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Canadian Journal of Cardiology

Advancing Digital Health Interventions as a Clinically Applied Science for Blood Pressure Reduction: A Systematic Review and Meta-analysis

Open AccessPublished:November 15, 2019DOI:https://doi.org/10.1016/j.cjca.2019.11.010

      Abstract

      Background

      Behavioural counselling via internet- or mobile-based digital platforms is recommended for hypertension; however, outcome heterogeneity is problematic in trials of this digital intervention. Our objective was to assess how therapeutic outcome was optimized in digital trials for hypertension, according to key features of the intervention design and protocol.

      Methods

      We identified randomized controlled digital trials for systolic blood pressure (SBP) reduction in taskforce guideline and policy statements, systematic reviews, and meta-analyses published since 2010, by searching the EMBASE, Cochrane Library, psycINFO, and PubMed databases. This search was updated to January 2019. Trials included patients with elevated cardiovascular risk or cardiovascular disease. We classified digital trials by the number of components of the intervention, and whether the protocol was organized by an explicit model of behavioural change or counselling. The influence of these features was evaluated for treatment efficacy and heterogeneity of SBP outcomes.

      Results

      Seventeen trials met inclusion criteria: pooled n = 5780, 33% female, 93% taking antihypertensive medications. SBP reduction was −7.3 mm Hg for digital counselling (95% confidence interval: −7.0 to −7.5) vs −3.6 mm Hg for control (95% confidence interval: −3.4 to −3.9), P < 0.0001, with high-moderate heterogeneity (I2 = 67%). Trials with multiple behavioural intervention components and an organized theoretical framework of behaviour change or counselling demonstrated optimal SBP reduction with low-moderate heterogeneity (I2 = 49%).

      Conclusions

      Digital health interventions optimize the efficacy of medical therapy for SBP reduction. There is opportunity to promote a disruptive change in clinical science that accompanies technological developments in digital health promotion.

      Résumé

      Introduction

      Le counseling comportemental via les plateformes numériques connectées à Internet ou mobiles est recommandé aux personnes atteintes d’hypertension. Toutefois, l’hétérogénéité des résultats est problématique dans les essais de cette intervention numérique. Notre objectif était d’évaluer la façon avec laquelle les résultats thérapeutiques étaient optimisés dans les essais numériques sur l’hypertension, selon les caractéristiques principales de la conception et du protocole de l’intervention.

      Méthodes

      Nous avons trouvé des essais cliniques numériques à répartition aléatoire sur la réduction de la pression artérielle systolique (PAS) dans les recommandations des groupes de travail et les énoncés de politiques, les revues systématiques et les méta-analyses publiées depuis 2010 en effectuant des recherches dans les bases de données EMBASE, Cochrane Library, psycINFO et PubMed. Cette recherche a été actualisée jusqu’en janvier 2019. Les essais regroupaient des patients exposés à un risque cardiovasculaire élevé ou à une maladie cardiovasculaire. Nous avons classifié les essais numériques selon le nombre de composantes de l’intervention, et dans le cas où le protocole était organisé par un modèle explicite de changements ou de counseling comportementaux. Nous avons évalué l’influence de ces caractéristiques sur l’efficacité du traitement et l’hétérogénéité des résultats de la PAS.

      Résultats

      Dix-sept essais répondaient aux critères d’inclusion : n regroupé = 5780, 33 % de femmes, 93 % qui prenaient des antihypertenseurs. La réduction de la PAS était de −7,3 mmHg lors de counseling numérique (intervalle de confiance à 95 % : de −7,0 à −7,5) vs −3,6 mmHg pour les témoins (intervalle de confiance à 95 % : de −3,4 à −3,9), p < 0,0001, et l’hétérogénéité était modérée ou élevée (I2 = 67 %). Les essais portant sur de multiples composantes d’intervention comportementale et un cadre théorique organisé sur la modification et le counseling comportementaux ont démontré une réduction optimale de la PAS et une hétérogénéité basse ou modérée (I2 = 49 %).

      Conclusions

      Les interventions numériques en santé optimisent l’efficacité du traitement médical pour la réduction de la PAS. Il est possible de promouvoir des changements déstabilisants en science clinique qui accompagnent les progrès technologiques en promotion de la santé numérique.
      Elevated systolic blood pressure (SBP) is a leading risk factor in the global burden of disease.
      GBD 2017 Risk Factor Collaborators
      Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
      It accounts for 10.4 million deaths annually and the loss of 218 million disability-adjusted life-years.
      GBD 2017 Risk Factor Collaborators
      Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
      Clinical trial evidence indicates that a 10 mm Hg reduction in SBP is associated with a decrease of 17%-28% in risk for cardiovascular events, and 13% for all-cause mortality.
      • Ettehad D.
      • Emdin C.A.
      • Kiran A.
      • et al.
      Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis.
      There is also a linear association between the magnitude of SBP reduction and risk for cardiovascular events,
      • Bundy J.D.
      • Li C.
      • Stuchlik P.
      • et al.
      Systolic blood pressure reduction and risk of cardiovascular disease and mortality: a systematic review and network meta-analysis.
      which underscores the importance of optimizing antihypertensive drug therapy by promoting patient adherence to recommended self-care behaviours for exercise, diet, and medications. To that end, behavioural counselling reduces SBP between 5 and 10 mm Hg whether it is provided in conventional clinic settings
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • et al.
      2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      or via a digital platform that is internet or mobile based.
      • Lin J.S.
      • O'Connor E.A.
      • Evans C.V.
      • et al.
      Behavioral Counseling to Promote a Healthy Lifestyle for Cardiovascular Disease Prevention in Persons With Cardiovascular Risk Factors: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force.
      ,
      • Liu S.
      • Dunford S.D.
      • Leung Y.W.
      • et al.
      Reducing blood pressure with Internet-based interventions: a meta-analysis.
      In contrast to clinical trials of antihypertensive pharmacotherapy, trials of behavioural counselling for hypertension have demonstrated a persistent problem of heterogeneity of treatment outcomes. Few meta-analytic studies have examined potential sources of outcome variability in these trials. Candidate factors include differences in patient characteristics and disease severity, complexity (number) of treatment components in the counselling protocol, trial duration, and intervention method (eg, mobile or internet based, alone, or with human support).
      • Liu S.
      • Dunford S.D.
      • Leung Y.W.
      • et al.
      Reducing blood pressure with Internet-based interventions: a meta-analysis.
      ,
      • Beishuizen C.R.
      • Stephan B.C.
      • van Gool W.A.
      • et al.
      Web-based interventions targeting cardiovascular risk factors in middle-aged and older people: a systematic review and meta-analysis.
      Recent guideline statements for cardiovascular health promotion
      • Piepoli M.F.
      • Hoes A.W.
      • Agewall S.
      • et al.
      2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
      ,
      • Artinian N.T.
      • Fletcher G.F.
      • Mozaffarian D.
      • et al.
      Interventions to promote physical activity and dietary lifestyle changes for cardiovascular risk factor reduction in adults: a scientific statement from the American Heart Association.
      have advocated a more uniform design for behavioural programs, where (1) the counselling protocol includes numerous procedures to evoke and sustain change in self-care behaviours, and (2) the counselling procedures are organized according to an established theory of behaviour change, or model of behavioural counselling. However, it is not established whether this recommended strategy is sufficient to reduce heterogeneity of treatment outcomes while maintaining an optimal standard of treatment efficacy.
      The objective of this study was to evaluate how key therapeutic components of digitally based behavioural counselling for blood pressure reduction were associated with treatment efficacy and outcome heterogeneity. We focused on clinical trials that have been cited in recent task force policy and guideline statements by cardiovascular societies, and in major systematic reviews, given that these trials have helped to shape current recommendations for cardiovascular health promotion.

      Methods

      We initiated our literature search with a review of taskforce guidelines, scientific statements, and systematic reviews on digital health interventions aimed at improving blood pressure in populations with elevated cardiovascular disease (CVD) risk factors or established CVD. Randomized controlled trials (RCTs) were then selected and reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline, and the Cochrane Handbook of Systematic Reviews of Interventions Version 5.1.0.
      • Higgins J.P.
      • Deeks J.J.
      Selecting studies and collecting data.

      Study selection

      We performed a comprehensive literature search in the EMBASE, Cochrane Library, psycINFO, and PubMed databases, to identify relevant peer-reviewed taskforce guidelines, scientific statements, systematic reviews, and meta-analyses published since 2010. The search terms “cardiac health,” “systematic review,” “mHealth,” “eHealth,” “behavioural intervention,” “hypertension,” “blood pressure,” “cardiovascular disease,” “heart health,” “behaviour change,” “meta-analysis,” “CVD risk factor,” “prevention,” “heart failure,” and “self-care” were used. To minimize the risk of failing to identify relevant reviews, we conducted a manual search of key journals and reference lists in recent reviews and guideline statements that were captured by the initial literature search. A comprehensive database search for individual RCTs was also performed to identify new trials that were published after the most recent citation in our sample of task force statements and systematic reviews. This database search followed the same procedures as noted above, and it spanned the interval between January 2017 and January 2019. We also contacted the authors of trials that were potentially relevant to this study to ascertain if they met our inclusion criteria. Each extracted title and abstract was reviewed for relevance to this study and duplication, before conducting full-text screening.

