NEW YORK (Reuters Health) – There is no single blood pressure-lowering drug that works for most hypertensive children, but single-patient randomized crossover trials (n-of-1 trials) can be used to optimize their management, researchers report.
The 2017 American Academy of Pediatrics Clinical Practice Guidelines do not specify a particular agent or class of antihypertensive as first-line therapy for children with hypertension.
Dr. Joyce P. Samuel and colleagues from McGovern Medical School at UT Health, in Houston, conducted n-of-1 trials in 32 children diagnosed with primary hypertension.
They prescribed three commonly used therapies (amlodipine, hydrochlorothiazide, and lisinopril) in randomized order for two-week treatment periods. Next, they did a second cycle of testing, this time trialing two medications for two-week treatment periods. To narrow the choice of medication from three to two, they excluded a medication if it produced an unacceptable side effect. If there were no unacceptable side effects, then the two medications that produced the greatest reductions in mean awake systolic blood pressure were retested in the second cycle.
No single medication was preferred for the majority of patients, though lisinopril was the preferred medication for the largest proportion of children (49%).
The preferred medication identified by the n-of-1 trials was generally not the same as prescribed before the study, with only 20% of patients continuing on the same medication, the researchers report in Pediatrics, online March 6.
Six children had been taking multiple antihypertensive medications at enrollment, and five of these achieved adequate blood pressure control on monotherapy after the n-of-1 trial.
There were only modest overall differences between medications, but individual participants differed considerably in the measured effects on their blood pressure, with median differences between best-performing and worst-performing medications of 12 mm Hg (interquartile range, 6-21 mm Hg).
“This individualized approach to antihypertensive medication selection holds potential value by involving patients in their own care and facilitating informed treatment decisions,” the researchers conclude. “In usual care, the choice of specific antihypertensive regimen is based on physician preference with little or no systematic assessment of treatment benefits and hazards.”
“A randomized trial in which researchers compare usual care to routine use of n-of-1 trials with ABPM (ambulatory blood pressure monitoring) is needed to assess effects on treatment adherence, patient satisfaction, long-term BP control assessed with ABPM, and hypertensive target organ damage,” they add.
Dr. David C. Kaelber from Case Western Reserve University, in Cleveland, Ohio, who studies pediatric hypertension, told Reuters Health by email, “Personalized medicine is one of those ‘buzz words’ folks use a lot, but this is one of the first truly practical and effective example of personalized medicine that I have seen in pediatrics, outside of pediatric oncology.”
“One of the weaknesses of the approach is the extra time and other resources need to conduct the n-of-1 study in order to determine the best treatment for the patient,” he said.
“If your practice and patient/family with confirmed pediatric hypertension has the interest, time, and resources, the n-of-1 trials approach allows you to personalize medication treatment for pediatric hypertension,” Dr. Kaelber said.
“The n-of-1 trials approach could potentially be applied to other pediatric and adult chronic conditions where multiple treatments may be appropriate for an individual patient and the physician and patient/family want to try a more personalized medicine approach,” he said.
Dr. Samuel did not respond to a request for comments.