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Antihypertensives: Evening vs Morning Doses

| Photo: GETTY IMAGES

By Holadoctor



There has been a longstanding discussion about the best time of day to take medication to control hypertension. The Treatment in Morning versus Evening (TIME) study aimed to research whether evening dosing of usual antihypertensive medication improved major cardiovascular outcomes compared to morning dosing in patients with hypertension.

The prospective, pragmatic, decentralized study worked with parallel groups of individuals aged 18 and older from the United Kingdom. All participants were taking antihypertensive medication at the time of recruitment. They were randomly assigned to one of two groups: one group took the hypertension medications between 6 a.m. and 10 a.m. (10,601 people); and the other (10,053 people) between 8 pm. and 12 am.

The participant monitoring period was from December 2011 to June 2018, with the last follow-up appointment in March 2021. 57.5% were men and 42.5% were women. Ninety percent were white and the remaining percentage were black British, Caribbean, and African. 

Evidence from the TIME trial, funded by the British Heart Foundation, suggests that dosing time should not be an important consideration when advising most patients about controlling their blood pressure. Rather, physicians should focus on selecting appropriate medications and supporting compliance with the agreed-upon treatment plans.

These findings are an important addition to the thus far limited and controversial randomized clinical trial evidence available comparing the effects of the dosing times of antihypertensive drugs with respect to cardiovascular outcomes. 

Hypertension, or high blood pressure, is a key risk factor for cardiovascular disease worldwide. Proper control of hypertension reduces the risk of stroke, ischemic heart disease, and cardiovascular death.

The World Health Organization (WHO) states that the number of people living with hypertension has doubled since 1990: it now totals 1.28 billion. Of these, over 700 million have uncontrolled high blood pressure.

In Latin America, the countries with the highest prevalence of hypertension are Paraguay (62% of men and 51% of women); the Dominican Republic (49% of women); and Argentina (54% of men). Cardiovascular disease is the leading cause of death in Latin America and the Caribbean.

In the United States, nearly half of adults (47% or 116 million) have hypertension, defined as systolic blood pressure of 130 mmHg or diastolic blood pressure greater than 80 mmHg. Only one in four people have their hypertension under control.

Before the TIME study results were presented, a 2022 review by the International Society of Hypertension identified eight studies examining the relationship between the time when antihypertensives are taken and health outcomes. All eight studies were determined to have a high risk of bias and only two were “rescued” for scientific discussion: the MAPEC study and Hygia Chronotherapy, two prospective, randomized, open, blinded endpoint studies conducted by a single research group in Spain. 

The 2010 MAPEC study, with 2,156 participants, reported a substantial reduction in major cardiovascular events (cardiovascular death, myocardial infarction, ischemic stroke, and hemorrhagic stroke) in the group taking the medication at bedtime compared to the morning treatment group. 

The 2020 Hygia Chronotherapy trial, with 19,084 participants, also reported a substantial reduction in cardiovascular events (cardiovascular death, myocardial infarction, coronary artery bypass, heart failure, and stroke) in the bedtime treatment group compared with the morning treatment group. 

However, the HARMONY study found no significant differences between morning and evening doses.

Although these studies were validated by the scientific community, experts say that an independent study like the TIME study was needed to add information to the discussion, based on the analysis of a massive amount of data.

The study notes that nocturnal hypertension is an important predictor of adverse outcomes in people with hypertension, which has led to the hypothesis that taking antihypertensive medications in the evening could improve cardiovascular outcomes. 

Amidst these discussions, this study had sufficient statistical power to determine that there was no benefit to evening dosing compared to morning dosing. “We found no advantage of evening versus morning dosing of antihypertensive medication with regard to major cardiovascular outcomes or mortality.”

This story was produced using content from the original study and from other medical research, as well as health and public health sources, highlighted in related links throughout the article.