Dataset Information

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial.

ABSTRACT:

Importance

Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown.

Objective

To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects.

Design, setting, and participants

A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment.

Interventions

Each participant was scheduled for treatment in random order with 4 different classes of blood pressure-lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes.

Main outcomes and measures

Ambulatory daytime systolic blood pressure, measured at the end of each treatment period.

Results

There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P < .001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure.

Conclusions and relevance

These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy.

Trial registration

ClinicalTrials.gov Identifier: NCT02774460.

SUBMITTER: Sundstrom J

PROVIDER: S-EPMC10091169 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial.

Sundström Johan J Lind Lars L Nowrouzi Shamim S Hagström Emil E Held Claes C Lytsy Per P Neal Bruce B Marttala Kerstin K Östlund Ollie O

JAMA 20230401 14

<h4>Importance</h4>Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown.<h4>Objective</h4>To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects.<h4>Design, setting, and participants</h4>A randomized, double-blind, repeated crossover trial in men and women ...[more]

PMID: 37039792

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Project description:Patient empowerment through pharmacological self-management is a common strategy in some chronic diseases such as diabetes, but it is rarely used for controlling blood pressure. This study aimed to assess self-monitoring plus self-titration of antihypertensive medication versus usual care for reducing systolic blood pressure (SBP) at 12 months in poorly controlled hypertensive patients. The ADAMPA study was a pragmatic, controlled, randomized, non-masked clinical trial with two parallel arms in Valencia, Spain. Hypertensive patients older than 40 years, with SBP over 145 mmHg and/or diastolic blood pressure (DBP) over 90 mmHg, were recruited from July 2017 to June 2018. Participants were randomized 1:1 to usual care versus an individualized, pre-arranged plan based on self-monitoring plus self-titration. The primary outcome was the adjusted mean difference (AMD) in SBP between groups at 12 months. Primary outcome data were available for 312 patients (intervention n=156, control n=156) of the 366 who were initially recruited. The AMD in SBP at 12 months (main analysis) was -2.9 mmHg (95% CI, -5.9 to 0.1, p=0.061), while the AMD in DBP was -1.9 mmHg (95% CI, -3.7 to 0.0, p=0.052). The results of the subgroup analysis were consistent with these for the main outcome measures. More patients in the intervention group achieved good blood pressure control (<140/90 mmHg) at 12 months than in the control group (55.8% vs 42.3%, difference 13.5%, 95% CI, 2.5 to 24.5%, p=0.017). At 12 months, no differences were observed in behavior, quality of life, use of health services, or adverse events. Self-monitoring plus self-titration of antihypertensive medication based on an individualized pre-arranged plan used in primary care may be a promising strategy for reducing blood pressure at 12 months compared to usual care, without increasing healthcare utilization or adverse events. EudraCT, number 2016-003986-25 (registered 17 March 2017) and clinicaltrials.gov , NCT03242785.

Project description:Aims/hypothesisOur aim was to evaluate the safety and efficacy of a planned therapeutic withdrawal of all antihypertensive and diuretic medications, on commencing a formula low-energy diet replacement, targeting remission of type 2 diabetes.MethodsPost hoc analysis of changes in BP, antihypertensive medication prescriptions and symptoms during the initial total diet replacement phase was performed in the intervention arm of the Diabetes Remission Clinical Trial (n = 143) and in the subset (n = 69) who discontinued antihypertensive medications at the start of total diet replacement. The Counterweight-Plus total diet replacement provided about 3470 kJ/day (830 kcal) with automatic reductions in all nutrients, including sodium, to achieve marked negative energy balance and rapid weight loss over 12-20 weeks, with regular BP monitoring and an antihypertensive reintroduction protocol based on current clinical guidelines.ResultsOf 143 intervention group participants who commenced total diet replacement, 78 (55%) were on treatment for hypertension at baseline. The overall mean BP fell significantly from the start of total diet replacement (week 1) and was significantly lower at week 20, after total diet replacement finished, and also at 12 and 24 months. Of the 78 participants previously on treatment for hypertension, 65 (83%) stopped all antihypertensive and diuretic medications as per protocol, and four (5%) stopped some drugs. These 69 participants experienced no immediate (within the first week) change in BP, but their mean BP fell significantly from 9 weeks. No excessive rises in BP were recorded in individuals, but antihypertensive medications were reintroduced during total diet replacement to manage raised BP for 19/69 (27.5%) participants, mostly within the first 3-7 weeks, despite some weight loss. Reintroduction of antihypertensive medications was necessary for 5/19 participants previously on one drug, and for 14/19 previously on two or more drugs. Of the 69 who stopped antihypertensives, 19 (28%) remained off medications at 24 months. Among the 53 participants who achieved sustained remissions of diabetes at 24 months (with a mean weight loss of 11.4 kg), 31 had been previously treated for hypertension. Twenty-seven stopped medication at baseline, and 15/27 required reintroduction of antihypertensive medications. Mild to moderate dizziness, suggesting some postural hypotension, was reported during total diet replacement by 51 participants, 15 of whom had recorded dizziness at baseline prior to starting total diet replacement, with nine of these on antihypertensive or diuretic medications.Conclusions/interpretationReplacing antihypertensive medications with a 3470 kJ/day (830 kcal) diet to induce weight loss reduces BP substantially and may increase mild dizziness. It is safe to stop antihypertensives, but BP should be monitored regularly, particularly for those taking two or more antihypertensives, as over two-thirds will require reintroduction of some medications. Long-term support to maintain weight loss is vital.Trial registrationISRCTN registry, number 03267836.

