CURRENT blood pressure (BP) management guidelines have so far only focused on BP targets based on measurements at a single time point, without consideration of the proportion of time that people are at target BP. But a growing evidence base suggests time-at-target is an accurate indicator of blood pressure, and the time is coming when clinicians will have the tools to use it with patients.
This focus on cross-sectional measurements has extended to clinical practice. On occasion, an implicit assumption is made that once target BP is first achieved, then future measurements will continue to remain at optimal target.
However BP is highly variable. Single BP measures taken even a few days or weeks apart are poorly reliable as they vary considerably by time of day and season. Many people with a measure below target BP could have many or even most future readings above target.
There is clear evidence that cumulative exposure to high BP is more closely related to organ damage, acute myocardial infarction and stroke than one-off BP readings. An analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA) study suggested that a high cumulative systolic BP was associated with increased left ventricular mass. Higher cumulative exposure to BP over 25 years from young adulthood to middle age has also been associated with increased risk of new onset left ventricular systolic and diastolic dysfunction and higher albuminuria.
New ways to assess BP are therefore needed apart from solely focusing on measures taken at single time points. Time-at-target is the percentage of time spent at the desired BP, and is a novel outcome to assess longitudinal BP control.
The TRIUMPH (TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension) trial was a randomised controlled open-label trial conducted by the George Institute for Global Health in urban hospital clinics in Sri Lanka.
The trial compared a once-daily fixed-dose triple combination BP lowering polypill (telmisartan 20 mg, amlodipine 2.5 mg, and chlorthalidone 12.5 mg [triple pill]) (n = 349) with usual care (n = 351). Adults were elgible if they had high BP (defined as BP > 140 mmHg and/or diastolic BP > 90 mmHg; or in patients with diabetes or chronic kidney disease: > 130 mmHg and/or > 80 mmHg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy. There were a total of 700 randomised patients (age, 56 ± 11 years; 58% women) recruited. For each individual, time at target was calculated as the percentage of time at target systolic and diastolic BP over the follow-up period as calculated by the extrapolation method used by Chung and colleagues using the BP readings at the different study time points. The number of days at target BP for systolic and diastolic readings were subsequently averaged. The proportion of time at target was calculated by dividing the number of days at target by the follow-up period in days, and then multiplying by 100 to achieve the percentage.
As shown in my recent co-authored research, patients who were taking the triple pill achieved a higher time at target compared with usual care over 24 weeks (64% v 43%; risk difference, 21%; 95%CI, 16–26%; P < 0.001). Almost twice as many patients on the triple pill spent the majority of follow-up time at target (64% v 37%; P < 0.001). The triple pill improved BP across subgroups, including age, sex, and comorbid conditions. The effect of the triple pill was also seen early, with most people who received the intervention spending the majority of time at target by 12 weeks. People on the triple pill achieved a consistently higher time at target BP at all follow-up periods compared with usual care (all P < 0.001).
Time at target is a new longitudinal measurement of BP control, which can improve upon current cross-sectional measures by being more reliable and consistent, and less susceptible to variability. This new outcome was able to detect treatment effects larger than those suggested by the cross-sectional primary outcome at 24 weeks used in the main trial, as time at target captured the benefits of both reduced time to BP control and more sustained BP control with low dose triple therapy.
Newer BP devices, including home BP and cuffless machines, will increasingly facilitate the capture of longitudinal control. Time at target not only provides assessment of time spent at target BP, it appears to provide superior prediction of cardiovascular outcomes, including risk of heart attacks and strokes, than cross-sectional BP values (here and here). A large cohort study of greater than 150 000 participants with newly diagnosed high BP found that a higher time at target was directly associated with a reduction in cardiovascular events. Another study similarly showed that improved time in even target systolic BP alone was associated with reduced cardiovascular events.
Time at target BP measurements currently remain a research tool as the measurements integrate systolic and diastolic BP, multiple time points and BP targets. Integration into clinical practice will require further validation of this new outcome, as well as incorporation into an easy to use application. Nevertheless, this new outcome highlights to clinicians the importance of taking a more holistic and longitudinal approach to BP rather than focusing on one-off measures.
The other key finding in our study was that the use of single pill combinations that combined low doses of BP lowering therapy (also known as “polypills”) was the key determinant of patients spending the majority of time at target BP. The clinical strategy of using single pill combination antihypertensive therapy at the outset can thus facilitate more rapid and effective BP control compared with gradual, multistep titration pathways.
Among patients with mild-to-moderate hypertension, treatment with a triple pill containing low doses of three BP-lowering medications led to an increased time at target compared with usual care. Greater assessment of longitudinal BP control is needed in clinical practice. For specific patient groups, clinicians could consider using low dose combination BP-lowering therapy, which has been shown to effectively achieve sustained BP control.
Dr Sonali Gnanenthiran is a cardiologist at the George Institute for Global Health, University of New South Wales; and the cardiology department at Concord Repatriation General Hospital in Sydney.
The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.
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