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Taking antihypertensives at bedtime nearly halves cardiovascular deaths when compared with morning dosing, study finds

BMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l6173 (Published 23 October 2019) Cite this as: BMJ 2019;367:l6173

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Safety of Nighttime Dosing of Antihypertensives in Ophthalmology

Recent findings from the Hygia chronotherapy trial, published in the European Heart Journal and reported in the BMJ, have found the risk of cardiovascular death was more than halved in patients who took their antihypertensives at bed time compared with upon awakening intake [1,2]. Such strikingly result for a simple intervention did not carry treatment-time differences in the prevalence of patients reporting adverse effects at any visit during follow-up (6.7 vs. 6.0% for the awakening and bedtime-treatment regimen, respectively; P = 0.061). [1]

There is a growing evidence that low nighttime blood pressure could adversely affect glaucoma progression and increase the risk of ocular vascular disorders such as ischemic optic neuropathy [3,4]. It has also been hypothesized that antihypertensive medications administered at night may contribute to nocturnal hypotension [5]. Evidence from a small controlled trial (n=89) found that nocturnal compared with morning dosing of antihypertensive drugs was associated with worsening of glaucoma progression in patients with open-angle glaucoma [6]. Although there is a lack of clear evidence, morning administration of antihypertensive therapy may be preferred by ophthalmologists for certain vulnerable patients.

The Hygia chronotherapy trial did not exclude patients with history of ischemic optic neuropathy or glaucoma but it is unknown if ocular ischemic events were reported. Since many patients with glaucoma or ocular vascular disorders could suffer from arterial hypertension future generalization of the results should consider the benefit to risk ratio for vulnerable populations. Further trials to replicate this promising intervention should take into account potential ocular ischemic adverse events.

1. Hermida RC, Crespo JJ, Dominguez-Sardina M, etal . Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. Eur Heart J 2019. 10.1093/eurheartj/ehz754.
2. Mayor S. Taking antihypertensives at bedtime nearly halves cardiovascular deaths when compared with morning dosing, study finds. BMJ 2019;367:l6173.10.1136/bmj.l6173 31645337
3. Hayreh SS, Zimmerman MB, Podhajsky P, Alward WL. Nocturnal arterial hypotension and its role in optic nerve head and ocular ischemic disorders. Am J Ophthalmol. 1994;117(5):603–624. doi:10.1016/s0002-9394(14)70067-4
4. Charlson ME, de Moraes CG, Link A, et al. Nocturnal systemic hypotension increases the risk of glaucoma progression. Ophthalmology. 2014;121(10):2004–2012. doi:10.1016/j.ophtha.2014.04.016
5. Hayreh SS. Ischemic optic neuropathy. Prog Retin Eye Res. 2009;28(1):34–62. doi:10.1016/j.preteyeres.2008.11.002
6. Krasińska B, Karolczak-Kulesza M, Krasiński Z, et al. Effects of the time of antihypertensive drugs administration on the stage of primary open-angle glaucoma in patients with arterial hypertension. Blood Press. 2012;21(4):240–248. doi:10.3109/08037051.2012.666423

Competing interests: No competing interests

04 December 2019
Diego Macias Saint-Gerons
Postdoctoral researcher
Rafael Tabarés-Seisdedos
Department of Medicine, University of Valencia; INCLIVA Health Research Institute and CIBERSAM, Valencia, Spain
University of Valencia. Faculty of Medicine. Avenida Blasco Ibañez 15, 46010 Valencia