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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.

SUBMITTER: Kronish IM

PROVIDER: S-EPMC6544735 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Kronish Ian M IM Cheung Ying Kuen YK Shimbo Daichi D Julian Jacob J Gallagher Benjamin B Parsons Faith F Davidson Karina W KW

Journal of general internal medicine 20190311 6

<h4>Background</h4>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.<h4>Objective</h4>To determine the feasibility of individualizing the selection of BP medications through pragmatic personalized (i.e., N-of-1) trials.<h4>Design</h4>Series of N-of-1 trials.<h4>Setting</h4>Outpatient.<h4>Patients</h4>Hypertensive adults prescribed none or one BP medicati ...[more]

PMID: 30859504

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Project description:Background:Two recent randomized trials produced discordant results when testing the benefits and harms of treatment to reduce blood pressure (BP) in patients with cardiovascular disease (CVD). Objective:To perform a theoretical modeling study to identify whether large, clinically important differences in benefit and harm among patients (heterogeneous treatment effects [HTEs]) can be hidden in, and explain discordant results between, treat-to-target BP trials. Design:Microsimulation. Data Sources:Results of 2 trials comparing standard (systolic BP target <140 mm Hg) with intensive (systolic BP target <120 mm Hg) BP treatment and data from the National Health and Nutrition Examination Survey (2013 to 2014). Target Population:U.S. adults. Time Horizon:5 years. Perspective:Societal. Intervention:BP treatment. Outcome Measures:CVD events and mortality. Results of Base-Case Analysis:Clinically important HTEs could explain differences in outcomes between 2 trials of intensive BP treatment, particularly diminishing benefit with each additional BP agent (for example, adding a second agent reduces CVD risk [hazard ratio, 0.61], but adding a fourth agent to a third has no benefit) and increasing harm at low diastolic BP. Results of Sensitivity Analysis:Conventional treat-to-target trial designs had poor (<5%) statistical power to detect the HTEs, despite large samples (n > 20 000), and produced biased effect estimates. In contrast, a trial with sequential randomization to more intensive therapy achieved greater than 80% power and unbiased HTE estimates, despite small samples (n = 3500). Limitations:The HTEs as a function of the number of BP agents only were explored. Simulated aggregate data from the trials were used as model inputs because individual-participant data were not available. Conclusion:Clinically important heterogeneity in intensive BP treatment effects remains undetectable in conventional trial designs but can be detected in sequential randomization trial designs. Primary Funding Source:National Institutes of Health and U.S. Department of Veterans Affairs.

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

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

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