Physicians' Academy for Cardiovascular Education

Substantial variation in SBP response to common antihypertensive drugs

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial

Literature - Sundström J, Lind L, Nowrouzi S, et al. - JAMA. 2023 Apr 11;329(14):1160-1169. doi: 10.1001/jama.2023.3322

Introduction and methods


While multiple classes of highly effective blood pressure (BP)–lowering drugs are widely available [1], it is unknown whether the optimal choice of BP-lowering therapy varies between patients and whether personalized hypertension treatment can maximize clinical benefit.

Aim of the study

The study aim was to investigate and quantify the potential for personalized drug therapy in hypertension to maximize BP-lowering effects.


The PHYSIC (Precision Hypertension Care) trial was a randomized, double-blind, repeated crossover trial conducted at an outpatient research clinic of the Uppsala University Hospital in Sweden. In this trial, 280 patients aged 40–75 years with grade 1 hypertension (i.e., systolic BP (SBP): 140–159 mmHg) who were pharmacologically untreated or used BP-lowering monotherapy at inclusion (indicating a low-risk primary prevention sample) were included.

After completion of a 2-week run-in period with placebo, participants were assigned to a sequence of 6 treatment periods administered in random order. A treatment period (7–9 weeks’ duration) consisted of treatment with candesartan 16 mg (ARB), lisinopril 20 mg (ACEi), amlodipine 10 mg (calcium channel blocker), or hydrochlorothiazide 25 mg (thiazide). In addition, every patient repeated 2 of the treatment periods selected at random. Between each treatment period, there was a 1-week washout period with placebo. The primary analysis of the trial comprised 1486 completed treatment periods (median length: 56 days) in 270 patients.


The primary endpoint was daytime (10:00–20:00 h) ambulatory SBP, measured at the end of each treatment period.

Main results

Variability in drug treatment effects

Potential for personalized treatment


The Swedish PHYSIC trial showed that the SBP response to 4 widely used antihypertensive drug classes varied considerably between patients with hypertension. Personalized treatment had the potential to lower SBP by 4.4 mmHg compared with a fixed drug choice.


Show references

Find this article online at JAMA.

Share this page with your colleagues and friends: