Nighttime BP, rather than day-time BP, is regarded as a significant risk factor for cardiovascular morbidity and mortality. For this reason, it has been advocated that antihypertensive drugs be administered in the evening to control the nocturnal surge in BP and reduce the risk of adverse cardiovascular events. There is evidence to support this premise such as from the Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares (MAPEC) study¹ and more recently the Hygia Chronotherapy trial.²

The results of the large prospective TIME (Treatment In the Morning versus Evening) study, however, contradict these observations. The study found that time of taking the antihypertensive medication does not affect the cardioprotective effect of the drug.^3-5 No significant between-group differences were noted for MI, stroke or CV death occurrence. These findings were presented at the European Society of Cardiology (ESC) Congress 2022 in Barcelona, which concludes today.

The TIME study, led by the University of Dundee, followed 21,104 hypertensive patients, aged 65 years (average), for a median follow-up period of 5.2 years. The study population had a male preponderance (58%) and 98% were white. Of these, 10,503 participants were randomized to receive the antihypertensive medication in the evening (n = 10,503), while 10,601 were randomized to morning dosing of the medication. During follow-up, the hospitalizations and deaths were determined through medical records of the patients linked to national databases and via emails. There were no in-person visits. The objective of the study was to examine if evening dosing of the antihypertensive medication was more beneficial in improving cardiovascular outcomes compared to the morning dosing.

The primary composite endpoint of hospitalization for nonfatal myocardial infarction or nonfatal stroke, or vascular death occurred in 362 (3.4%) subjects in the evening dosing group (0.69 events per 100 patient years) compared to 390 (3.7%) participants in the morning dosing group (0.72 events per 100 patient years) with a hazard ratio of 0.95. No variation in results was observed in pre-specified subgroup analyses.

Based on these findings, the study concluded that the occurrence of cardiovascular events was comparable irrespective of the time of administration of the antihypertensive drug. One was not superior to the other. Therefore, according to this study, the best time for the patients to take the regular antihypertensive medication is as per their convenience, either in the morning or evening, and they should strictly adhere to it.

References

1. Hermida RC, Ayala DE, Mojón A et al.. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int 2010;27:1629–51) and more recently the Hygia Chronotherapy trial.
2. Hermida RC, et al; Hygia Project Investigators. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. Eur Heart J. 2020 Dec 21;41(48):4565-4576. doi: 10.1093/eurheartj/ehz754
3. Evening dosing of blood pressure medication not better than morning dosing. European Society of Cardiology Press release, August 26, 2022. Available at: https://www.escardio.org/The-ESC/Press-Office/Press-releases/Evening-dosing-of-blood-pressure-medication-not-better-than-morning-dosing.
4. University of Dundee Press Release, August 26, 2020. Available at: https://www.dundee.ac.uk/stories/evening-dosing-blood-pressure-medication-not-better-morning-dosing-according-study.
5. Rorie DA, et al. Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study. BMJ Open. 2016 Feb 9;6(2):e010313. doi: 10.1136/bmjopen-2015-010313.