Project description:ImportanceOnly about half of patients with high blood pressure (BP) in the United States have their BP controlled. Practical, robust, and sustainable models are needed to improve BP control in patients with uncontrolled hypertension.ObjectivesTo determine whether an intervention combining home BP telemonitoring with pharmacist case management improves BP control compared with usual care and to determine whether BP control is maintained after the intervention is stopped.Design, setting, and patientsA cluster randomized clinical trial of 450 adults with uncontrolled BP recruited from 14,692 patients with electronic medical records across 16 primary care clinics in an integrated health system in Minneapolis-St Paul, Minnesota, with 12 months of intervention and 6 months of postintervention follow-up.InterventionsEight clinics were randomized to provide usual care to patients (n = 222) and 8 clinics were randomized to provide a telemonitoring intervention (n = 228). Intervention patients received home BP telemonitors and transmitted BP data to pharmacists who adjusted antihypertensive therapy accordingly.Main outcomes and measuresControl of systolic BP to less than 140 mm Hg and diastolic BP to less than 90 mm Hg (<130/80 mm Hg in patients with diabetes or chronic kidney disease) at 6 and 12 months. Secondary outcomes were change in BP, patient satisfaction, and BP control at 18 months (6 months after intervention stopped).ResultsAt baseline, enrollees were 45% women, 82% white, mean (SD) age was 61.1 (12.0) years, and mean systolic BP was 148 mm Hg and diastolic BP was 85 mm Hg. Blood pressure was controlled at both 6 and 12 months in 57.2% (95% CI, 44.8% to 68.7%) of patients in the telemonitoring intervention group vs 30.0% (95% CI, 23.2% to 37.8%) of patients in the usual care group (P = .001). At 18 months (6 months of postintervention follow-up), BP was controlled in 71.8% (95% CI, 65.0% to 77.8%) of patients in the telemonitoring intervention group vs 57.1% (95% CI, 51.5% to 62.6%) of patients in the usual care group (P = .003). Compared with the usual care group, systolic BP decreased more from baseline among patients in the telemonitoring intervention group at 6 months (-10.7 mm Hg [95% CI, -14.3 to -7.3 mm Hg]; P<.001), at 12 months (-9.7 mm Hg [95% CI, -13.4 to -6.0 mm Hg]; P<.001), and at 18 months (-6.6 mm Hg [95% CI, -10.7 to -2.5 mm Hg]; P = .004). Compared with the usual care group, diastolic BP decreased more from baseline among patients in the telemonitoring intervention group at 6 months (-6.0 mm Hg [95% CI, -8.6 to -3.4 mm Hg]; P<.001), at 12 months (-5.1 mm Hg [95% CI, -7.4 to -2.8 mm Hg]; P<.001), and at 18 months (-3.0 mm Hg [95% CI, -6.3 to 0.3 mm Hg]; P = .07).Conclusions and relevanceHome BP telemonitoring and pharmacist case management achieved better BP control compared with usual care during 12 months of intervention that persisted during 6 months of postintervention follow-up.Trial registrationclinicaltrials.gov Identifier: NCT00781365.

Dataset Information

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial.

Similar Datasets

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