四种降压药物血压反应的异质性：一项随机临床试验。
Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial.
机构信息
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
出版信息
JAMA. 2023 Apr 11;329(14):1160-1169. doi: 10.1001/jama.2023.3322.
IMPORTANCE
Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown.
OBJECTIVE
To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment.
INTERVENTIONS
Each participant was scheduled for treatment in random order with 4 different classes of blood pressure-lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes.
MAIN OUTCOMES AND MEASURES
Ambulatory daytime systolic blood pressure, measured at the end of each treatment period.
RESULTS
There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P < .001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure.
CONCLUSIONS AND RELEVANCE
These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02774460.
重要性
高血压是全球导致过早死亡的主要风险因素。有多种降压治疗方法可供选择，但通过针对药物类别的个性化靶向来最大化获益的潜力尚不清楚。
目的
研究并量化通过针对特定个体靶向特定药物来最大化血压效果的潜力。
设计、地点和参与者：在瑞典一家门诊研究诊所中，对心血管事件风险低的 1 级高血压男性和女性进行了一项随机、双盲、重复交叉试验。混合效应模型用于评估个体对一种治疗的反应优于另一种治疗的程度，并估计通过个性化治疗可实现的额外降压效果。
干预措施
每位参与者按随机顺序安排接受 4 种不同类别的降压药物（赖诺普利[血管紧张素转换酶抑制剂]、坎地沙坦[血管紧张素受体阻滞剂]、氢氯噻嗪[噻嗪类利尿剂]和氨氯地平[钙通道阻滞剂]）的治疗，重复治疗 2 种药物。
主要结果和测量指标
每个治疗期结束时测量的动态日间收缩压。
结果
在 280 名随机参与者中的 270 名参与者中，共记录了 1468 个完成的治疗期（中位数长度为 56 天）（54%为男性；平均年龄为 64 岁）。不同治疗方法对个体的血压反应差异很大（P < .001），特别是在赖诺普利与氢氯噻嗪、赖诺普利与氨氯地平、坎地沙坦与氢氯噻嗪和坎地沙坦与氨氯地平的选择上。赖诺普利与坎地沙坦和氢氯噻嗪与氨氯地平的选择则排除了较大差异。平均而言，个性化治疗有可能使收缩压再降低 4.4 毫米汞柱。
结论和相关性
这些数据揭示了高血压药物治疗的血压反应存在显著的异质性，这可能对个性化治疗具有重要意义。
试验注册
ClinicalTrials.gov 标识符：NCT02774460。
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