Blood Pressure Treatment Choice is Not One Size Fits All, Study Suggests

Johan Sundström, MD, PhD
Credit: Uppsala University

A new study from Uppsala University is providing evidence in support of a more focused, precision medicine approach to managing hypertension.

A study of 280 patients testing the heterogeneity of 4 antihypertensive medications, results of the study indicate heterogeneity exists in blood pressure response to drug therapy for hypertension. Investigators purport these results, which indicate personalized treatment choice could lead to a 4.4 mmHg lower systolic blood pressure than a fixed choice, underlines the importance of personalized medicine in cardiovascular care.

“The effect of a change of medication can be twice as great as the effect of doubling the dose of the patient’s current medication. It was clear in our study that certain patients achieved lower blood pressure from one drug than from another. This effect is large enough to be clinically relevant,” said lead investigator Johan Sundström, cardiologist and professor of epidemiology at Uppsala University.²

A major public health crisis with serious implications, the increased risk of cardiovascular events associated with uncontrolled hypertension poses a risk to millions in the US alone. In 2021, a systematic review and meta-analysisexamining prevalence of hypertension suggested rates had doubled globally between 1990 and 2019, despite advances in technology and care.³

In the current study, Sundström and a team of colleagues sought to estimate the potential magnitude of benefit seen with personalized drug therapy in hypertension. With this in mind, investigators designed their research endeavor as a randomized, double-blind, repeated crossover trial. Named the Precision Hypertension Care (PHYSIC) trial, the trial enrolled men and women with grade 1 hypertension considered to be at low risk of cardiovascular events from an outpatient research clinic in Sweden from February 20, 2017, through May 25, 2020.¹

Overall, 391 patients underwent screening for the study, with 280 patients undergoing randomization following a 2-week, placebo run-in. Those who underwent randomization were assigned to a sequence of 6 treatment periods administered in random order. Per trial protocol, every participant had 1 treatment period with 16 mg candesartan, 20 mg lisinopril, 10 mg amlodipine, and 25 mg hydrochlorothiazide. Investigators pointed out each treatment period was 7-9 weeks in duration, with a 1-week washout period with placebo between each treatment period. Investigators also noted every participant repeated 2 of the treatment periods selected at random.¹

The study cohort had a mean age of 64 years and 54.3% were men. This cohort had hypertension for a mean of 3 years, 62.1% had previously used antihypertensive monotherapy, and the mean office blood pressure after placebo run-in was 154/88 mmHg.¹

For the purpose of analysis, mixed-effects models were used to evaluate the extent to which individuals responded better to one treatment relative to another as well as to assess additional blood pressure lowering achievable by personalized treatment.¹

Overall, 1468 completed treatment periods, with a median length of 56 days, were recorded in 270 of the 280 participants. Results of the investigators' analyses indicated there was considerable variability in treatment responses between individuals (P <.001). Investigators highlighted the greatest differences were observed for choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Further analysis indicated personalized treatment had the potential to provide an additional 4.4 mmHg reduction in systolic blood pressure.¹

“If we personalize each patient’s medication, we can achieve a better effect than if we choose a drug from one of these four drug groups at random. Our study shows that given the right blood pressure drug, the patient can lower their blood pressure and as a result can probably obtain better protection against future cardiovascular diseases more quickly,” Sundström said.²

References

1. Sundström J, Lind L, Nowrouzi S, et al. Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial. JAMA. 2023;329(14):1160–1169. doi:10.1001/jama.2023.3322
2. Bäckström E. Personalised blood pressure treatment more effective. Personalised blood pressure treatment more effective - Uppsala University, Sweden. https://www.uu.se/en/news/article/?id=20562&typ=artikel. Published April 12, 2023. Accessed April 13, 2023.
3. Iapoce C. Rates of hypertension double globally between 1990 - 2019. HCP Live. https://www.hcplive.com/view/rates-of-hypertension-double-globally-between-1990---2019. Published August 24, 2021. Accessed April 14, 2023.