In the European Society of Cardiology (ESC) Congress 2022, Professor Tom MacDonald from the University of Dundee, the United Kingdom, discussed his group’s findings on the differences between evening and morning dosing of antihypertensives with respect to cardiovascular (CV) outcomes.¹

A person’s blood pressure (BP) is heavily affected by one’s circadian rhythm.¹ The BP of a healthy individual naturally rises in the morning and dips at night.¹ However, in a group of patients called the “non-dippers”, their nighttime BP, which is a good predictor of bad outcomes, does not drop at night.¹ It suggested that taking antihypertensives in the evening could improve outcomes for this group of patients.¹

Previous trials have revealed findings supporting the above idea.1 Though with limited power, further studies were required to substantiate the hypothesis that nocturnal dosing of antihypertensives leads to more favorable CV outcomes compared with the traditional diurnal dosing.¹

The Treatment In the Morning versus Evening (TIME) study was a prospective, randomized, open-label, blinded endpoint study conducted over the internet to investigate the benefits of evening dosing of antihypertensives compared with morning dosing with respect to CV outcomes.¹

Self-enrolled on the study’s website, adult patients who were prescribed at least 1 antihypertensive drug taken once per day were randomized 1:1 to either take their antihypertensive medication in the morning (6:00-10:00) or in the evening (20:00-00:00).¹ Follow-up was performed via the online study portal and by email.¹ The primary endpoint was the composite of the first occurrence of hospitalized myocardial infarction (MI), hospitalized stroke or CV death.1 The secondary endpoints included hospitalization for non-fatal stroke, non-fatal MI, CV death, all-cause mortality and hospitalization or death from congestive heart failure (CHF).¹

The baseline characteristics were consistent across both groups.¹ Among the 21,104 patients enrolled, the average age was 65.1 years, with a mean body mass index (BMI) of 28.4.¹ Among the patients, 57.5% were male; 4.2% were smokers; 13.8% had diabetes; and 13.0% had prior CV diseases.¹ The mean BP at the time of entry was 135/79mmHg in both groups.¹ Comparing the rates of the primary endpoint in the evening dosing group with the morning dosing group, a result of HR=0.95; 95% CI: 0.83-1.10; p=0.53 was shown.¹ Besides, comparisons of the secondary endpoints indicated the following results: For non-fatal stroke, HR=0.93; 95% CI: 0.73-1.18; p=0.54; for non-fatal-MI, HR=0.92; 95% CI: 0.73-1.16; p=0.48; for CV death, HR=1.1; 95% CI: 0.84-1.43; p=0.49; for all-cause mortality, HR=1.04; 95% CI: 0.91-1.18; p=0.59; for CHF hospitalization or death, HR=0.79; 95% CI: 0.59-1.07; p=0.12.1 In addition, the rates of adverse events (AEs) were consistent across both groups.1 About 21.1% of the evening dosing group reported falls compared with 22.2% of the morning dosing group (p=0.05).¹ Non-hospitalized fractures occurred in 6.0% of patients in both groups, and hospitalized fractures occurred in 0.8% of patients in both groups (p=0.95).¹

In summary, the TIME study demonstrated all HRs close to 1 for the primary and secondary endpoints, and showed no safety concerns with regards to falls or fractures with nocturnal dosing.¹ These findings suggested neither beneficial nor harmful effects to taking antihypertensives in the evening with respect to CV outcomes.¹ Patients, therefore, are advised to take their medication at a time that is most convenient to them.¹