Timing of hypertension medication administration does not affect adverse CV outcomes

Blood pressure medications can be taken in the evening or in the morning because the time of administration does not affect cardiovascular outcomes

Blood pressure medications can be taken in the morning or in the evening, as the time of administration has no effect on adverse cardiovascular outcomes, according to the results of a randomized trial conducted by a team of British researchers.

Among cardiovascular disease risk factors, high blood pressure (BP) is associated with the strongest evidence of causation and preventing age-related increases in blood pressure would eliminate much of the population burden of CVD. related to BP. Blood pressure in normotensive people follows a diurnal rhythm, plunging at night followed by a rise in the morning. In addition, there is also a marked diurnal variation in the time of onset of cardiovascular events, with the peak observed in the early morning. An important question for patients, therefore, is when would be the best time to take their blood pressure medication to reduce the risk of an adverse cardiovascular event. In a 2010 randomized crossover trial, the authors reported that in hypertensive patients with controlled BP, the timing of antihypertensive medication administration (morning or evening) did not affect mean blood pressure levels over 24 hours or in clinic. Nevertheless, the MAPEC study found that administration at bedtime resulted in better blood pressure control and reduced risk of cardiovascular morbidity and mortality compared to administration in the morning. In 2022, an International Society of Hypertension position paper that was endorsed by the World Hypertension League and the European Hypertension Society, concluded that the preferred use of bedtime antihypertensive drug dosing should not be routinely recommended in clinical practice. Despite this, the Hygia Chronotherapy trial, which again assessed the relative benefits of night versus morning administration of a blood pressure medication, concluded that the former was more effective in controlling blood pressure and reduce cardiovascular events.

Although the Hygia trial had nearly 20,000 participants, concerns have been raised about its findings. In an attempt to settle the argument over the best time to administer blood pressure medication, the British team established the Treatment in Morning versus Evening (TIME) study. TIME was an open-label, blinded, endpoint-controlled superiority trial and participants were randomized 1:1 to receive morning (6 a.m. to 10 a.m.) or evening (8 p.m. to 12 p.m.) the dosage of their antihypertensives. The primary endpoint was a composite cardiovascular outcome of vascular death or hospitalization for nonfatal myocardial infarction or nonfatal stroke, while secondary endpoints were the individual components of the endpoint. main evaluation.

Hypertension Drug Dosage and Cardiovascular Outcomes

A total of 21,104 people with a mean age of 65.1 years (42.5% women) were enrolled and followed for a median of 5.2 years, of whom 10,503 were assigned to administer the evening. Mean systolic blood pressures were similar overall (135 mmHg in the evening group versus 134.8 in the morning group) as were diastolic pressures (79.1 versus 78.8 mmHg).

The primary outcome occurred in 3.4% of those assigned to the evening administration and 3.7% of the morning group and this difference was not significant (Hazard ratio, HR=0.95, CI to 95% 0.83 – 1.10, p=0.53). Similarly, there were no significant differences for any of the secondary endpoints.

The authors concluded that there was little difference in adverse cardiovascular outcomes when blood pressure medications were taken in the evening or in the morning.

Mackenzie IS et al. Cardiovascular outcomes in hypertensive adults with evening or morning administration of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded clinical trial. Lancet 2022

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