      Inclusion and exclusion criteria

      Inclusion criteria for this systematic review followed key features noted in previous meta-analyses from which our RCTs were obtained.
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • et al.
      2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      ,
      • Liu S.
      • Dunford S.D.
      • Leung Y.W.
      • et al.
      Reducing blood pressure with Internet-based interventions: a meta-analysis.
      • Beishuizen C.R.
      • Stephan B.C.
      • van Gool W.A.
      • et al.
      Web-based interventions targeting cardiovascular risk factors in middle-aged and older people: a systematic review and meta-analysis.
      • Piepoli M.F.
      • Hoes A.W.
      • Agewall S.
      • et al.
      2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
      ,
      • Pfaeffli Dale L.
      • Dobson R.
      • Whittaker R.
      • Maddison R.
      The effectiveness of mobile-health behaviour change interventions for cardiovascular disease self-management: a systematic review.
      • Burke L.E.
      • Ma J.
      • Azar K.M.
      • et al.
      Current science on consumer use of mobile health for cardiovascular disease prevention: a scientific statement from the American Heart Association.
      • Rawstorn J.C.
      • Gant N.
      • Direito A.
      • Beckmann C.
      • Maddison R.
      Telehealth exercise-based cardiac rehabilitation: a systematic review and meta-analysis.
      • Devi R.
      • Singh S.J.
      • Powell J.
      • et al.
      Internet-based interventions for the secondary prevention of coronary heart disease.
      • Adler A.J.
      • Martin N.
      • Mariani J.
      • et al.
      Mobile phone text messaging to improve medication adherence in secondary prevention of cardiovascular disease.
      • Gandhi S.
      • Chen S.
      • Hong L.
      • et al.
      Effect of mobile health interventions on the secondary prevention of cardiovascular disease: systematic review and meta-analysis.
      • Neubeck L.
      • Lowres N.
      • Benjamin E.J.
      • et al.
      The mobile revolution—using smartphone apps to prevent cardiovascular disease.
      • Hivert M.F.
      • Arena R.
      • Forman D.E.
      • et al.
      Medical training to achieve competency in lifestyle counseling: an essential foundation for prevention and treatment of cardiovascular diseases and other chronic medical conditions: a scientific statement from the American Heart Association.
      • Perk J.
      • De Backer G.
      • Gohlke H.
      • et al.
      European guidelines on cardiovascular disease prevention in clinical practice (version 2012): the fifth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
      The RCTs had to be cited in peer-reviewed taskforce guidelines, scientific statements, systematic reviews, and meta-analyses, and/or met the following inclusion criteria: individual digital health interventions for improving blood pressure in populations with elevated CVD risk factors or established CVD; blood pressure was a primary outcome; minimum duration length of 1 month; interventions consisted of mHealth/eHealth protocols that focused on exercise, diet, general lifestyle, and medication adherence; and randomized trials had a specified control group. Trials were only included if they were fully completed, had full length articles, and were written in the English language. Exclusion was based on whether the trial focused on substance abuse or diabetes, or if the intervention was limited to symptom monitoring or telehealth communication between patients and a health care professional, vs an automated program.

      Data collection and analysis

      Selection of reviews

      Two authors (N.S. and B.K.) independently screened all titles and abstracts from the literature search and conducted full text reviews of articles selected from our screening criteria. Any disagreements were resolved by consensus and discussion with the senior author.

      Data extraction

      We extracted and coded data from individual trials according to features noted in Table 1 to evaluate the impact of these recommended features on treatment efficacy and outcome heterogeneity for blood pressure reduction. Complexity of the intervention was defined as simple vs complex: 1-2 vs 3-5 therapeutic components, respectively. Digital interventions were also classified according to whether a clinically organized protocol was noted in the trial methodology. This designation required an explicit reference to using or ordering treatment components according to a formal theory of behaviour change (eg, social cognitive theory,
      • Bandura A.
      Social Foundations of Thought and Action: A Social Cognitive Theory.
      self-efficacy theory,
      • Bandura A.
      Self-efficacy: toward a unifying theory of behavioral change.
      the transtheoretical model of readiness for change,
      • Prochaska J.O.
      • Velicer W.F.
      The transtheoretical model of health behavior change.
      or the health action process approach model
      • Schwarzer R.
      • Lippke S.
      • Luszczynska A.
      Mechanisms of health behavior change in persons with chronic illness or disability: the Health Action Process Approach (HAPA).
      ) or an explicit model of behavioural counselling (eg, cognitive-behavioural therapy [CBT]
      • Beck A.T.
      • Dozois D.J.
      Cognitive therapy: current status and future directions.
      or motivational interviewing [MI]
      • Miller W.R.
      • Rollnick S.
      Motivational Interviewing: Preparing People for Change. 2nd ed.
      ).
      Table 1Trial design features extracted
      Information extractedDescription
      eHealth or mHealth
      • eHealth: use of the internet to improve health and health care delivery
        • Pfaeffli Dale L.
        • Dobson R.
        • Whittaker R.
        • Maddison R.
        The effectiveness of mobile-health behaviour change interventions for cardiovascular disease self-management: a systematic review.
      • mHealth: a subtype of eHealth using mobile electronics (ie, mobile devices, tablets, and wearable devices) for the delivery of health messages and interventions. This can include SMS, MMS, applications, and wireless technology/Bluetooth
      Therapeutic components
      • Patient education: teaching patients about their condition and health self-care behaviours
      • Self-monitoring of symptoms: teaching patients how to monitor and record their symptoms at home
      • Enhanced support: whether the intervention involved real person contact in addition to the digital methods used
      • Intervention tailoring: using specific treatment components that are personalized to the individual
      • Goal setting: setting measurable goals and timeframes
      Level of clinical organization of intervention protocol
      • Unspecified clinical model
      • Behaviour change theory: social cognitive theory, self-efficacy theory, social comparison theory, etc
      • Clinically organized protocol: motivational interviewing, health action process approach theory, Prochaska’s transtheoretical model, etc
        • Prochaska J.O.
        • Velicer W.F.
        The transtheoretical model of health behavior change.
        ,
        • Schwarzer R.
        • Lippke S.
        • Luszczynska A.
        Mechanisms of health behavior change in persons with chronic illness or disability: the Health Action Process Approach (HAPA).
        ,
        • Rollnick S.
        • Miller W.R.
        • Butler C.C.
        • Aloia M.S.
        Motivational interviewing in health care: helping patients change behaviour.

