Kreutz R
Institute of Clinical Pharmacology and Toxicology, Charité, Universtitätsmedizin - Berlin, Germany.
Vasc Health Risk Manag. 2011;7:183-92. doi: 10.2147/VHRM.S16852. Epub 2011 Mar 29.
Combination therapy is an effective strategy to increase antihypertensive efficacy in those patients with poor blood pressure (BP) control. In order to achieve BP targets, at least 75% of patients may require combination therapy, and European guidelines advocate this approach, particularly in those patients with a high cardiovascular risk. Evidence from large, randomized controlled trials, and the European hypertension treatment guidelines is supportive of the use of an angiotensin receptor blocker (ARB) with a calcium channel blocker (CCB). Fixed-dose combination formulations of olmesartan medoxomil, an ARB, and the CCB amlodipine are approved in several European countries for patients with essential hypertension. The olmesartan/amlodipine combination has demonstrated greater efficacy than its component monotherapies in reducing BP in patients with mild-to-severe hypertension. Significantly greater reductions in seated diastolic BP were observed between baseline and after eight weeks of treatment with olmesartan/amlodipine, compared with equivalent doses of olmesartan or amolodipine monotherapy (P < 0.001), in the factorial Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial. About 85% of the maximal BP reductions after the 8-week treatment period were already observed after two weeks. Uptitration as necessary, with or without hydrochlorothiazide, allowed the majority of patients to achieve BP control in a 44-week open-label extension treatment period to the COACH trial. The use of olmesartan/amlodipine allowed up to 54% of patients, with previously inadequate responses to amlodipine or olmesartan monotherapy, to achieve their BP goals. Data from post-registration studies using tight BP control and forced titration regimens have further demonstrated the high efficacy of olmesartan/amlodipine in achieving BP goal rates. Moreover, consistent reductions in BP were observed over the 24-hour dosing interval using ambulatory measurements. Olmesartan/amlodipine was generally well tolerated over the short- and long-term, with a lower frequency of peripheral edema with olmesartan/amlodipine 40/10 mg than with amlodipine 10 mg monotherapy.
联合治疗是提高血压(BP)控制不佳患者降压疗效的有效策略。为了实现血压目标,至少75%的患者可能需要联合治疗,欧洲指南提倡这种方法,尤其是在心血管风险高的患者中。大型随机对照试验以及欧洲高血压治疗指南的证据支持使用血管紧张素受体阻滞剂(ARB)与钙通道阻滞剂(CCB)联合。在几个欧洲国家,ARB奥美沙坦酯与CCB氨氯地平的固定剂量复方制剂已被批准用于原发性高血压患者。奥美沙坦/氨氯地平联合用药在降低轻至重度高血压患者血压方面已显示出比其单药成分更高的疗效。在奥美沙坦酯与苯磺酸氨氯地平控制高血压的析因试验(COACH试验)中,与等量的奥美沙坦或氨氯地平单药治疗相比,在基线和奥美沙坦/氨氯地平治疗8周后,坐位舒张压的显著降低更为明显(P<0.001)。在8周治疗期后,约85%的最大血压降幅在两周后就已出现。在COACH试验为期44周的开放标签延长期治疗中,根据需要进行滴定,无论是否加用氢氯噻嗪,大多数患者都实现了血压控制。使用奥美沙坦/氨氯地平使多达54%之前对氨氯地平或奥美沙坦单药治疗反应不足的患者实现了血压目标。使用严格血压控制和强制滴定方案的注册后研究数据进一步证明了奥美沙坦/氨氯地平在实现血压达标率方面的高效性。此外,通过动态测量观察到在24小时给药间隔内血压持续降低。奥美沙坦/氨氯地平在短期和长期内总体耐受性良好,与氨氯地平10mg单药治疗相比,奥美沙坦/氨氯地平40/10mg外周水肿的发生率更低。