Nocturnal blood pressure dips by about 15% compared with daytime values in healthy individuals. 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 medication 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 sense. In the Hygia Chronotherapy trial, they reported substantial decreases in stroke, MI, and death with nighttime dosing of antihypertensives. However, there were several problems with the study.

First, the magnitude of the benefit was extremely large for a minimal change in blood pressure. Even nighttime blood pressure measurements showed only minor 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 CVD death and total death, i.e., all-cause mortality. Why the timing of blood pressure medications should affect non-cardiovascular mortality to such a large degree is unclear. Essential questions about medical therapy need to be decided by well-conducted randomized trials.

For now, it’s not clear whether the timing of blood pressure medication affects clinical endpoints to any significant degree. European Heart Journal