      Data analysis and statistical methods

      RevMan software version 5.3 was used to analyze the data and carry out a meta-analysis.
      The effect size of each trial was calculated using Hedge’s g statistic, in which the difference in reduction of SBP mm Hg between treatment and control groups was divided by the weighted standard deviation. Weighting was estimated using the corresponding sample size in each trial. Data were represented as standardized mean differences (SMDs) and 95% confidence intervals (CI). Hedge’s g criteria were used to determine whether the SMD was small (< 0.2), moderate (0.2-0.5), or large (> 0.5). Trials reporting dramatic outcomes with an SMD ≥ 2.0 were considered outliers and removed from the analysis. The I2 statistic was used to assess heterogeneity. Cut points at 25%, 50%, and 75% marked whether heterogeneity was low, moderate, or high, respectively.
      • Huedo-Medina T.B.
      • Sanchez-Meca J.
      • Marin-Martinez F.
      • Botella J.
      Assessing heterogeneity in meta-analysis: Q statistic or I2 index?.
      Our primary analysis aimed to determine (1) the overall intervention effect of these digital health trials, (2) the intervention effect when categorized into subgroups based on design complexity (number of therapeutic components) and clinical organization, and (3) the interaction effect of design complexity and clinical organization. The objective of our secondary analysis was to determine the impact of controlled vs uncontrolled SBP at baseline on the intervention effect. Uncontrolled BP was defined as a baseline SBP of 140 mm Hg or more and a diastolic blood pressure of 90 mm Hg or more. A random-effects statistical model was selected for the meta-analysis because it allows for variation in the true effect size of each study.
      • Borenstein M.
      • Hedges L.V.
      • Higgins J.P.
      • Rothstein H.R.
      A basic introduction to fixed-effect and random-effects models for meta-analysis.

      Risk of bias assessment

      Risk of bias was assessed using the Cochrane Collaboration tool
      • Higgins J.P.
      • Deeks J.J.
      Selecting studies and collecting data.
      and the Jadad score for study quality.
      • Jadad A.R.
      • Moore R.A.
      • Carroll D.
      • et al.
      Assessing the quality of reports of randomized clinical trials: is blinding necessary?.
      The data collected included the following: method of randomization and allocation concealment; blinding of outcome assessors and participants; and number of participants randomized, excluded and lost to follow-up.

