The findings of TIME trial presented at the European Society of Cardiology (ESC) Congress 2022 reported that individuals with hypertension who consumed antihypertensive drugs in the morning or the evening experienced identical risks of cardiovascular events over the subsequent five years. The findings of this pragmatic trial contradicted numerous earlier studies that suggested that evening dosage is better. According to this study, there is no significant difference between taking antihypertensive medicine in the morning and the evening in terms of preventing vascular deaths, heart attacks, and strokes.

The intention-to-treat population's hazard ratio for the key outcome, a composite of hospitalization for nonfatal myocardial infarction, vascular death, or nonfatal stroke was 0.95. Similar outcomes were observed across all secondary outcomes and subgroups, with a hazard ratio of about 1.  The study also illustrated that taking a dose in the evening had no negative effects on falls or other outcomes. If a patient gets up in the middle of the night to use the restroom, taking the drug at night can trigger nocturnal hypotension. This might elicit greater dizziness and falls.

During the day, more dizzy turns were reported. Both groups' rates of fractures and hospitalization for fractures were similar. Individuals can take their blood pressure medications whenever it is convenient for them. Usually, it is better to establish a schedule for taking tablets at the same time each day. It doesn't matter whether the medicine is consumed in the evening or morning. The investigation was justified by the fact that nocturnal blood pressure is the best indicator of unfavorable outcomes in individuals whose blood pressure does not decrease at night (non-dippers).

Moreover, earlier research has demonstrated that antihypertensive agents should be used in the evening rather than the afternoon to effectively decrease blood pressure at night.  The findings indicated that blood pressure is greater in the morning and reduced in the evening when the antihypertensive drug is taken in the morning. On the other hand, blood pressure is reduced in the morning and raised in the evening when taking an evening dose. One to two mmHg is not a significant change, and this didn't influence the results in any way. The ideal drug must successfully minimize blood pressure for the entire 24 hours.

In the TIME Study, 21,104 people with treated hypertension were randomly allocated to take their antihypertensive drug in the evening or morning. The baseline data indicated that volunteers had an average age of 65, 14% had diabetes, 4% smoked, 13% had a history of cardiovascular disorder,

and the mean blood pressure at trial entry was 135/79 mmHg. In this trial, volunteers were included from primary and secondary care online. Data on hospitalizations and mortality were procured from volunteers via email and record linking to national databases. Additional information was collected from family physicians and hospitals.

A blinded committee independently assessed the results. The volunteers were followed up for a median of 5.2 years. However, others were kept under observation for up to nine years. With an unadjusted hazard ratio (HR) of 0.95, the key outcome was experienced by 362 (3.4%) volunteers in evening-dosing group (0.69 events per 100 patient-years) and 390 (3.7%) volunteers in morning-dosing group (0.72 events per 100 patient-years). Observers' perspectives on how the TIME outcomes ought to be integrated into clinical practice were divided.

The TIME research raised a very significant question and the data are clearly provocative. The trial was completely neutral and all the events were adjudicated. Compliance was good enough at 60%. For the general population of hypertensive people, no discernible difference was noted in the morning vs evening dosing. A wide array of previous studies claimed that taking medication in the evening improved blood pressure at night and decreased cardiovascular events. The TIME study's finding that there was no difference in the incident rate is thus quite interesting. According to prior studies, several patient populations, including those with nocturnal hypertension, sleep apnea, and non-dippers, have benefited from nighttime dosage.

The Hygia Chronotherapy Trial, a prior high-profile trial that indicated a considerable protective impact of nocturnal dosage on cardiovascular events and received substantial media attention, was published in 2020. The TIME results are directly at odds with this study. Additionally, a systematic review from International Society of Hypertension (ISH) found "significant problems" in earlier studies of antihypertensive medication before sleep. The study points out that 3 ongoing, carefully planned, prospective, randomized controlled outcome trials are anticipated to yield high-quality information on the effectiveness and safety of evening or nighttime drug dosage in comparison to morning dose.

Preferred usage of bedtime drug doses of antihypertensive medicines should not be routinely advocated in clinical practice until relevant information is available. Utilizing commercially available, long-acting antihypertensive drugs as monotherapy or combos given in a single morning dose, complete 24-hour management of blood pressure should be the goal. Since the benefits of bedtime dosing were not verified, habitually recommending medicine dosage before sleep may be inappropriate in clinical practice. The TIME study did not reveal any harm with bedtime dosing.

In the vast majority of well-conducted outcome studies to direct hypertension management, all medications were provided in the morning. The TIME experiment was a significant and well-conducted study that offered much more dependable results than the Hygia study. Patients can choose when to take their prescriptions based on scientific considerations. However, it is firmly suggested to take antihypertensives in the morning. At bedtime, adhesion has been shown to be worse. But, if a patient has elevated nighttime blood pressure, doctors may still recommend bedtime dosing.

The results of the TIME trial do not agree with the reported results of numerous trials on the influence of timed hypertension treatment on blood pressure control and circadian pattern regulation,  cardiac pathology, and renal function. The design and execution of the TIME study do not meet the quality needs listed in guidelines by International Society for Chronobiology for conducting chronotherapy trials in hypertension. The TIME results are fairly obvious; taking blood pressure medication in the morning or evening does not make any difference on the difficult outcomes feared in people suffering from hypertension.

Although there were few variations in the blood pressure estimated in the morning or the evening, clinical events don't seem to be impacted by this. It might be challenging to take drugs consistently at the same time each day. This indicates that patients' lives may be a little bit easier because they can choose the best time for them to take their prescriptions. For people taking multiple medications, a potential substitute strategy is to take one medication in the evening and the other in the morning, thus offering better 24-hour coverage.