Weekly Journal Scan: BedMed cannot overcome the uncertainties on the effects of night-time antihypertensive therapy on cardiovascular outcomes

This comment refers to ‘Antihypertensive Medication Timing and Cardiovascular Events and Death. The BedMed Randomized Clinical Trial’ which was published in JAMA, https://doi.org/10.1001/jama.2025.4390. Nocturnal hypertension is thought to be associated with an increased risk of cardiovascular (CV) events, particularly in the vulnerable early morning period when BP increases rapidly, featuring the so-called ‘morning surge’.2 Elevated night-time BP levels seem to predict development of atherosclerotic CV disease, stroke, coronary artery disease, and HF.3–6 These observations have generated the hypothesis that the administration of antihypertensive treatment in the evening might improve CV outcomes through a more effective control of nocturnal hypertension and an improvement of the non-dipping pattern in ambulatory BP measurements (ABPM).2 This issue, however, remains largely controversial in view of the conflicting results reported by different studies. The MAPEC7 and the Hygia Chronotherapy Trial,8 conducted by the same investigators, which included 2156 and 19 084 hypertensive patients, respectively, showed that the routine administration of BP-lowering medications at bedtime, vs upon waking in the morning, produced remarkable (61% and 45%, respectively) reductions in the primary composite outcome of CV death, myocardial infarction (MI), coronary revascularization, stroke, or HF. It needs to be mentioned, however, that the Hygia Trial8 raised a number of serious concerns in the scientific community, due to the lack or insufficient information about fundamental data such as randomization implementation and allocation concealment, study protocol discontinuation, loss to follow-up, withdrawal from the study, medication adherence, and adverse effects.9