Results showed that on average, personalized treatment choice had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure.
New research provides evidence that widely used antihypertensive medications vary in effectiveness between patients, with the potential for greater reductions in blood pressure (BP) with personalized treatment.
In a new study of 280 Swedish adults with grade 1 hypertension (HTN), results showed that, on average, personalized treatment choice had the potential to provide an additional 4.4 mm Hg-lower systolic BP (SBP).
“While most hypertension guidelines advocate combination pharmacotherapy, many patients in routine care continue to be treated with monotherapy, with adverse effects and nonadherence being important clinical problems,” wrote authors of the Precision Hypertension Care (PHYSIC) randomized trial published in JAMA. “It is unknown whether the optimal choice of BP-lowering therapy varies from one person to another and whether individually targeted BP treatments can maximize clinical benefit.”
A team of researchers from Uppsala University in Sweden and the University of New South Wales in Australia aimed to examine and quantify the potential for targeting specific antihypertensive medications to specific persons to maximize BP effects.
A total of 280 adults with grade 1 HTN at low risk for cardiovascular events were scheduled for treatment in random order with agents from 4 different classes of BP-lowering drugs: lisinopril, candesartan, hydrochlorothiazide, and amlodipine. All participants received all 4 drugs and treatment periods were 7 to 9 weeks long. Following the initial 4 treatment periods, all participants repeated 2 of them, selected at random. In total there were 1468 treatment periods with a median length of 56 days.
The mean age of participants was 64 years and 54.3% were men. Participants had HTN for a mean of 3 years and approximately 62% had previously used BP-lowering monotherapy.
“Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment,” wrote investigators. The primary outcome was ambulatory daytime SBP, measured at the end of each treatment period.
Results showed that the BP response to different treatments varied considerably between participants (P<.001), specifically for lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Researchers excluded large differences for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine.
“These data showed that variation in SBP was large between treatments on average, between participants on average, within participants taking the same treatment, and between treatments in the same participant,” wrote first author Johan Sundström, MD, PhD, Department of Medical Sciences, Uppsala University, and colleagues.
Sundström and colleagues observed that personalized treatment using single-drug therapy would on average lead to a 4.4 mm Hg-lower SBP than a fixed choice.
“The potential for large BP-lowering gains from personalizing antihypertensive therapy highlights the need for a mechanism that can be used to identify which individuals will benefit most from which treatments,” wrote the research team.
Investigators noted that the study evaluated effects of monotherapy for practical reasons, but it is likely that there would also be benefits from personalization of the dual combination therapies recommended for initial treatment by most guidelines.
“The data from this study provide evidence of a substantial heterogeneity in BP response to drug therapy for hypertension,” concluded Sundström et al. “Given the size of the likely benefits, additional studies to confirm these findings, to test for the potential of personalization of combination antihypertensive therapy, and to identify mechanisms to enable the personalization of antihypertensive therapy in routine clinical practice should be a priority.”
Reference: Sundström J, Lind L, Held C, et al. Heterogeneity in blood pressure response to 4 antihypertensive drugs: A randomized clinical trial. JAMA. 2023;329:1160-1169.