      Results

      Article selection

      The PRISMA flowchart of the trial selection process is presented in Figure 1. We assessed 291 full-text papers, from which 5 guideline papers and 8 systematic reviews met inclusion criteria (Table 2).
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • et al.
      2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      ,
      • Liu S.
      • Dunford S.D.
      • Leung Y.W.
      • et al.
      Reducing blood pressure with Internet-based interventions: a meta-analysis.
      • Beishuizen C.R.
      • Stephan B.C.
      • van Gool W.A.
      • et al.
      Web-based interventions targeting cardiovascular risk factors in middle-aged and older people: a systematic review and meta-analysis.
      • Piepoli M.F.
      • Hoes A.W.
      • Agewall S.
      • et al.
      2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
      ,
      • Pfaeffli Dale L.
      • Dobson R.
      • Whittaker R.
      • Maddison R.
      The effectiveness of mobile-health behaviour change interventions for cardiovascular disease self-management: a systematic review.
      • Burke L.E.
      • Ma J.
      • Azar K.M.
      • et al.
      Current science on consumer use of mobile health for cardiovascular disease prevention: a scientific statement from the American Heart Association.
      • Rawstorn J.C.
      • Gant N.
      • Direito A.
      • Beckmann C.
      • Maddison R.
      Telehealth exercise-based cardiac rehabilitation: a systematic review and meta-analysis.
      • Devi R.
      • Singh S.J.
      • Powell J.
      • et al.
      Internet-based interventions for the secondary prevention of coronary heart disease.
      • Adler A.J.
      • Martin N.
      • Mariani J.
      • et al.
      Mobile phone text messaging to improve medication adherence in secondary prevention of cardiovascular disease.
      • Gandhi S.
      • Chen S.
      • Hong L.
      • et al.
      Effect of mobile health interventions on the secondary prevention of cardiovascular disease: systematic review and meta-analysis.
      • Neubeck L.
      • Lowres N.
      • Benjamin E.J.
      • et al.
      The mobile revolution—using smartphone apps to prevent cardiovascular disease.
      • Hivert M.F.
      • Arena R.
      • Forman D.E.
      • et al.
      Medical training to achieve competency in lifestyle counseling: an essential foundation for prevention and treatment of cardiovascular diseases and other chronic medical conditions: a scientific statement from the American Heart Association.
      • Perk J.
      • De Backer G.
      • Gohlke H.
      • et al.
      European guidelines on cardiovascular disease prevention in clinical practice (version 2012): the fifth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
      A total of 17 trials of digital health for blood pressure reduction were retained for this study (Supplemental Table S1 and S2 for details).
      • Nolan R.P.
      • Feldman R.
      • Dawes M.
      • et al.
      Randomized Controlled Trial of E-Counseling for Hypertension: REACH.
      • Blasco A.
      • Carmona M.
      • Fernandez-lozano I.
      • et al.
      Evaluation of a telemedicine service for the secondary prevention of coronary artery disease.
      • Bove A.A.
      • Homko C.J.
      • Santamore W.P.
      • et al.
      Managing hypertension in urban underserved subjects using telemedicine—a clinical trial.
      • Cicolini G.
      • Simonetti V.
      • Comparcini D.
      • et al.
      Efficacy of a nurse-led email reminder program for cardiovascular prevention risk reduction in hypertensive patients: a randomized controlled trial.
      • Logan A.G.
      • Irvine M.J.
      • McIsaac W.J.
      • et al.
      Effect of home blood pressure telemonitoring with self-care support on uncontrolled systolic hypertension in diabetics.
      • Madsen L.B.
      • Kirkegaard P.
      • Pedersen E.B.
      Blood pressure control during telemonitoring of home blood pressure. A randomized controlled trial during 6 months.
      • Magid D.J.
      • Olson K.L.
      • Billups S.J.
      • et al.
      A pharmacist-led, American Heart Association Heart360 Web-enabled home blood pressure monitoring program.
      • McKinstry B.
      • Hanley J.
      • Wild S.
      • et al.
      Telemonitoring based service redesign for the management of uncontrolled hypertension: multicentre randomised controlled trial.
      • Park M.J.
      • Kim H.S.
      • Kim K.S.
      Cellular phone and Internet-based individual intervention on blood pressure and obesity in obese patients with hypertension.
      • Petrella R.J.
      • Stuckey M.I.
      • Shapiro S.
      • Gill D.P.
      Mobile health, exercise and metabolic risk: a randomized controlled trial.
      • Piette J.D.
      • Datwani H.
      • Gaudioso S.
      • et al.
      Hypertension management using mobile technology and home blood pressure monitoring: results of a randomized trial in two low/middle-income countries.
      • Rifkin D.E.
      • Abdelmalek J.A.
      • Miracle C.M.
      • et al.
      Linking clinic and home: a randomized, controlled clinical effectiveness trial of real-time, wireless blood pressure monitoring for older patients with kidney disease and hypertension.
      • Thiboutot J.
      • Sciamanna C.N.
      • Falkner B.
      • et al.
      Effects of a web-based patient activation intervention to overcome clinical intertia on blood pressure control: cluster randomized controlled trial.
      • Chow C.K.
      • Redfern J.
      • Hillis G.S.
      • et al.
      Effect of lifestyle-focused text messaging on risk factor modification in patients with coronary heart disease: a randomized clinical trial.
      • Park L.G.
      • Howie-Esquivel J.
      • Chung M.L.
      • Dracup K.
      A text messaging intervention to promote medication adherence for patients with coronary heart disease: a randomized controlled trial.
      • Green B.B.
      Effectiveness of home blood pressure monitoring, web communication, and pharmacist care on hypertension control.
      • Nolan R.P.
      • Liu S.
      • Shoemaker J.K.
      • et al.
      Therapeutic benefit of internet-based lifestyle counselling for hypertension.
      • Bobrow K.
      • Farmer A.J.
      • Springer D.
      • et al.
      Mobile phone text messages to support treatment adherence in adults with high blood pressure (SMS-Text Adherence Support [StAR]): a single-blind, randomized trial.
      Figure thumbnail gr1
      Figure 1Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. Literature search and selection process of included studies. RCT, randomized controlled trial.
      Table 2Selected recommended guidelines, scientific statements, and systematic reviews
      Guidelines and scientific statements
      AHA/ACC: Whelton et al. 2018
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • et al.
      2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      Prevention, detection, and management of high blood pressure
      AHA: Burke et al. 2015
      • Burke L.E.
      • Ma J.
      • Azar K.M.
      • et al.
      Current science on consumer use of mobile health for cardiovascular disease prevention: a scientific statement from the American Heart Association.
      Consumer use of mobile health for CVD prevention
      AHA: Hivert et al. 2016
      • Hivert M.F.
      • Arena R.
      • Forman D.E.
      • et al.
      Medical training to achieve competency in lifestyle counseling: an essential foundation for prevention and treatment of cardiovascular diseases and other chronic medical conditions: a scientific statement from the American Heart Association.
      Lifestyle counselling for CVD prevention
      ESC: Piepoli et al. 2016
      • Piepoli M.F.
      • Hoes A.W.
      • Agewall S.
      • et al.
      2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
      CVD prevention in clinical practice
      ESC: Perk et al. 2012
      • Perk J.
      • De Backer G.
      • Gohlke H.
      • et al.
      European guidelines on cardiovascular disease prevention in clinical practice (version 2012): the fifth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
      CVD prevention in clinical practice
      Systematic reviews
      Pfaeffli Dale et al. 2016
      • Pfaeffli Dale L.
      • Dobson R.
      • Whittaker R.
      • Maddison R.
      The effectiveness of mobile-health behaviour change interventions for cardiovascular disease self-management: a systematic review.
      Mobile-health interventions for CVD self-management
      Gandhi et al. 2017
      • Gandhi S.
      • Chen S.
      • Hong L.
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      Quality and risk of bias

      Supplemental Table S2 describes the risk of bias and study quality. Of the 17 trials, 11 were classified as high quality with a Jadad score ≥ 4 out of 5. In the selection bias category, 9 trials were classified as low risk of bias for the method of randomization, and 11 trials were low risk for allocation concealment. Eleven studies were low risk for outcome detection bias, and all studies were low risk for attention bias.

