Ever wondered whether there’s an ideal time to take blood pressure medication? Spoiler alert: There isn’t. Learn more here – and find out why you’re reading this in English.
For the first time since the beginning of the pandemic, the European Society of Cardiology Congress takes place as an in-person event. With usually more than 30.000 participants during the pre-pandemic years, the ESC Congress ranks among the largest medical conferences worldwide. In Barcelona, four updated ESC Guidelines will be presented and 37 Hotline Sessions will keep cardiologists busy for five days.
Given that cardiology is at the heart of this event – pun intended –, loads of technical stuff can be expected. But, having said that: The clinical trial that opened this year’s conference was not technical at all. On the contrary, it covered a topic important to clinical cardiologists, primary care physicians and all other internal medicine specialists. Prof. Thomas MacDonald, University of Dundee, presented the results of the TIME trial, a pragmatic randomized controlled trial in hypertension with 21.104 participants and a median follow-up duration of 5,2 years.
The trial was conducted with one specific question in mind: Does it matter at what of time of day patients take their antihypertensive drugs? The answer is: No. Not at all.
The question is relevant because it has been known for some time that nocturnal blood pressure is a better predictor of cardiovascular outcomes – myocardial infarction and stroke – than daytime blood pressure. So, one could argue that it’s only fitting to take blood pressure medication, or at least some of it, in the evening rather than in the morning. The latter is what the majority of patients already do. A much-discussed clinical trial claiming to show an advantage of nocturnal dosing was the Hygia study. But it attracted strong criticism and never made its way into guidelines, let alone clinical routine. The main argument here is that nocturnal dosing might affect fall risk, for example when patients need to get up at night. Not much data available on that up until now, either.
For MacDonald, the TIME trial settles all disputes regarding nocturnal versus early morning dosing: “TIME was one of the largest cardiovascular studies ever conducted and provides a definitive answer on the question of whether blood pressure lowering medications should be taken in the morning or evening. The trial clearly found that heart attack, stroke and vascular death occurred to a similar degree regardless of the time of administration. Timing makes no difference to cardiovascular outcomes at all.”
Of the 21.104 patients, 10.503 were randomized to evening dosing and 10.601 to morning dosing. The average age of the patients was 65 years, 58 % were men. Diabetics were overrepresented, but in all other aspects, the population mirrored the typical hypertension trial populations. Some of the participants were in the study for more than nine years. All of that makes it sound like an enormously expensive trial, but this, said MacDonald, wasn’t the case. Participants for the trial were pragmatically recruited online and dosing time was not monitored externally. Information on the primary endpoint components – hospitalization for myocardial infraction or stroke and vascular death of all kind – was obtained by email, by record linkage to UK databases and by contacting family doctors and hospitals. “All in all, the cost for the TIME trial were less than one million pounds.”
What about the event rates? 3,4 % of patients in the evening dosing group and 3,7 % of patients in the morning dosing group experienced a primary endpoint event. This translates into 0,69 and 0,72 events per 100 patient years respectively, giving an unadjusted hazard ratio of 0,95, which was not statistically significant. The trialist also did not find any pre-specified subgroup in which patients would have benefitted from either morning or evening dosing. The TIME trial also did not find any sign of additional harm by evening dosing. There was no increase in falls, neither during the day nor at night in any dosing group, according to MacDonald: “We also didn’t see any differences in fractures or fractures hospitalizations. People with high blood pressure should take their regular antihypertensive medications at a time of day that is convenient for them and minimizes any undesirable effects”, MacDonald said during an ESC press conference.
Up until now, our DocCheck newsletter was published exclusively in German – this is about to change. Starting with the ESC 2022 conference, DocCheck News expands its news portfolio with an English newsletter and News Shot, our fresh English news channel. Both focus on medical topics of international relevance. We’ll cover clinical trials, medical guidelines and case reports, but also political, ethical and public health issues. Stay tuned!
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