Taking prescribed blood pressure (BP) medication in the evening is no better or worse than taking it in the morning for the prevention of cardiovascular disease (CVD), according to data from the U.K.’s TIME trial. Findings from the study of more than 21,000 patients with high blood pressure followed for over 5 years were reported Friday at the European Society of Cardiology (ESC) Congress 2022 in Barcelona, Spain, where the study’s principal investigator Thomas MacDonald, BSC, MBCHB, MD, from the University of Dundee, Scotland, presented late-breaking findings from the trial. While nocturnal blood pressure is established as a better predictor of cardiovascular outcomes than daytime blood pressure, there has been mixed messaging on the best timing for antihypertensive drugs to be taken – with some suggesting that taking medication in the evening rather than in the morning reduced night-time blood pressure to a greater extent. Indeed, the team noted that the Hygia study has previously reported a protective effect of evening dosing on cardiovascular events, but added that the study has attracted significant criticism over both its methodology and the reliability of its findings. “TIME was one of the largest cardiovascular studies ever conducted and provides a definitive answer on the question of whether blood pressure lowering medications should be taken in the morning or evening,” said MacDonald. “The trial clearly found that heart attack, stroke and vascular death occurred to a similar degree regardless of the time of administration. People with high blood pressure should take their regular antihypertensive medications at a time of day that is convenient for them and minimizes any undesirable effects.” Study setup TIME was a large prospective, randomized trial set up to investigate whether evening dosing of antihypertensive medication improved major cardiovascular outcomes compared with morning dosing. MacDonald noted that the study used a large, decentralized cloud of patients treated in the U.K.’s National Health Service (NHS). Adults taking at least one antihypertensive medication and with a valid email address were recruited by advertising in the community, from primary and secondary care, and from databases of consented patients in the U.K. Patients signed up via the trial website, where their eligibility was confirmed before they were randomized 1:1 to take their usual antihypertensive medication in either the morning or the evening. In total, 21,104 patients were randomized to take BP medication in either the morning (n=10,601) or evening (n=10,503) for over 5 years, with a median follow-up duration of 5.2 years and the longest follow-up at 9.3 years. The average age of participants was 65 years, 58% were men and 98% were white. The composite primary endpoint was hospitalization for non-fatal myocardial infarction (MI) or non-fatal stroke or vascular death, in the intention-to-treat population. These outcomes were tracked by patient and clinician reports, NHS hospital databases and death records, said MacDonald. The lead researcher added that the study setup – using web sign-ups and a large, decentralized cloud system – “is the way research is going to go because you can do very large trials cost-effectively this way.” Key findings The team used an intention-to-treat analysis, reporting no significant differences in MI, stroke or vascular death between morning dosing (390 participants; 3.7% incidence) and evening dosing (362 participants; 3.4% incidence) over the follow-up period (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.83-1.10; p=0.53). Furthermore, MacDonald noted that when looking at secondary outcomes, they were “all much the same” with no significant differences seen between morning and evening dosing for non-fatal stroke (HR 0.93; 95% CI 0.73-1.18; p=0.54), non-fatal MI (HR 0.92; 95% CI 0.73-1.16; p=0.48), CV death (HR 1.1; 95% CI 0.84-1.43; p=0.49), all-cause mortality (HR 1.04; 95% CI 0.91-1.18; p=0.59), and congestive heart failure (CHF) hospitalization or death (HR 0.79; 95% CI 0.59-1.07; p=0.12). The results did not vary in pre-specified subgroup analyses, he added. “The key messages for this study are taking tablets for your high blood pressure in the evening wasn't different at all from taking them in the morning for preventing heart attack strokes and vascular deaths,” said MacDonald. “Our conclusion is that patients can take their tablets whenever it's convenient to them.” The TIME study was funded by the British Heart Foundation and supported by the British and Irish Hypertension Society and the National Institute for Health and Care Research in the U.K.