This article was originally posted in the Montreal Gazette.
For a while now there has been an ongoing debate about the issue of chronotherapy, which is the idea that what time of day you take your medications is significant. The idea has been particularly important in cardiology since the publication of the Hygia Chronotherapy Trial in late 2020. It found that giving patients their blood pressure medication at night rather than in the morning resulted in very large reductions in cardiovascular events and all-cause mortality. But the TIME trial, which was just presented at the European Society of Cardiology, showed no benefit when the same thing was tried.
Reconciling these types of contradictions is often difficult in medicine and conflicting results are more often the rule than the exception. But when it comes to blood pressure, some perspective is in order. We are much better at treating blood pressure today than we were 50 years ago. The medications are more effective, they last longer, and have fewer side effects. We are also more aggressive at treating high blood pressure. When U.S. president Franklin Delano Roosevelt died in office, his systolic blood pressure was over 200 and his physician’s advice boiled down to the suggestion that he should try taking it easy. A systolic blood pressure of 180 used to be considered “mild” hypertension and there was genuine debate about whether it was even worth treating. Now such numbers would drive people into a panic, and we spend most of our time optimizing people’s blood pressure to near-normal levels and debating among ourselves whether we should be targeting a blood pressure of 120 or 130.
Suffice it to say, blood pressure as a cardiovascular risk factor has less impact on society than it used to because we are simply better at treating it. However, improvement is always possible and the suggestion that blood pressure medication should be taken at night has some theoretical underpinnings. Blood pressure normally dips at night, and so taking your medication before bed would seem to make sense, to replicate that dip. The Hygia Chronotherapy Trial was designed to test this hypothesis. The results were a truly staggering reduction in both cardiovascular and non-cardiovascular mortality. Why switching blood pressure medication from morning to nighttime should have such a profound effect on non-cardiovascular mortality was slightly suspicious and many questioned the results. Two other studies, TIME and BedMed were designed to test the hypothesis and validate these findings, with the TIME trial having been completed first and presented at the recent conference.
It might seem wasteful to do the same study over again in a different country with a different group of patients. But replication is a key tool in research to ensure the validity of results. When independent groups of researchers can come to the same conclusion using different patient populations, then you can be more confident that the findings are actually true and not a spurious result. That is why the TIME trial was so important. It could have bolstered the somewhat controversial results of Hygia and silenced much of the criticism surrounding the trial. It didn’t, and that is equally important.
There is no doubt some people, for reasons of convenience or habit, prefer to take their medications at night. Side effects may also be more tolerable in the evening. Leg swelling will be less obvious when patients are lying in bed. Lightheadedness is less of an issue when you’re asleep. Only diuretics pose an obvious problem when taken just before bed, for self-evident reasons. But even with respect to side effects, the TIME trial showed no difference in major adverse effects between morning and nighttime administration of medication. Its conclusion was not that taking your pills in the morning is better. Its conclusion was that it didn’t matter.