The University of Chicago Medicine, Chicago, IL 60637, USA.
Am J Med. 2012 Dec;125(12):1229.e1-1229.e10. doi: 10.1016/j.amjmed.2012.05.023. Epub 2012 Aug 30.
Chlorthalidone has proven efficacy to reduce cardiovascular morbidity and mortality, yet it is infrequently used in practice. This study provides a direct comparison of chlorthalidone with hydrochlorothiazide, each combined with the angiotensin receptor blocker azilsartan medoxomil, on blood pressure reduction and control rates.
This is a randomized, double-blind, titrate-to-target blood pressure trial comparing the single-pill combination of azilsartan medoxomil and chlorthalidone versus co-administration of azilsartan medoxomil and hydrochlorothiazide in participants with stage 2 primary hypertension. After 2 weeks of treatment with azilsartan medoxomil 40 mg alone, all participants also received 12.5 mg of diuretic for 4 weeks (up to week 6) and were titrated to 25 mg for another 4 weeks (up to week 10) if they failed to achieve target blood pressure. The primary end point was change in clinic systolic blood pressure. Target blood pressure was defined as clinic blood pressure <140/90 mm Hg for participants without diabetes or chronic kidney disease or <130/80 mm Hg for participants with diabetes or chronic kidney disease.
The mean age of the 609 participants was 56.4 years, and the mean baseline clinic blood pressure was 164.6/95.4 mm Hg. The primary end point analysis at week 6 demonstrated a greater reduction of clinic systolic blood pressure for the chlorthalidone (-35.1 mm Hg) versus hydrochlorothiazide combination (-29.5 mm Hg) (mean difference, -5.6 mm Hg; 95% confidence interval, -8.3 to -2.9; P <.001). The mean difference in 24-hour ambulatory systolic blood pressure at week 6 was -5.8 mm Hg (95% confidence interval, -8.4 to -3.2; P <.001), favoring the azilsartan medoxomil/chlorthalidone group. The percentage of participants achieving target clinic blood pressure at week 6 was greater for the chlorthalidone versus hydrochlorothiazide combination (64.1% vs 45.9%, P <.001). Drug discontinuations due to adverse events were not statistically significantly different between groups (9.3% vs 7.3%, P = .38), and hypokalemia was uncommon in both groups.
Chlorthalidone combined with azilsartan medoxomil provides better blood pressure reduction and a higher likelihood of achieving blood pressure control than hydrochlorothiazide combined with azilsartan medoxomil. This benefit occurred without a difference in safety measurements.
氯噻酮已被证明能有效降低心血管发病率和死亡率，但在实践中使用频率却很低。本研究对氯噻酮与氢氯噻嗪进行了直接比较，两种药物均与血管紧张素受体阻断剂奥美沙坦酯联合使用，以比较降压效果和降压控制率。
这是一项随机、双盲、滴定至目标血压的临床试验，比较奥美沙坦酯与氯噻酮单一片剂联合用药与奥美沙坦酯与氢氯噻嗪联合用药在 2 级原发性高血压患者中的疗效。在单独使用奥美沙坦酯 40 mg 治疗 2 周后，所有患者还接受了 12.5 mg 的利尿剂治疗 4 周（直至第 6 周），如果未能达到目标血压，则将剂量滴定至 25 mg，再治疗 4 周（直至第 10 周）。主要终点为诊室收缩压的变化。目标血压定义为无糖尿病或慢性肾病的患者诊室血压<140/90 mmHg，或有糖尿病或慢性肾病的患者诊室血压<130/80 mmHg。
609 名参与者的平均年龄为 56.4 岁，基线时的平均诊室血压为 164.6/95.4 mmHg。第 6 周的主要终点分析显示，氯噻酮组（-35.1 mmHg）的诊室收缩压降低幅度大于氢氯噻嗪组（-29.5 mmHg）（平均差异，-5.6 mmHg；95%置信区间，-8.3 至-2.9；P<.001）。第 6 周 24 小时动态收缩压的平均差异为-5.8 mmHg（95%置信区间，-8.4 至-3.2；P<.001），氯噻酮组更优。第 6 周时，达到目标诊室血压的参与者比例氯噻酮组高于氢氯噻嗪组（64.1%比 45.9%，P<.001）。两组因不良反应停药的比例无统计学差异（9.3%比 7.3%，P=.38），且两组均少见低钾血症。
氯噻酮联合奥美沙坦酯可提供更好的降压效果，且更有可能达到降压控制目标，优于氢氯噻嗪联合奥美沙坦酯。这种获益并未带来安全性差异。
