Patients may respond differently to different hypertension drug classes
The authors of a randomized, double-blind, repeated crossover trial in Sweden estimated that personalized antihypertensive therapy could yield an average reduction in systolic blood pressure of 4.4 mm Hg compared to fixed-choice therapy.
Patients with hypertension may respond differently to different classes of antihypertensive drugs, according to a recent study.
In a randomized, double-blind, repeated crossover trial in outpatients with hypertension and low risk for cardiovascular events, researchers in Sweden used mixed-effects models to assess responses to one treatment over another and estimate the potential benefit of targeting specific drugs to specific individuals. After a two-week placebo run-in period, each patient was assigned to a six-week sequence of treatments in random order. Every patient was treated with 20 mg of lisinopril, an angiotensin-converting enzyme inhibitor; 16 mg of candesartan, an angiotensin-receptor blocker; 25 mg of hydrochlorothiazide, a thiazide; and 10 mg of amlodipine, a calcium-channel blocker. Treatments were repeated at random for two classes. Each treatment period lasted seven to nine weeks, with half-doses during weeks one and two and full doses during weeks three through nine. A one-week washout period with placebo occurred between each treatment period. The study's main outcome measure was ambulatory systolic blood pressure at the end of each treatment period. The results were published April 11 by JAMA.
A total of 1,468 completed treatment periods with a median length of 56 days were recorded in 270 of 280 randomized participants (54% men, mean age 64 years). Individuals' responses to different antihypertensive treatments showed considerable variation (P<0.001), specifically for lisinopril versus hydrochlorothiazide, lisinopril versus amlodipine, candesartan versus hydrochlorothiazide, and candesartan versus amlodipine. There were no large differences in response with candesartan versus lisinopril or amlodipine versus hydrochlorothiazide, indicating that choice of therapy within these pairs of drugs would not be consequential, the researchers said. They estimated that personalized treatment for hypertension had the potential to yield an additional 4.4 mm Hg reduction in systolic blood pressure, on average.
Limitations of the trial included imperfect adherence and a focus on monotherapy. The researchers concluded that their study indicates substantial heterogeneity in blood pressure response to drug therapy for hypertension. “Given the size of the likely benefits, additional studies to confirm these findings, to test for the potential of personalization of combination antihypertensive therapy, and to identify mechanisms to enable the personalization of antihypertensive therapy in routine clinical practice should be a priority,” they wrote.
The author of an accompanying editorial pointed out that the study participants' systolic blood pressure at baseline was 140 to 159 mm Hg, indicating stage 2 hypertension according to U.S. definitions, and that their risk for atherosclerotic cardiovascular disease was not formally assessed, as U.S. guidelines recommend. The editorialist also noted that blood pressure reduction is a surrogate marker of such conditions as ischemic heart disease and myocardial infarction.
“The results of this study encourage the further pursuit of larger randomized trials using similar repeated crossover designs to validate this concept and eventually in trials with longer follow-up data to determine whether there is improvement in long-term clinical outcomes compared with current strategies,” he wrote. “In the meantime, the results of this study support the possibility that personalized medical treatment of hypertension may ultimately supplement or even supplant the current method of antihypertensive drug decision making in the future.”