Is Taking Blood Pressure Medications at Night Really Better?

Christopher Labos, MD, CM, MSc


February 22, 2021

One of the ways to diagnose high blood pressure is with a 24-hour blood pressure monitor.

In healthy people, nocturnal blood pressure dips by about 15% compared with daytime values.

Patients who don't have this blood pressure drop at night, often called non-dippers, are at increased risk for cardiovascular mortality, heart failure, and stroke.

This has led many researchers to consider the issue of chronotherapy — the idea that when you take a pill is as important as or possibly more important than which pill you take.

Most patients take their blood pressure medications in the morning. But blood pressure is supposed to decrease at night, and switching some blood pressure medication to bedtime rather than morning makes intuitive sense.

The Hygia Chronotherapy trial reported very large decreases in stroke, MI, and death with nighttime dosing of antihypertensives.

The results got a lot of media attention.

But commentators quickly pointed out problems with this study.

First, the magnitude of the benefit was extremely large for a very small change in blood pressure.

Even nighttime blood pressure measurements showed only small differences between both groups.

Meta-regression studies have suggested that even with a 10-point reduction in blood pressure, one should expect around 20% relative risk reduction in cardiovascular disease, stroke, and all-cause mortality.

But the Hygia trial suggested that cardiovascular disease was nearly cut in half for a much smaller decrease in BP.

Second, switching blood pressure medication from morning to nighttime administration reduced not just CVD death but also total death, ie, all-cause mortality.

Why the timing of blood pressure medications should affect non-cardiovascular mortality to such a large degree is unclear — and somewhat implausible.

Finally, important questions about medical therapy really need to be decided by well-conducted randomized trials. But critics have questioned whether the Hygia Chronotherapy trial was actually randomized.

They point out that the word "randomized" was used only three times in the entire manuscript: once to define the acronym PROBE and twice to refer to a previous study on the same subject by the same authors.

These critiques and subsequent inquiries led the editors of the European Heart Journal to publish an "expression of concern" about the study, and the issue seems to be under investigation.

For now, it's not clear whether the timing of blood pressure medication really affects clinical endpoints to any significant degree.

In studies such as HOPE and EUROPA, in which medications were given at night, researchers did observe a reduction in cardiovascular events, but they were testing a medication vs placebo, not evening vs morning doses.

In the CONVINCE trial, nighttime verapamil, a calcium channel blocker, did not improve outcomes compared with morning doses of hydrochlorothiazide or atenolol. But again, researchers were not comparing evening vs daytime doses of the same medication.

For now, there is insufficient evidence to be certain that nighttime dosing of medication has much benefit.

But given that 1 in 5 Americans with high blood pressure is unaware that they have it and is not receiving any treatment for this very modifiable risk factor, chronotherapy might be less important than whether patients get any therapy at all.

Christopher Labos is a cardiologist with a degree in epidemiology. He spends most of his time doing things that he doesn't get paid for, like research, teaching, podcasting, and writing for the newspaper. Occasionally he finds time to practice as a cardiologist so that he can pay his rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn't know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal. To date, no one has recognized him on the street or asked for his autograph.

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