Personalized targeted antihypertensive monotherapy linked to best BP control: JAMA
Sweden: Findings from the PHYSIC randomized trial have revealed sizable differences in individual responses to drug therapy for hypertension and may have implications for personalized treatment. The study showed that patients treated with antihypertensives could experience much greater improvements from a medication change than from doubling the dose of their current medication.
"Our findings show heterogeneity in blood pressure (BP) response to drug therapy for hypertension of a magnitude that warrants further exploration," the researchers wrote in their study published in the Journal of the American Medical Association (JAMA). Careful testing showed people which BP-lowering medications worked best for them, an early step toward making personalized hypertension treatment a potential reality.
In the study from Uppsala University, 280 hypertension patients taking one of four drugs randomly led to different responses in ambulatory daytime systolic blood pressure. Between patients, treatment responses of monotherapy differed the most between hydrochlorothiazide versus angiotensin-converting enzyme inhibitor lisinopril, calcium channel blocker amlodipine versus lisinopril, candesartan versus amlodipine, and hydrochlorothiazide versus the angiotensin-receptor blocker candesartan.
Hypertension is a common risk factor for worldwide premature death. Though multiple BP-lowering therapies are available, there is no information on the potential for maximizing benefits by personalized targeting of drug classes. To fill this knowledge gap, Johan Sundström, Uppsala University, Uppsala, Sweden, and colleagues aimed to investigate and quantify the potential for targeting specific drugs to specific individuals to maximize BP effects.
For this purpose, the researchers conducted a double-blind, randomized, repeated crossover trial in women and men with grade 1 hypertension at low CV (cardiovascular) events risk at an outpatient research clinic in Sweden. They assessed the extent to which individuals responded better to one treatment than another using mixed-effects models and estimated the additional BP lowering achievable by personalized medicine.
Each participant was randomly scheduled for treatment with four different blood pressure-lowering drugs (lisinopril, candesartan, hydrochlorothiazide, and amlodipine) with repeated treatment for two classes.
Ambulatory daytime systolic blood pressure was measured at the end of each treatment period.
The authors reported the following findings:
- There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years).
- The blood pressure response to different treatments varied considerably between individuals, specifically for the choices of lisinopril vs amlodipine, lisinopril vs hydrochlorothiazide, candesartan vs amlodipine, and candesartan vs hydrochlorothiazide.
- Significant differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine.
- On average, personalized treatment could provide an additional 4.4 mm Hg–lower systolic blood pressure.
"The data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, results that may have implications for personalized therapy," the authors concluded.
Reference:
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