      Intervention details

      The 17 trials in this meta-analysis had a pooled sample of 5780 participants. The mean number of participants per trial was 313 (95% CI: 297-329). The weighted mean percentage of individuals who were prescribed medications was 93% (95% CI: 92.1-93.1) for 11 studies that provided information about medication use. The mean percentage of female participants was 33% (95% CI: 32.2-33.3). The average intervention duration was 7.7 months, with 7 trials at 12 months, 6 trials at 6 months, and 4 trials at less than 6 months.

      Intervention effects

      Figure 2 indicates that our pool of 17 trials had a statistically significant therapeutic effect for blood pressure reduction with moderate heterogeneity. There was a weighted mean reduction in SBP of −7.3 mm Hg (95% CI: −7.0 to −7.5) for intervention groups, compared with −3.6 mm Hg (95% CI: −3.9 to −3.4) for controls.
      Figure thumbnail gr2
      Figure 2Intervention effects for systolic blood pressure reduction. CI, confidence interval; IV, inverse variance; SE, standard error.

      Design complexity

      Figure 3 indicates a low-moderate SMD for the treatment outcome of trials with a simple design (n = 4) with 1-2 intervention components, vs a complex design (n = 13) with 3-5 components. Heterogeneity was significant only for trials with a complex design.
      Figure thumbnail gr3
      Figure 3Impact of design complexity on the intervention effect. Forest plot displaying the main effect of a simple vs complex intervention design for systolic blood pressure outcomes. CI, confidence interval; IV, inverse variance; SE, standard error.

      Clinical organization

      Only 4 of the 17 (25%) trials in our review noted that a theory of behaviour change or a model of behavioural counselling was used to organize behaviour change components in the intervention protocol. Figure 4 indicates that these trials had a moderate-high SMD with low-moderate heterogeneity. In contrast, trials that did not specify whether the protocol was organized by a behaviour change theory or a counselling model had a low SMD and moderate-high outcome heterogeneity. A comparison of both groups of trials indicated that the SMD was significantly greater among trials with a specified model of behaviour change or counselling (Fig. 4).
      Figure thumbnail gr5
      Figure 5Impact of interaction between intervention design for trials without a theoretical framework on the intervention effect. Forest plot displaying the interaction effect of design complexity for trials not organized by a clinical theoretical framework. CI, confidence interval; IV, inverse variance; SE, standard error.
      Figure thumbnail gr4
      Figure 4Impact of clinical organization on the intervention effect. Forest plot displaying the main effect of trials with vs without a theoretical framework on systolic blood pressure outcomes. CI, confidence interval; IV, inverse variance; SE, standard error.

      Interaction effect: protocol without a specified theoretical framework

      Trials that did not specify whether the protocol was organized by a model of behaviour change or counselling were associated with a low-moderate SMD, regardless of whether the intervention had a simple or complex intervention design. Heterogeneity (I2) was higher in trials that used multiple therapeutic components (Fig. 5).

      Interaction effect: protocol with a specified theoretical framework

      Trials that specified that the intervention protocol was organized by a behaviour change theory or a counselling model solely used a complex design with multiple therapeutic components. These trials demonstrated a moderate-high SMD with low heterogeneity (Fig. 6), which translated to a reduction in the SBP of −4.8 mm Hg for digital counselling (95% CI: −5.09 to −4.57) vs −1.4 mm Hg (95% CI: −1.89 to −0.99) for control.
      Figure thumbnail gr6
      Figure 6Impact of interaction between intervention design for trials with a theoretical framework on the intervention effect. Forest plot displaying the interaction effect of design complexity for trials organized by a clinical theoretical framework. CI, confidence interval; IV, inverse variance; SE, standard error.

      Uncontrolled and controlled BP at baseline

      Figure 7 presents a subanalysis of SBP outcomes based on uncontrolled vs controlled BP at baseline. A moderate SMD for treatment outcome was demonstrated among patients with uncontrolled BP, compared with a low SMD in patients with controlled BP. This outcome was equivalent to a weighted mean SBP reduction of −10.95 mm Hg (95% CI: −10.6 to 11.3) in the uncontrolled BP group, vs −2.8 mm Hg (95% CI: −3.07 to −2.6) in the controlled BP group.
      Figure thumbnail gr7
      Figure 7Impact of baseline population SBP on the intervention effect. CI, confidence interval; IV, inverse variance; SBP, systolic blood pressure; SE, standard error.

