Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA.
J Hypertens. 2013 Aug;31(8):1692-701. doi: 10.1097/HJH.0b013e32836157be.
Although fixed-dose combination drug therapy is commonly used to treat hypertension, the efficacy of head-to-head comparisons of dual fixed-dose combinations has not been well described. We hypothesized that when used in combination with an angiotensin receptor blocker (ARB) olmesartan medoxomil, hydrochlorothiazide (HCTZ) will be as effective as the dihydropyridine calcium channel blocker (CCB) amlodipine to lower both clinic and 24-h ambulatory blood pressure (BP). Furthermore, we hypothesized that response to ARB along with HCTZ or ARB along with CCB may be heterogeneous depending on clinical characteristics.
An individual-level meta-analysis was performed among 559 individuals treated with dual combination therapy in five trials. A forced titration scheme was used in each of these trials and blood BP was measured both in the clinic and outside using 24-h ambulatory BP monitors.
The mean age was 62 years, 55% were men, 46% had diabetes mellitus, 17% were black, clinic BP averaged 159.5/89.5 mmHg and 24-h ambulatory BP 145.0/82.5 mmHg. Overall, baseline-adjusted lowering of mean 24-h ambulatory BP was 22.0/11.7 mmHg. BP reductions were similar between ARB along with HCTZ and ARB along with CCB groups. However, clinic BP was lowered 4.3/1.8 mmHg more with ARB along with CCB combination (28.4/13.0 mmHg drop) than with ARB along with HCTZ combination (24.1/11.2 mmHg drop). The white coat effect (WCE) was therefore mitigated 3.8/1.7 mmHg more with ARB along with CCB combination. Heterogeneity in ambulatory BP response was noted. Compared with men, women had a greater ambulatory and clinic BP lowering with either combination. ARB along with HCTZ produced a greater BP-lowering effect among men, elderly, nonobese and nondiabetic. On the contrary, ARB along with CCB produced a greater BP-lowering effect among women, young, obese and diabetic individuals. This heterogeneity in response was often undetectable with clinic BP measurements. In multivariable analysis, sex and diabetes mellitus remained independent measures of heterogeneity.
Overall, the combination of olmesartan and HCTZ is as effective as olmesartan and CCB in lowering 24-h, daytime, and night-time ambulatory BP. However, greater lowering is noted with the olmesartan and CCB combination for clinic BP. Thus, out-of-office BP monitoring is necessary to provide better assessment of overall BP and response to treatment. Women and diabetic individuals may have slightly better 24-h ambulatory BP response with the olmesartan and CCB combination therapy.
虽然固定剂量联合药物治疗常用于治疗高血压，但双联固定剂量联合治疗的疗效尚未得到很好的描述。我们假设，当与血管紧张素受体阻滞剂（ARB）奥美沙坦酯联合使用时，氢氯噻嗪（HCTZ）将与二氢吡啶钙通道阻滞剂（CCB）氨氯地平一样有效，可降低诊所和 24 小时动态血压（BP）。此外，我们假设，ARB 联合 HCTZ 或 ARB 联合 CCB 的反应可能因临床特征而异。
对五项试验中接受双联联合治疗的 559 名个体进行了个体水平的荟萃分析。这些试验中的每一项都采用了强制滴定方案，在诊所和使用 24 小时动态血压监测仪在外部测量血压。
平均年龄为 62 岁，55%为男性，46%患有糖尿病，17%为黑人，诊所血压平均为 159.5/89.5mmHg，24 小时动态血压为 145.0/82.5mmHg。总体而言，平均 24 小时动态血压的基线调整后降低了 22.0/11.7mmHg。ARB 联合 HCTZ 组和 ARB 联合 CCB 组的血压降低情况相似。然而，ARB 联合 CCB 联合治疗组的诊所血压降低了 4.3/1.8mmHg（28.4/13.0mmHg 下降），高于 ARB 联合 HCTZ 联合治疗组（24.1/11.2mmHg 下降）。因此，ARB 联合 CCB 联合治疗组的白大衣效应（WCE）减轻了 3.8/1.7mmHg。注意到动态血压反应的异质性。与男性相比，女性在任何一种联合治疗中都有更大的动态和诊所血压降低。ARB 联合 HCTZ 对男性、老年人、非肥胖和非糖尿病患者的降压效果更好。相反，ARB 联合 CCB 对女性、年轻人、肥胖和糖尿病患者的降压效果更好。这种反应的异质性通常在诊所血压测量中无法检测到。在多变量分析中，性别和糖尿病仍然是异质性的独立衡量标准。
总的来说，奥美沙坦酯联合 HCTZ 与奥美沙坦酯联合 CCB 一样有效，可降低 24 小时、白天和夜间动态血压。然而，奥美沙坦酯联合 CCB 组的诊所血压降低幅度更大。因此，需要进行非诊所血压监测，以更好地评估总体血压和治疗反应。女性和糖尿病患者可能对奥美沙坦酯联合 CCB 治疗有更好的 24 小时动态血压反应。
