Should We Be Using Time in Therapeutic Range as a Performance Measure for Hypertension Control?
Michael J. Bloch, MD
Associate Professor, University of Nevada School of Medicine
Medical Director, Renown Vascular Care, Renown Institute for Heart and Vascular Health
President, Blue Spruce Medical Consultants, PLLC
Bloch M. Should we be using time in therapeutic range as a performance measure for hypertension control? Consultant360. Published online May 12, 2021.
Like blood pressure (BP), serum glucose is a highly variable biological metric. Because of this limitation, in patients with diabetes we do not use fasting glucose as the primary measure to determine overall glycemic control. Instead we mainly rely on the level of glycosylated hemoglobin (HbA1c) for clinical decision-making and as a performance measure. Lacking such a biomarker in hypertension, we instead tend to use the most recent BP measurement, which may or may not be representative of a patient’s true overall BP control. If a patient’s most recent BP is higher than a specific threshold, guidelines suggest intensification of therapy largely independent of previous values. Similarly, if the most recent BP is not lower than a specific threshold, we usually consider a patient to have “uncontrolled” hypertension regardless of whether previous values were lower than that same threshold.
In the field of anticoagulation, for patients taking warfarin, rather than rely on the last international normalized ratio, we more frequently use a concept known as time in therapeutic range (TTR) as the performance measure for clinics and providers, and we will often base clinical decisions regarding dose, dietary recommendations, and potential need to change anticoagulants on an individual patient’s TTR.
Using an analogous approach, Fatani and colleagues undertook a retrospective analysis of the landmark Systolic Blood Pressure Intervention Trial (SPRINT) where they identified each patient’s TTR over the first 3 months of the trial.1 They then examined the relationship between TTR and subsequent cardiovascular (CV) events. Overall, the median TTR for systolic BP was 47% in the intensively treated group (goal systolic BP, < 120 mmHg) and 51% for the standard treatment group (goal systolic BP, < 140 mmHg). In COX proportional hazards regression models, each standard deviation increase in TTR was associated with a decreased risk of CV events, independent of mean systolic BP and BP variability.
These and similar data suggest that TTR may be a better marker of CV risk and, as such, a more useful clinical and performance measure than using the most recent BP measurement.2,3 Indeed, targeting a range of BP—say systolic BP of 120 to 129 mmHg—rather than using a hard threshold for intensification, makes intuitive sense and would perhaps defuse some of the controversy surrounding the more-aggressive BP goals recommended in many recent clinical practice guidelines. As Egan and colleagues have illustrated in elegant mathematical modeling of a number of observational studies, if we use the most recent systolic BP measurement as our goal, given the variability of BP, getting 88% of patients lower than the threshold of 130 mmHg would require 25% to 30% of patents to have a systolic BP of 110 to 119 mmHg and approximately 40% of patients at a systolic BP level lower than 110 mmHg.2 Clearly this would mean significant overtreatment in many individuals to get the majority of readings lower than this somewhat arbitrary threshold.
Further observational studies should be performed that compare TTR with other BP parameters like most recent BP measurement, not just in the office setting but also with home and ambulatory BP monitoring. Eventually, a prospective randomized clinical trial could be performed where patients or providers are randomly assigned to a strategy of using threshold BP or TTR to guide changes in therapy. Certainly, our current concept of goal or threshold BP measurements has been enshrined in clinical practice for decades and has been the framework for most of our major landmark clinical trials. But we should recognize the limitations of this strategy and be open to considering other ways of thinking about BP control in the future.
- Fatani N, Dixon DL, Van Tassell BW, Fanikos J, Buckley LF. Systolic blood pressure time in target range and cardiovascular outcomes in patients with hypertension. J Am Coll Cardiol. 2021;77(10):1290-1299. https://doi.org/10.1016/j.jacc.2021.01.014
- Egan BM, Kjeldsen SE, Grassi G, Esler M, Mancia G. The global burden of hypertension exceeds 1.4 billion people: Should a systolic blood pressure target below 130 become the universal standard? J Hypertens. 2019;37(6):1148-1153. https://doi.org/10.1097/hjh.0000000000002021
- Doumas M, Tsioufis C, Fletcher R, Amdur R, Faselis C, Papademetriou V. Time in therapeutic range, as a determinant of all-cause mortality in patients with hypertension. J Am Heart Assoc. 2017;6:e007131. https://doi.org/10.1161/jaha.117.007131