Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida.
Division of Nephrology, University of Chicago, Illinois.
Am J Med. 2021 Jul;134(7):918-925.e2. doi: 10.1016/j.amjmed.2020.12.015. Epub 2021 Jan 9.
Chlorthalidone is recommended over hydrochlorothiazide (HCTZ) as the preferred thiazide, but the supporting evidence is not robust at routinely used doses, or in whites vs blacks, in whom differences in response to thiazides are well known. We compare the efficacy and safety of HCTZ and chlorthalidone as first-line therapies for white and black hypertensive patients.
We compared treatment-related outcomes between the HCTZ arm (12.5 mg for 2-3 weeks; 25 mg for additional 6 weeks) of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR, n = 376) and chlorthalidone arm (15 mg for 2 weeks; 25 mg for additional 6 weeks) of PEAR-2 (n = 326) clinical trials, in 17-65-year-old mild-moderate uncomplicated hypertensive whites and blacks.
Mean systolic/diastolic blood pressure (SBP/DBP) reduction with HCTZ vs chlorthalidone: 8 ± 8/4 ± 5 vs 12 ± 9/7 ± 5 mm Hg in whites (P < 10 SBP and DBP); 12 ± 10/7 ± 6 vs 15 ± 10/9 ± 6 in blacks (P = .008 SBP, P = .054 DBP). Treatment with HCTZ vs chlorthalidone in whites resulted in significantly fewer patients achieving target BP (<140/90 mm Hg) (44% vs 57%, P = .018) and clinical response rate (≥10 mm Hg DBP reduction); and significantly higher nonresponse rate (<6 mm Hg DBP reduction); but no significant differences in rates among blacks (eg, target-BP rate: 56% vs 63%, P = .31). HCTZ treatment led to significantly lower rates of hypokalemia and hyperuricemia in whites and blacks, vs chlorthalidone, and significantly lower odds of requiring potassium supplementation among blacks (odds ratio 0.16; 95% confidence interval, 0.07-0.37; P = 3.4e).
Compared with HCTZ, chlorthalidone showed greater blood pressure lowering and adverse metabolic effects in whites, but similar blood pressure lowering and greater adverse effects in blacks; suggesting that the recent guideline recommendations to choose chlorthalidone over HCTZ may not be warranted in blacks.
氯噻酮被推荐为首选噻嗪类药物，优于氢氯噻嗪（HCTZ），但在常规使用剂量下，或在对噻嗪类药物反应存在差异的白人和黑人中，其支持证据并不充分。我们比较了 HCTZ 和氯噻酮作为白人及黑人高血压患者一线治疗的疗效和安全性。
我们比较了 Pharmacogenomic Evaluation of Antihypertensive Responses（PEAR）试验中 HCTZ 组（12.5mg 治疗 2-3 周；25mg 再治疗 6 周，n=376）和氯噻酮组（15mg 治疗 2 周；25mg 再治疗 6 周，n=326）的治疗相关结局，该试验纳入了 17-65 岁轻中度原发性高血压白人和黑人患者。
与氯噻酮相比，HCTZ 降低收缩压/舒张压的平均值：白人患者为 8±8/4±5mmHg（P＜10mmHg 的收缩压和舒张压）；黑人患者为 12±10/7±6mmHg（P=0.008 收缩压，P=0.054 舒张压）。与氯噻酮相比，HCTZ 治疗白人患者达到目标血压（＜140/90mmHg）的患者比例显著更低（44%比 57%，P=0.018），达到临床反应率（舒张压降低≥10mmHg）的患者比例显著更低；而非反应率更高（舒张压降低＜6mmHg），但黑人患者之间无显著差异（例如，目标血压达标率：56%比 63%，P=0.31）。HCTZ 治疗白人及黑人患者的低钾血症和高尿酸血症发生率显著更低，而氯噻酮治疗的患者中需要补充钾的比例显著更高（黑人患者中比值比为 0.16；95%置信区间，0.07-0.37；P=3.4e）。
与 HCTZ 相比，氯噻酮在白人患者中显示出更大的降压效果和代谢不良影响，但在黑人患者中则表现出相似的降压效果和更大的不良影响，这表明最近的指南建议选择氯噻酮而不是 HCTZ 可能不适用于黑人。
