Matching People to Specific BP Meds in a Sea of Antihypertensives

Careful testing showed people which blood pressure (BP) lowering medications worked best for them, an early step to making personalized hypertension treatment a potential reality.

In the PHYSIC randomized trial, hypertension patients taking one of four drugs in random order produced different responses in ambulatory daytime systolic BP. Between individuals, monotherapy treatment responses differed the most between the angiotensin-converting enzyme inhibitor lisinopril vs hydrochlorothiazide, lisinopril vs the calcium channel blocker amlodipine, the angiotensin-receptor blocker candesartan vs hydrochlorothiazide, and candesartan vs amlodipine.

On average, personalized monotherapy showed the potential to provide an additional 4.4 mm Hg lower systolic BP after each person was given nearly 2 months on each medication to control for normal within-person variation in BP, according to Johan Sundström, MD, PhD, of Uppsala University Hospital in Sweden, and colleagues.

"This study provided evidence that widely used antihypertensive drugs vary in effectiveness between individuals, with potential for greater BP reductions with personalized targeting of therapy. The mean additional BP reduction achievable was substantial, of a magnitude twice that achieved by doubling the dose of a first BP-lowering drug, and more than half that of adding a second drug on average," the PHYSIC investigators reported in JAMA.

"Considering noninvasive, wearable BP measurement devices under development, it is possible to imagine a future where continuous BP measurement could differentiate between the effectiveness of multiple drug therapies provided to patients in standardized n-of-1 testing protocols," the team wrote. "Of note, this study does not propose the year-long process for each patient used in this trial to identify an individual's optimal treatment."

Indeed, personally targeted BP therapy is not yet feasible and the right path to get there is unclear, suggested Robert Carey, MD, of University of Virginia Health System in Charlottesville, in an accompanying editorial.

He called subjecting an individual to a series of n-of-1 tests of antihypertensives "too cumbersome," but said there are still very few phenotypic markers available to otherwise predict one's personal BP response to monotherapy.

The editorialist also stressed that PHYSIC's results were based on BP, a surrogate endpoint.

"While there is no question that high BP aligns with increased cardiovascular disease risk and that controlling BP unequivocally reduces this risk, further evidence is needed from larger randomized trials to determine clinical outcomes using a personalized targeted approach to hypertension treatment," Carey cautioned.

PHYSIC (Precision Hypertension Care Study) was a randomized trial, with a double-blind, repeated crossover design, conducted at an outpatient clinic. Participants were adults with stage 2 hypertension who were untreated or on BP-reducing monotherapy.

There were 280 people randomized (54% men, mean age 64 years), of which 270 completed 1,468 drug treatment periods in aggregate (median length 56 days). The cohort had had hypertension for an average 3 years, 62.1% had previously used BP-lowering monotherapy, and the mean office BP after placebo run-in was 154/89 mm Hg.

Sundström's group acknowledged that the narrow selection of patients limits PHYSIC's generalizability to other individuals and other drug classes. Moreover, the trial did not address personalization of combination therapy, which is recommended by American guidelines.

"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," the authors noted.

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