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Abstract：
The main objective of fixed dose combination therapy for hypertension is to improve blood pressure (BP) control with lower, better tolerated dosages of 2 antihypertensives rather than higher dosages of a single agent. Felodipine and metoprolol lower BP via different, but complementary, mechanisms and controlled release formulations of these 2 drugs are available as a fixed dose combination, felodipine/metoprolol. In clinical trials in patients with hypertension, felodipine/metoprolol was significantly more effective than placebo and the respective monotherapies administered at the same dosages. Mean BP was reduced to < 155/90 mm Hg in patients treated with combination therapy and controlled in approximately 70% of patients. In one study that titrated dosages to effect, fewer felodipine/metoprolol than felodipine or metoprolol monotherapy recipients required dosage increases to achieve BP control (45 vs 60 and 67%, respectively). Data from double blind comparative studies show that the antihypertensive efficacy of felodipine/metoprolol 5 to 10/50 to 100 mg/day is significantly greater than that of enalapril monotherapy or captopril plus hydrochlorothiazide and equivalent to nifedipine/atenolol and amlodipine. In comparisons with enalapril, fewer felodipine/metoprolol than enalapril recipients required dosage titration to achieve BP control. Compared with amlodipine, felodipine/metoprolol significantly reduced mean 24-hour average BP (8.9/5.5 vs 14.4/9.5 mm Hg after 6 weeks; p < 0.001). Both treatments preserved diurnal rhythm. Long term follow-up studies show that the antihypertensive effect of felodipine/metoprolol occurs mostly during the first month of treatment with small additional decreases in BP being observed in the second and third months, and a relatively constant effect thereafter. According to a validated questionnaire, quality of life was relatively similar during 12 weeks treatment with felodipine/metoprolol, enalapril or placebo. In a retrospective pharmacoeconomic analysis conducted in Sweden, felodipine/metoprolol was more cost effective than enalapril as initial treatment for hypertension. Peripheral oedema, headache and flushing were the most commonly reported adverse events with felodipine/metoprolol and felodipine monotherapy, whereas dizziness, fatigue, headache and respiratory infection were more frequent with metoprolol monotherapy. Dose-dependent adverse events such as oedema may occur less often in patients taking lower dosages in combination than in those taking higher dosages of felodipine monotherapy. Thus, patients with hypertension treated with felodipine/metoprolol experience greater control of BP, with less need for dosage titration, than those treated with felodipine, metoprolol or enalapril monotherapy. Importantly this greater efficacy does not appear to be associated with a higher incidence of adverse events relative to monotherapy. Additionally, in short term studies felodipine/metoprolol had a similar (minimal) effect on QOL to enalapril monotherapy but was more cost effective.
摘要：
高血压固定剂量联合治疗的主要目的是改善血压(BP)控制,2种抗高血压药的耐受性更好，而不是单一药物的更高剂量。非洛地平和美托洛尔通过不同的方式降低血压，但是互补的，这两种药物的机制和控释制剂可作为固定剂量组合使用，非洛地平/美托洛尔。在高血压患者的临床试验中，非洛地平/美托洛尔比安慰剂和以相同剂量施用的各自单一疗法显着更有效。在接受联合治疗的患者中,平均BP降低至<155/90mmHg,并且在约70%的患者中得到控制。在一项滴定剂量的研究中，非洛地平/美托洛尔少于非洛地平或美托洛尔单药治疗接受者，需要增加剂量以实现BP控制（45vs60％和67％，分别)。来自双盲比较研究的数据表明，非洛地平/美托洛尔5至10/50至100mg/天的抗高血压功效明显高于依那普利单药或卡托普利加氢氯噻嗪，相当于硝苯地平/阿替洛尔和氨氯地平。与依那普利相比，非洛地平/美托洛尔比依那普利接受者少,需要剂量滴定来实现BP控制.与氨氯地平相比,非洛地平/美托洛尔可显著降低24小时平均血压(6周后8.9/5.5vs14.4/9.5mmHg;p<0.001)。两种治疗方法都保持了昼夜节律。长期随访研究表明，非洛地平/美托洛尔的降压作用主要发生在治疗的第一个月，在第二个月和第三个月观察到血压的小幅额外下降。以及此后相对恒定的效果。根据一份经过验证的问卷，在使用非洛地平/美托洛尔的12周治疗期间，生活质量相对相似，依那普利或安慰剂。在瑞典进行的回顾性药物经济学分析中，非洛地平/美托洛尔作为高血压的初始治疗比依那普利更具成本效益。周围性水肿，头痛和潮红是非洛地平/美托洛尔和非洛地平单药治疗最常见的不良事件。而头晕，疲劳,美托洛尔单药治疗时头痛和呼吸道感染更为常见.与服用较高剂量的非洛地平单一疗法的患者相比，服用较低剂量的患者的剂量依赖性不良事件如水肿的发生频率较低。因此，使用非洛地平/美托洛尔治疗的高血压患者的血压得到了更好的控制，对剂量滴定的需求较少，比用非洛地平治疗的人多，美托洛尔或依那普利单药治疗。重要的是，相对于单一疗法，这种更大的疗效似乎与更高的不良事件发生率无关。此外,在短期研究中,非洛地平/美托洛尔对生活质量的影响与依那普利单药治疗相似(最小),但更具成本效益.
