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      Long-Term Blood Pressure Control After Hypertensive Pregnancy Following Physician-Optimized Self-Management : The POP-HT Randomized Clinical Trial

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          Abstract

          Importance

          Pregnancy hypertension results in adverse cardiac remodeling and higher incidence of hypertension and cardiovascular diseases in later life.

          Objective

          To evaluate whether an intervention designed to achieve better blood pressure control in the postnatal period is associated with lower blood pressure than usual outpatient care during the first 9 months postpartum.

          Design, Setting, and Participants

          Randomized, open-label, blinded, end point trial set in a single hospital in the UK. Eligible participants were aged 18 years or older, following pregnancy complicated by preeclampsia or gestational hypertension, requiring antihypertensive medication postnatally when discharged. The first enrollment occurred on February 21, 2020, and the last follow-up, November 2, 2021. The follow-up period was approximately 9 months.

          Interventions

          Participants were randomly assigned 1:1 to self-monitoring along with physician-optimized antihypertensive titration or usual postnatal care.

          Main Outcomes and Measures

          The primary outcome was 24-hour mean diastolic blood pressure at 9 months postpartum, adjusted for baseline postnatal blood pressure.

          Results

          Two hundred twenty participants were randomly assigned to either the intervention group (n = 112) or the control group (n = 108). The mean (SD) age of participants was 32.6 (5.0) years, 40% had gestational hypertension, and 60% had preeclampsia. Two hundred participants (91%) were included in the primary analysis. The 24-hour mean (SD) diastolic blood pressure, measured at 249 (16) days postpartum, was 5.8 mm Hg lower in the intervention group (71.2 [5.6] mm Hg) than in the control group (76.6 [5.7] mm Hg). The between-group difference was −5.80 mm Hg (95% CI, −7.40 to −4.20; P < .001). Similarly, the 24-hour mean (SD) systolic blood pressure was 6.5 mm Hg lower in the intervention group (114.0 [7.7] mm Hg) than in the control group (120.3 [9.1] mm Hg). The between-group difference was −6.51 mm Hg (95% CI, −8.80 to −4.22; P < .001).

          Conclusions and Relevance

          In this single-center trial, self-monitoring and physician-guided titration of antihypertensive medications was associated with lower blood pressure during the first 9 months postpartum than usual postnatal outpatient care in the UK.

          Trial Registration

          ClinicalTrials.gov Identifier: NCT04273854

          Related collections

          Most cited references40

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          Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies

          Objectives To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment. Design Meta-analysis. Data source Medline (1966-2007). Study selection Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) (“blood pressure difference trials”), and 46 trials compared drugs (“drug comparison trials”). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people. Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke. Results In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%). Conclusions With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.
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            Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses.

            Preeclampsia affects 3% to 5% of gestations and eclampsia 0.05% to 0.93%, but their subsequent cardiovascular sequelae are unclear. The aim of this study was to determine if women with a history of preeclampsia/eclampsia are at increased risk of long-term cardiovascular sequelae. From Medline and Embase searches, we included case-control and cohort studies that examined cardiac, cerebrovascular or peripheral arterial disease, or cardiovascular mortality>6 weeks postpartum, in women with and without a history of preeclampsia/eclampsia and that controlled for or matched for confounders. Two independent reviewers determined study eligibility and extracted data. Five case-control and 10 cohort studies met eligibility criteria, with a total of 116,175 women with and 2,259,576 women without preeclampsia/eclampsia. Most studies focused on women<56 years of age. Relative to women with uncomplicated pregnancies, women with a history of preeclampsia/eclampsia had an increased risk of subsequent cardiac disease in both the case-control studies (odds ratio 2.47, 95% CI 1.22-5.01) and the cohort studies (relative risk [RR] 2.33, 1.95-2.78), as well as an increased risk of cerebrovascular disease (RR 2.03, 1.54-2.67), peripheral arterial disease (RR 1.87, 0.94-3.73), and cardiovascular mortality (RR 2.29, 1.73-3.04). Meta-regression revealed a graded relationship between the severity of preeclampsia/eclampsia and the risk of cardiac disease (mild: RR 2.00, 1.83-2.19, moderate: RR 2.99, 2.51-3.58, severe: RR 5.36, 3.96-7.27, P<.0001). Women with a history of preeclampsia/eclampsia have approximately double the risk of early cardiac, cerebrovascular, and peripheral arterial disease, and cardiovascular mortality. Further research is needed to determine the mechanisms underlying these associations and to identify effective prevention strategies.
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              Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

              The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of stroke among individuals who have not previously experienced a stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches to atherosclerotic disease of the cervicocephalic circulation, and antithrombotic treatments for preventing thrombotic and thromboembolic stroke. Further recommendations are provided for genetic and pharmacogenetic testing and for the prevention of stroke in a variety of other specific circumstances, including sickle cell disease and patent foramen ovale.
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                Author and article information

                Journal
                JAMA
                JAMA
                American Medical Association (AMA)
                0098-7484
                November 11 2023
                Affiliations
                [1 ]Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
                [2 ]Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom
                [3 ]Mercy Hospital for Women, Department of Obstetrics and Gynecology, Heidelberg, Australia
                [4 ]Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, United Kingdom
                [5 ]Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
                [6 ]Institute for Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom
                [7 ]School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom
                [8 ]Fetal Medicine Unit, St George’s University Hospitals NHS Foundation Trust, London, United Kingdom
                [9 ]Molecular Clinical Sciences Research Institute, St George’s University of London, London, United Kingdom
                [10 ]King’s College London, London, United Kingdom
                [11 ]Guy’s St Thomas’ NHS Foundation Trust, London, United Kingdom
                Article
                10.1001/jama.2023.21523
                37950919
                bd290ef0-59af-494d-a043-1c56550bbf8d
                © 2023
                History

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