Pareek A, Zawar S D, Salagre S B, Chandurkar N B, Karnik N D
Medical Affairs and Clinical Research, Ipca Laboratories Ltd., 142 AB, Kandivli Industrial Estate, Kandivli (West), Mumbai 400067, India.
Eur J Med Res. 2009 Jul 22;14(7):297-303. doi: 10.1186/2047-783x-14-7-297.
High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-to-moderate essential hypertension.
Total 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg.
The study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorthalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (Na (+), K(+), Cl(-)) and fasting blood sugar, evident across the treatment groups.
Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.
高血压是最重要的危险因素之一，直接导致心血管疾病发病率和死亡率上升。主要目的是评估美托洛尔缓释片/氯噻酮与美托洛尔缓释片/氢氯噻嗪相比，在降低收缩压和舒张压方面的疗效。次要目的是比较反应率，并评估研究药物在轻至中度原发性高血压患者中的耐受性。
总共130名符合条件的患者（65名：美托洛尔缓释片25 mg/氯噻酮6.25 mg；65名：美托洛尔缓释片25 mg/氢氯噻嗪12.5 mg）被纳入这项随机、对照、多中心、为期12周的研究。每组62名患者完成了研究。治疗4周后，氯噻酮6.25 mg联合组的无反应者转用美托洛尔缓释片50 mg/氯噻酮12.5 mg，氢氯噻嗪12.5 mg联合组的无反应者升级为美托洛尔缓释片50 mg/氢氯噻嗪12.5 mg。
研究治疗组在人口统计学和基线疾病特征方面具有可比性。两种起始治疗方案在治疗4周后的收缩压平均下降幅度（p = 0.788）、舒张压平均下降幅度（p = 0.939）和反应率（p = 1.0）方面具有可比性。在12周结束时，两种强化治疗方案的收缩压平均下降幅度（p = 0.277）和舒张压平均下降幅度（p = 0.507）也相似。然而，与氢氯噻嗪12.5 mg/美托洛尔缓释片50 mg组相比，氯噻酮12.5 mg/美托洛尔缓释片50 mg组对治疗有反应的患者数量明显更多（p = 0.045）。所有报告的不良事件均为轻至中度。各治疗组的电解质（Na(+)、K(+)、Cl(-)）和空腹血糖均无临床显著变化趋势。
氯噻酮与美托洛尔缓释片联合使用与广泛使用的美托洛尔缓释片/氢氯噻嗪联合使用一样有效且耐受性良好，从而提供了一种替代治疗选择。