      Discussion

      This meta-analysis examined the efficacy and outcome heterogeneity of clinical trials that have helped to shape the field of digitally based behavioural counselling for blood pressure reduction, by virtue of their contribution to guideline and policy statements by societies of cardiovascular health, and to major systematic reviews. This review was distinct in highlighting how outcomes were associated with key features of the intervention protocol.
      There are 3 main findings of interest. First, antihypertensive therapy was included as part of the intervention among 93% of trials. Therefore, the present sample of clinical trials demonstrated that digital counselling optimized the efficacy of antihypertensive medical therapy. The magnitude of improvement was clinically meaningful insofar as there was a 2-fold incremental reduction in SBP for digital interventions (−7.3 mm Hg) relative to controls (−3.7 mm Hg). This outcome was pronounced in trials that recruited patients with uncontrolled vs controlled blood pressure. The observed therapeutic benefit of digital counselling appears to be robust under conditions of a rigorous trial design. For example, the Randomized Controlled Trial of e-Counseling for Hypertension (REACH) trial reported a similar therapeutic benefit for digital counselling vs control in a 12-month double-blind RCT where 83% of the sample was prescribed antihypertensive medications.
      • Nolan R.P.
      • Feldman R.
      • Dawes M.
      • et al.
      Randomized Controlled Trial of E-Counseling for Hypertension: REACH.
      The SBP reduction was −10.1 mm Hg for the digital intervention, vs −6.0 mm Hg for control.
      • Nolan R.P.
      • Feldman R.
      • Dawes M.
      • et al.
      Randomized Controlled Trial of E-Counseling for Hypertension: REACH.
      At the same time, it is noteworthy that the problem of heterogeneity in treatment outcome persists even in digital trials that could be considered exemplary, given their citations in task force guideline statements for managing hypertension.
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • et al.
      2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      ,
      • Piepoli M.F.
      • Hoes A.W.
      • Agewall S.
      • et al.
      2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
      ,
      • Burke L.E.
      • Ma J.
      • Azar K.M.
      • et al.
      Current science on consumer use of mobile health for cardiovascular disease prevention: a scientific statement from the American Heart Association.
      ,
      • Hivert M.F.
      • Arena R.
      • Forman D.E.
      • et al.
      Medical training to achieve competency in lifestyle counseling: an essential foundation for prevention and treatment of cardiovascular diseases and other chronic medical conditions: a scientific statement from the American Heart Association.
      ,
      • Perk J.
      • De Backer G.
      • Gohlke H.
      • et al.
      European guidelines on cardiovascular disease prevention in clinical practice (version 2012): the fifth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
      This underscores a major challenge for the evolving field of digitally based behavioural counselling for blood pressure reduction, which is to use standardized protocols that can improve the replication of therapeutic outcomes vs optimizing treatment efficacy alone.
      The second finding of interest is that digital interventions demonstrated greater therapeutic benefit for SBP reduction when the protocol was designed according to an explicit theory of behaviour change or model of behavioural counselling. These trials were associated with a moderate standardized treatment effect and reduced heterogeneity in clinical outcomes. It is reasonable to expect that the quality of digital health interventions for CVD risk reduction would be improved if the standard for reporting clinical trials included specifying how an evidence-based model of care was operationalized in the digital protocol. Interestingly, clinical trial reporting checklists such as the Consolidated Standards of Reporting Trials of Electronic and Mobile HEalth Applications and onLine TeleHealth (CONSORT-EHEALTH) were developed to improve the quality of digital health research by standardizing the reporting of critical features in the trial design and methodology.
      • Eysenbach G.
      CONSORT-EHEALTH Group
      CONSORT-EHEALTH: improving and standardizing evaluation reports of web-based and mobile health interventions.
      The identification of an explicit model of behaviour change or behavioural counselling is currently omitted from the CONSORT-EHEALTH checklist. Therefore, the present findings may help to correct this oversight and thereby add to recent collaborative efforts to improve the evolving digital health field.
      • Moller A.C.
      • Merchant G.
      • Conroy D.E.
      • et al.
      Applying and advancing behavior change theories and techniques in the context of a digital health revolution: proposals for more effectively realizing untapped potential.
      The third major finding of this study also concerns the subset of trials where the protocol was organized by an explicit behaviour change theory or a behavioural counselling model. These trials solely used a complex (vs simple) design for the intervention, which included multiple components such as goal setting, patient education, and monitoring of symptoms or self-care behaviours. The use of multiple therapeutic components in a digital intervention strategy for hypertension is likely required to appropriately adapt and improve on the foundational models of evidence-based behavioural counselling, such as CBT
      • Hadjistavropoulos H.D.
      • Schneider L.H.
      • Klassen K.
      • Dear B.F.
      • Titov N.
      Development and evaluation of a scale assessing therapist fidelity to guidelines for delivering therapist-assisted Internet-delivered cognitive behaviour therapy.
      or MI.
      • Moyers T.B.
      • Rowell L.N.
      • Manuel J.K.
      • Ernst D.
      • Houck J.M.
      The Motivational Interviewing Treatment Integrity Code (MITI 4): rationale, preliminary reliability and validity.
      This is suggested by the current practice of using complex, multicomponent coding schemas of behavioural counselling strategies
      • Michie S.
      • Prestwich A.
      Are interventions theory-based? Development of a theory coding scheme.
      to evaluate the fidelity of behavioural interventions for CBT
      • Hadjistavropoulos H.D.
      • Schneider L.H.
      • Klassen K.
      • Dear B.F.
      • Titov N.
      Development and evaluation of a scale assessing therapist fidelity to guidelines for delivering therapist-assisted Internet-delivered cognitive behaviour therapy.
      and MI.
      • Moyers T.B.
      • Rowell L.N.
      • Manuel J.K.
      • Ernst D.
      • Houck J.M.
      The Motivational Interviewing Treatment Integrity Code (MITI 4): rationale, preliminary reliability and validity.
      Moreover, meta-analytic evidence from clinical trials of physical exercise among individuals with type 2 diabetes indicates that therapeutic outcomes are improved by the use of a multicomponent counselling protocol with ≥ 10 behaviour change techniques, and by the use of an organizing theory of behaviour change.
      • Avery L.
      • Flynn D.
      • van Wersch A.
      • Sniehotta F.F.
      • Trenell M.I.
      Changing physical activity behavior in type 2 diabetes: a systematic review and meta-analysis of behavioral interventions.
      There are potential economic barriers to the successful deployment of a digital counselling strategy that uses an evidence-based model of behavioural counselling to organize a complex set of behaviour change components to promote cardiovascular health. Growth in digital health has been driven primarily by an increase in the use of mobile or smartphone devices,
      • Hitlin P.
      Internet, social media use and device ownership in U.S. have plateaued after years of growth
      FACTANK: News in the Numbers.
      which require a streamlined design for the intervention and user interface. This growth trend is projected to at least 2024, with a compound annual growth rate of over 25%.
      • Ugalmugale S.
      Digital Health Market Size By Technology (Telehealthcare, mHealth, Health Analytics, Digital Health Systems), Industry Analysis Report, Regional Outlook (U.S., Canada, Germany, UK, France, Spain, Italy, Russia, Poland, Japan, China, India, Australia, Brazil, Mexico, South Africa), Application Potential, Competitive Market Share & Forecast, 2018-2024.
      Of note is that this economic activity has been characterized by “short-termism,” in which there is a preference for short-term investments in innovations that require minor modifications to existing technology.
      • Sampson R.
      • Shi Y.
      Is Corporate Short-Termism on the Rise in the U.S.?.
      It may be more challenging to attract industry partnerships in this economic climate if the clinical science agenda for digital health promotion deviates from the popular array of streamlined mobile-based interventions, especially if this requires a long-term investment strategy that poses greater risk on the investment return. The challenge of ensuring that developments in clinical science keep pace with the rapid growth of digital health technology is an issue that has been addressed by task force groups from cardiovascular health societies
      • Bhavnani S.P.
      • Parakh K.
      • Atreja A.
      • et al.
      2017 Roadmap for Innovation-ACC Health Policy statement on healthcare transformation in the era of digital health, big data, and precision health: a report of the American College of Cardiology Task Force on health policy statements and systems of care.
      and networks of collaborating scientists.
      • Moller A.C.
      • Merchant G.
      • Conroy D.E.
      • et al.
      Applying and advancing behavior change theories and techniques in the context of a digital health revolution: proposals for more effectively realizing untapped potential.
      It promises to be an important issue to monitor as an evidence-based digital health strategy evolves for blood pressure management and cardiovascular health promotion.

