Hot Line - What did the Treatment in Morning versus Evening (TIME) study tell us?

Previous studies had suggested a large CV benefit of night-time versus morning blood pressure lowering medication.¹ However, the generalisability of these findings has been questioned² and the large pragmatic blinded-endpoint TIME study was conducted to provide robust evidence on the optimal timing of antihypertensive dosing.

As presented by Professor Thomas MacDonald (University of Dundee - Dundee, UK) in a Hot Line session yesterday, 21,104 adults taking at least one antihypertensive medication and with a valid email address were recruited to the TIME study by advertising in the community, from primary and secondary care, and from databases of consented patients in the UK. After their eligibility was confirmed, patients were randomised 1:1 to take their usual antihypertensive medication in the morning or the evening. Follow-up occurred via regular email follow-up and record-linkage to centralised databases of hospitalisations and deaths. The average age of participants was 65 years, 58% were men and 98% were white. The median follow-up duration was 5.2 years, but some were in the study for over 9 years.

There was no difference in the primary endpoint with evening versus morning dosing. The composite primary endpoint of hospitalisation for non-fatal myocardial infarction, non-fatal stroke or vascular death occurred in 3.4% of participants in the evening dosing group (0.69 events per 100 patient years) and 3.7% in the morning dosing group (0.72 events per 100 patient years), giving an unadjusted hazard ratio of 0.95 (95% CI 0.83 to 1.10; p=0.53). The results did not vary in prespecified subgroup analyses.

Prof. MacDonald summarises the trial and its findings by saying, “TIME was one of the largest CV 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. People with high blood pressure should take their regular antihypertensive medications at a time of day that is convenient for them and minimises any undesirable effects.”