近日，阿尔伯塔大学Michael Allan团队研究了抗高血压药物的用药时机与心血管事件和死亡的相关性。相关论文于2025年5月12日发表在《美国医学会杂志》上。

由于大型临床试验的结果并不一致，睡前而不是早上服用降压药物是否会降低心血管风险尚不清楚。人们还担心，睡前使用抗高血压药物可能会导致青光眼相关的视力丧失或其他低血压/缺血性不良反应。

为了确定睡前与早晨服用抗高血压药物对重大心血管事件和死亡的影响，研究组进行了一项多中心、开放标签、实用的随机临床试验，通过加拿大5个省的436名初级保健临床医生进行盲法终点评估和招募，邀请其社区居住的成年高血压患者每天至少服用1次抗高血压药物。参与者于2017年3月31日至2022年5月26日招募，最终随访时间为2023年12月22日。

将参与者以1:1的比例随机分配，在睡前服用所有每日一次的抗高血压药物（干预组；n = 1677）或在早晨服用（对照组；n = 1680）。主要结局是首次发生全因死亡或因中风、急性冠状动脉综合征或心力衰竭住院/急诊（ED）就诊的时间。还评估了全因意外住院/ED就诊以及视觉、认知和跌倒和/或骨折相关的安全性结局。

共有3357名成年人（56.4%为女性；中位年龄67岁；53.7%服用单一疗法）被随机分配，每个治疗组的中位随访时间为4.6年。睡前组的复合主要结局事件发生率为2.3/100患者-年，晨间组为2.4/100患者-年（调整后的风险比为0.96；95%CI为0.77-1.19；P = .70）。主要结局、全因住院/ED就诊和安全性结局的各个组成部分在各组之间没有差异。特别是，在跌倒或骨折、新的青光眼诊断或18个月的认知能力下降方面没有差异。

研究结果表明，在初级保健中患有高血压的成年人中，睡前服用抗高血压药物是安全的，但并没有降低心血管风险。抗高血压药物的给药时间不影响降压药物的风险和益处，而是应该以患者的偏好为指导。

附：英文原文

Title: Antihypertensive Medication Timing and Cardiovascular Events and Death: The BedMed Randomized Clinical Trial

Author: Scott R. Garrison, Jeffrey A. Bakal, Michael R. Kolber, Christina S. Korownyk, Lee A. Green, Jessica E. M. Kirkwood, Finlay A. McAlister, Raj S. Padwal, Richard Lewanczuk, Michael D. Hill, Alexander G. Singer, Alan Katz, Michael D. Kelmer, Armine Gayayan, Farah N. Campbell, Ana Vucenovic, Nathan R. Archibald, Jack M. S. Yeung, Erik R. E. Youngson, Kimberlyn McGrail, Braden G. O’Neill, Michelle Greiver, Donna P. Manca, Roni Y. Kraut, Ting Wang, Braden J. Manns, Dee A. Mangin, Cathy MacLean, James McCormack, Sabrina T. Wong, Colleen Norris, G. Michael Allan

Issue&Volume: 2025-05-12

Abstract:

Importance  Whether administration of blood pressure medications at bedtime instead of in the morning reduces cardiovascular risk is unknown, as findings from large clinical trials have not been consistent. There is also concern that bedtime antihypertensive use could induce glaucoma-related visual loss or other hypotensive/ischemic adverse effects.

Objective  To determine the effect of bedtime vs morning administration of antihypertensive medications on major cardiovascular events and death.

Design, Setting, and Participants  Multicenter, open-label, pragmatic randomized clinical trial with blinded end-point assessment and recruitment via 436 primary care clinicians across 5 Canadian provinces inviting their community-dwelling adult patients with hypertension taking at least 1 once-daily antihypertensive medication. Participants were recruited from March 31, 2017, to May 26, 2022, with final follow-up on December 22, 2023.

Interventions  Participants were randomized in a 1:1 ratio to using all once-daily antihypertensive medications either at bedtime (intervention group; n=1677) or in the morning (control group; n=1680).

Main Outcomes and Measures  The primary outcome was time to first occurrence of all-cause death or hospitalization/emergency department (ED) visit for stroke, acute coronary syndrome, or heart failure. All-cause unplanned hospitalizations/ED visits, and visual, cognitive, and fall- and/or fracture-related safety outcomes were also assessed.

Results  A total of 3357 adults (56.4% female; median age, 67 years; 53.7% taking monotherapy) were randomized and followed up for a median of 4.6 years in each treatment group. The composite primary outcome event occurred at a rate of 2.3 per 100 patient-years in the bedtime group and 2.4 per 100 patient-years in the morning group (adjusted hazard ratio, 0.96; 95% CI, 0.77-1.19; P=.70). Individual components of the primary outcome, all-cause hospitalizations/ED visits, and safety outcomes did not differ between groups. In particular, there was no difference in falls or fractures, new glaucoma diagnoses, or 18-month cognitive decline.

Conclusions and Relevance  Among adults with hypertension in primary care, bedtime administration of antihypertensive medications was safe but did not reduce cardiovascular risk. Antihypertensive medication administration time did not affect the risks and benefits of blood pressure–lowering medication and instead should be guided by patient preferences.

DOI: 10.1001/jama.2025.4390

Source: https://jamanetwork.com/journals/jama/fullarticle/2833860