      Limitations

      A limitation to our study is that it was not possible to assess whether there was an independent association between SBP reduction and specific therapeutic components, or individual models of behaviour change or behavioural counselling. A multivariable meta-regression was attempted, but significant heterogeneity precluded us from interpreting the results. It is a priority for future studies to evaluate whether therapeutic outcomes are improved with specific features of digital health interventions. Our calculation of an SMD in SBP outcome for each trial was based on an intention-to-treat analysis, when possible. There were 5 trials that failed to use this approach; therefore, our analysis was based on the reported per-protocol analysis in each case. It is also important to acknowledge that we classified trials in our review as failing to specify a clinical framework for the digital counselling protocol based on the available evidence. We searched each paper for references to protocol papers or other publications in an effort to find additional protocol information for trials that we classified as failing to specify a clinical framework for the protocol. In the absence of locating an appropriate citation, we were obliged to base our classification schema on the published information at hand. It is possible that those trials may have referenced the use of a behaviour change theory or a model of behavioural counselling in a publication that we could not locate. As noted above, our priority was to identify and evaluate clinical trials that have helped to shape the development of the digital health field for hypertension, by virtue of their citation in guideline papers by international cardiovascular societies as well as major systematic reviews. We also conducted a literature search for individual trials that were not cited in these reviews, and which were published between January 2017 and January 2019. This additional literature search was performed to update and complement the trials included in the taskforce guidelines, scientific statements, and systematic reviews that had been published as far back as 2012.

      Conclusion

      Digital health interventions optimize the efficacy of medical therapy with a 2-fold incremental reduction in blood pressure in comparison with control interventions. These interventions are likely to be more efficacious and replicable when an explicit model of behaviour change or behavioural counselling is used to organize the protocol design, which is consistent with guidelines for clinic-based interventions.
      • Hivert M.F.
      • Arena R.
      • Forman D.E.
      • et al.
      Medical training to achieve competency in lifestyle counseling: an essential foundation for prevention and treatment of cardiovascular diseases and other chronic medical conditions: a scientific statement from the American Heart Association.
      ,
      • Riegel B.
      • Moser D.K.
      • Buck H.G.
      • et al.
      Self-care for the prevention and management of cardiovascular disease and stroke: a scientific statement for healthcare professionals from the American Heart Association.
      Given that digital health applications are projected to grow at an accelerated rate to at least 2024, there is a great opportunity to promote a disruptive change where clinical science and digital technology play equal roles in reciprocally transforming the field of digitally based cardiovascular health promotion.

      Acknowledgements

      We are grateful to Julia Wong and Carol Yick for their assistance in the preparation of this paper.

      Funding Sources

      There are no funding sources to declare.

      Disclosures

      The authors have no conflicts of interest to disclose.

      Supplementary Material

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