Increasing the Precision of Hypertension Treatment Through Personalized Trials: a Pilot Study

Abstract

BACKGROUND: There are substantial differences in the effects of blood pressure (BP) medications in individual patients. Yet, the current standard approach to prescribing BP medications is not personalized. OBJECTIVE: To determine the feasibility of individualizing the selection of BP medications through pragmatic personalized (i.e., N-of-1) trials. DESIGN: Series of N-of-1 trials. SETTING: Outpatient. PATIENTS: Hypertensive adults prescribed none or one BP medication. INTERVENTION: Participation in a flexible, open-label personalized trial of two to three BP medications (NCT02744456). MEASUREMENTS: BP was measured twice per day with a validated home BP device. Frequency and severity of side effects were assessed at the end of the day via an electronic questionnaire. Patients' BP medication preference was assessed after reviewing BP lowering and side effect results with a study clinician. Feasibility was assessed by determining the proportion of patients who adhered to self-assessments. Benefit was assessed by asking patients to rate the helpfulness of participation and whether they would recommend personalized trials to other hypertensive patients. KEY RESULTS: Of ten patients enrolled, two dropped out prior to initiation, one discovered white coat hypertension through ambulatory BP monitoring, and seven (mean age 58 years, 71% of women) completed personalized trials. All seven were compliant with home BP monitoring and side effect tracking. All seven recommended personalized trials of BP medications to others. Thiazides were preferred by three patients, renin-angiotensin system-blocking agents by two patients, a combination of thiazide and beta-blocker by one patient, and any of three classes by one patient. CONCLUSIONS: Personalized trials of BP medications were feasible and led to improved treatment precision. Heterogeneity of patient preferences and of therapeutic BP response for first-line BP medications can be determined through a personalized trial approach.

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“…Another alternative, for patients with genetic markers that correlate with the anticipated activity of a test intervention, is the N-of-1 trial. 109 Here, the patient serves as his/her own control. The success of the therapy, or basis for continuation, can be based for example on blood levels of selected metabolites and proteins that should lead to reduced disease or tumor growth.…”

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“…Because of the cross-over design, these studies are most suitable for the evaluation of treatments with rapid effect onset, and for diseases in which patients quickly return to a stable baseline after treatment, without any significant carryover effect [ 83 ]. This is why N-of-1 studies have so far mainly been used for chronic diseases, such as arthritis, fibromyalgia, chronic airflow limitation, gastric reflux, hypertension, and others [ 68 , 74 , 84 ]. Regarding future use, the recommended therapeutic areas for N-of-1 trials include diabetes, glaucoma, hyperlipidemia, and asthma [ 78 ].…”