Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Italy.
J Hypertens. 2011 Mar;29(3):600-9. doi: 10.1097/HJH.0b013e328342ef04.
Guidelines on hypertension regard combinations between two antihypertensive drugs to be the most important treatment strategy. Because of the complementary mechanism of action and the evidence of cardiovascular protective effects they include the combination of a calcium antagonist and an angiotensin receptor antagonist among the priorital ones to employ.
To determine in hypertensive patients at high cardiovascular risk whether combining Nifedipine GITS at low dose and telmisartan reduced ambulatory and clinic blood pressure (BP) more than the combination components, controlled BP early after treatment initiation and allowed to also obtain a better long-term BP control compared to initiating treatment with the combination components and moving to the combination later.
Four hundred and five patients with a clinic SBP ≥ 135 mmHg and with diabetes, a metabolic syndrome or organ damage were randomized to once-a-day telmisartan 80 mg, nifedipine GITS 20 mg or the combination of the two drugs in a 1: 1: 2 ratio for 8 weeks in the context of a multicenter double-blind study design. Patients on monotherapy were then moved to combination treatment and all three groups were followed for an additional 16-week period. Both 24-h and clinic BP were measured before treatment and at various times during treatment.
In the per-protocol patients (n = 327), baseline demographic and clinical characteristics were similar between the three groups. Baseline 24-h SBP values were 136.2 ± 11.6 mmHg (mean ± SD), 137.2 ± 12.5 mmHg and 136.8 ± 11.7 mmHg in the telmisartan monotherapy, nifedipine GITS monotherapy and combination therapy, respectively. The corresponding clinic values were 151.7 ± 11.8, 151.3 ± 11.9 and 151.1 ± 11.8 mmHg, respectively. All treatments lowered 24-h SBP significantly (P < 0.0001) but combination treatment (8 weeks) reduced it significantly more than monotherapies (10.8 ± 0.8 vs. 6.6 ± 1.1 mmHg and 8.0 ± 1.2 mmHg; P = 0.001 and 0.037). Similar data were obtained for clinic SBP for which the combination showed a significantly greater BP reduction (12.6 ± 0.6 vs. 8.6 ± 0.7 mmHg and 9.3 ± 0.8 mmHg; P = 0.003 and 0.024) also after 2 weeks of treatment. Moving from monotherapy to combination therapy increased the antihypertensive effect and made both ambulatory and clinic SBP superimposable in the three groups after 16 and 24 weeks of treatment. Similar findings were obtained for DBP.
Combination treatment with nifedipine GITS low dose and telmisartan provides a greater and earlier clinic and ambulatory BP reduction than the combination components in monotherapy. Initiating treatment with the combination did not result in any better longer term BP control compared to starting treatment with monotherapy and moving to the combination later.
高血压指南认为将两种降压药物联合使用是最重要的治疗策略。由于互补的作用机制和心血管保护作用的证据，钙拮抗剂和血管紧张素受体拮抗剂的联合使用被认为是优先选择的方案之一。
在心血管风险较高的高血压患者中，确定低剂量硝苯地平 GITS 和替米沙坦联合使用是否比联合用药的单一成分更能降低动态和诊室血压，以及在治疗早期控制血压，并在与单一成分联合治疗后转为联合治疗相比，是否能获得更好的长期血压控制。
将 405 例诊室收缩压（SBP）≥135mmHg 且患有糖尿病、代谢综合征或器官损害的患者随机分为每日一次替米沙坦 80mg、硝苯地平 GITS 20mg 或两者 1:1:2 的比例联合治疗，持续 8 周，在一项多中心、双盲研究设计中。单药治疗的患者随后转为联合治疗，所有三组患者均再随访 16 周。在治疗前和治疗过程中的不同时间测量 24 小时和诊室血压。
在符合方案的患者（n=327）中，三组患者的基线人口统计学和临床特征相似。基线 24 小时 SBP 值分别为替米沙坦单药组 136.2±11.6mmHg（均值±标准差）、硝苯地平 GITS 单药组 137.2±12.5mmHg 和联合治疗组 136.8±11.7mmHg。相应的诊室值分别为 151.7±11.8mmHg、151.3±11.9mmHg 和 151.1±11.8mmHg。所有治疗均显著降低 24 小时 SBP（P<0.0001），但联合治疗（8 周）比单药治疗（6.6±1.1mmHg 和 8.0±1.2mmHg；P=0.001 和 0.037）降低更显著。诊室 SBP 也有类似的数据，联合治疗组的降压效果更显著（12.6±0.6mmHg 比 8.6±0.7mmHg 和 9.3±0.8mmHg；P=0.003 和 0.024），在治疗 2 周后也有同样的结果。从单药治疗转为联合治疗后，三组的降压效果均增加，24 周和 16 周的诊室和 24 小时 SBP 重叠。DBP 也有类似的发现。
硝苯地平 GITS 低剂量和替米沙坦联合治疗可显著降低诊室和动态血压，且降压幅度大于单药治疗的联合成分。与起始单药治疗后转为联合治疗相比，起始联合治疗并不能获得更好的长期血压控制。
