Response to Lowering Nighttime Blood Pressure with Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Pro Side of the Argument

Hermida et al make a good case about the importance of ambulatory blood pressure monitoring and nocturnal hypertension, with which we agree. Otherwise, in their defense of chronotherapy, they rely on their own duplicate publications of the same systematic review (PROSPERO registration CRD42020201220), which include a plurality of studies from their own group, and are limited by inclusion of cross-sectional, overlapping, and otherwise biased studies. Notably, this review was not conducted according to Cochrane methodology nor properly reported according to PRISMA guidance. Hermida et al continue their inconsistent criticism of other studies with discordant results, casting aspersions on sample size of properly conducted and clearly reported trials (HARMONY) and ongoing trials with rigorous protocols (BEDMED and TIME). They accept evening dosing (as opposed to bedtime) when the conclusions align with their own (e.g. Roush systematic review), but raise it as a weakness when they do not. More importantly, no further details or explanation are provided for the incredible benefit seen in Hygia for non-cardiovascular mortality, and the unprecedented lack of adverse effects. The investigation reported by European Heart Journal editors suggests that Hygia was a low cost trial embedded in routine care that lacked the robust measurement of adherence, adverse events, and event adjudication typically expected from clinical trials. This is the most plausible explanation for their findings, and the medical community should await the results of more rigorous ongoing clinical trials.