Garrison Scott R, Youngson Erik R E, Perry Danielle A, Campbell Farah N, Korownyk Christina S, Green Lee A, Kolber Michael R, Kirkwood Jessica E M, Allan G Michael, Kraut Roni Y, McAlister Finlay A, Hill Michael D, Bakal Jeffrey A
Pragmatic Trials Collaborative, University of Alberta, Edmonton, Alberta, Canada.
Department of Family Medicine, University of Alberta, Edmonton, Alberta, Canada.
JAMA Netw Open. 2025 May 1;8(5):e2513812. doi: 10.1001/jamanetworkopen.2025.13812.
The effect of antihypertensive administration time on major adverse cardiovascular events is unclear, and has never been studied in frail older adults, for whom risks and benefits may differ from the general population.
To determine, in frail seniors, the effect of bedtime vs morning administration of antihypertensive medications on major cardiovascular events and death, as well as on potentially ischemic or hypotensive adverse events.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, pragmatic randomized clinical trial recruited from 13 continuing care facilities in Canada (17 wards; 14 long-term care and 3 supportive-living wards) from May 25, 2020, to September 18, 2023, with follow-up until February 29, 2024. Residents with hypertension and at least 1 once-daily antihypertensive medication were included. Data analysis was from March to August 2024.
Patients were randomized 1:1 to taking all once-daily antihypertensive medications either at bedtime (intervention) or per usual care control (largely morning use).
The composite primary outcome was first occurrence of all-cause death or either hospitalization or emergency department (ED) visit for stroke, acute coronary syndrome, or heart failure. All-cause unplanned hospitalization or ED visits, falls and fractures, decubitus ulcers, and worsening cognition or behavioral problems were also assessed.
A total of 776 older adults (median [IQR] age, 88 [81-92] years; 562 female [72.4%]; 664 [85.6%] with some degree of dementia; 367 [47.3%] with diabetes; 307 [39.6%] with coronary artery disease) were randomized to bedtime (394 participants) vs usual care (382 participants) administration and were followed-up for a median (IQR) of 415 (251-735) days. Of 320 primary outcome events, 293 (91.6%) were deaths; there was no difference in primary outcomes for bedtime vs usual care in a modified intention-to-treat analysis (29.4 vs 31.5 events per 100 patient-years; adjusted hazard ratio [aHR], 0.88; 95% CI, 0.71-1.11; P = .28). Other outcomes were similarly no different between groups, excepting all-cause unplanned hospitalization and ED visits, which favored bedtime (22.6 vs 30.0 events per 100 patient-years; aHR, 0.74; 95% CI, 0.57-0.96; P = .02).
In this randomized clinical trial of antihypertensive medication timing, switching antihypertensives to bedtime failed to reduce a composite of death or major cardiovascular events that were primarily all-cause death, and had no effect on potentially ischemic and hypotensive adverse events, suggesting that in a population of frail older adults, administration time had little or no influence on the benefits and risks of antihypertensive medication.
ClinicalTrials.gov Identifier: NCT04054648.
抗高血压药物给药时间对主要不良心血管事件的影响尚不清楚，且从未在体弱的老年人中进行过研究，这类人群的风险和获益可能与普通人群不同。
在体弱的老年人中，确定睡前服用与早晨服用抗高血压药物对主要心血管事件和死亡的影响，以及对潜在的缺血性或低血压不良事件的影响。
设计、地点和参与者：这项多中心、开放标签、实用性随机临床试验于2020年5月25日至2023年9月18日从加拿大13个持续护理机构（17个病房；14个长期护理病房和3个支持性生活病房）招募，随访至2024年2月29日。纳入患有高血压且至少服用一种每日一次抗高血压药物的居民。数据分析时间为2024年3月至8月。
患者按1:1随机分组，将所有每日一次的抗高血压药物在睡前服用（干预组）或按常规护理（主要在早晨服用）。
复合主要结局是全因死亡或因中风、急性冠状动脉综合征或心力衰竭住院或急诊就诊的首次发生。还评估了全因非计划住院或急诊就诊、跌倒和骨折、压疮以及认知或行为问题恶化情况。
共有776名老年人（年龄中位数[四分位间距]为88[81 - 92]岁；562名女性[72.4%]；664名[85.6%]有某种程度的痴呆；367名[47.3%]患有糖尿病；307名[39.6%]患有冠状动脉疾病）被随机分配至睡前服用组（394名参与者）和常规护理组（382名参与者），并进行了中位数（四分位间距）为415（251 - 735）天的随访。在320例主要结局事件中，293例（91.6%）为死亡；在改良意向性分析中，睡前服用组与常规护理组的主要结局无差异（每100患者年29.4例 vs 31.5例事件；调整后风险比[aHR]，0.88；95%置信区间[CI]，0.71 - 1.11；P = 0.28）。除全因非计划住院和急诊就诊外，其他结局在两组间同样无差异，全因非计划住院和急诊就诊方面睡前服用组更优（每100患者年22.6例 vs 30.0例事件；aHR，0.74；95% CI，0.57 - 0.96；P = 0.02）。
在这项抗高血压药物给药时间的随机临床试验中，将抗高血压药物改为睡前服用未能降低主要为全因死亡的死亡或主要心血管事件的复合结局，且对潜在的缺血性和低血压不良事件无影响，这表明在体弱的老年人群中，给药时间对抗高血压药物的获益和风险几乎没有影响。
ClinicalTrials.gov标识符：NCT04054648。
