A new study has shown a substantial variation in the blood pressure response to various antihypertensive medications between individuals, raising the possibility of future personalized therapy.
“We found that using the optimal antihypertensive drug for a particular patient resulted in an average of a 4.4 mm Hg greater reduction of blood pressure compared with a random choice of the other drugs. That is quite a substantial difference, and could be equivalent to adding in another drug,” lead author Johan Sundström, MD, Uppsala (Sweden) University Hospital, told this news organization.
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“These preliminary findings suggest that some people may be better treated with one antihypertensive drug rather than another. This is opening up the field of hypertension for personalized medicine,” he added.
The study was published online in the Journal of the American Medical Association.
The authors noted that despite global access to multiple classes of highly effective blood pressure-lowering drugs, only one in four women and one in five men with hypertension reach treatment targets. 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.
“One drug often does not give enough blood pressure reduction, but patients are often reluctant to up-titrate to two drugs,” Dr. Sundström said. “While we know that the four recommended classes of antihypertensives lower blood pressure equally well on average, we don’t know if their efficacy is the same in individual patients.
“We wondered whether there could be different optimal drugs for different people, and if we could identify the optimal drug for each person then maybe more patients could get to target levels with just one drug,” he said.
The researchers conducted a randomized, double-blind, repeated crossover trial at an outpatient research clinic in Sweden, studying 280 men and women with grade 1 hypertension at low risk for cardiovascular events.
Each participant was scheduled for 2 months’ treatment in random order with each of four different classes of antihypertensive drugs: an ACE inhibitor, lisinopril; an angiotensin II blocker, candesartan; a thiazide diuretic, hydrochlorothiazide; a calcium channel blocker, amlodipine.
There were then repeated treatment periods for two drug classes to try to account for any effect of a particular event that might have affected the blood pressure at one point in time. Ambulatory daytime systolic blood pressure was measured at the end of each treatment period.
Results showed that variation in systolic blood pressure was large between treatments on average, between participants on average, within participants taking the same treatment, and between treatments in the same participant.
Overall, personalized treatment using the optimal single-drug therapy led to a 4.4–mm Hg lower systolic blood pressure in the trial population than a random choice of any of the other drug classes.
Taking into consideration that lisinopril was found to be on average the most efficacious of the drugs at the selected doses, personalized treatment compared with lisinopril still led to a 3.1–mm Hg improvement in systolic blood pressure.
The researchers noted that the mean additional blood pressure reduction achievable by using the optimal agent was of a magnitude twice that achieved by doubling the dose of a first drug, and more than half that of adding a second drug on average.
While there were only small differences between certain drugs (e.g., candesartan vs. lisinopril; amlodipine vs. hydrochlorothiazide), for all other comparisons tested, the choice was important, with particularly large gains to be made by personalizing the choice between candesartan vs. amlodipine and between lisinopril vs. amlodipine.
In addition, some people showed very large differences in response to different drugs, whereas others did not have much difference at all.