Participants' views of ultra-low dose combination therapy for high blood pressure: a mixed-methods study from the QUARTET trial.

Single-pill combination therapy containing four quarter-dose medications for high blood pressure improves BP control compared to monotherapy, however patient-reported acceptance of the quadpill as a treatment strategy remains undescribed. We collected within-trial feedback and interviewed participants from the quadruple ultra-low-dose treatment for hypertension (QUARTET) trial to characterise patient attitudes to this intervention. All trial participants were asked about ease and preference for the quadpill and provided an opportunity to give further comments on the trial at 12 weeks (trial primary endpoint) and 52 weeks extended follow-up. Separately, we used purposive and quota sampling for the semi-structured telephone interviews, with the resultant verbatim transcripts analysed using an inductive thematic analysis approach. Themes were re-evaluated after each successive interview, and at suspected data saturation, an additional interview conducted for confirmation. At 12 weeks follow-up, 502 of 591 (85%) participants responded to acceptability questions, and 359 of 417 (86%) responded at week 52. Most reported the trial capsule easy or very easy to take. From eight sites, 16 participants were interviewed between 5 August 2020 and 19 November 2020. All described a positive experience, preferred once-daily morning dosing and found routine facilitated adherence. Participants valued individual responsibility for adherence, and involvement of the general practitioner in blood-pressure management. Most reported capsule size did not deter adherence but desired a smaller capsule. Participants described a preference for minimising number and dosage of medications, reduced capsule size, and once-daily morning dosing. These findings suggest a preference for single-pill combination therapy for blood pressure lowering.

Therapeutic Inertia With Initial Low-Dose Quadruple Combination Therapy for Hypertension: Results From the QUARTET Trial.

BACKGROUND: Low-dose combinations are a promising intervention for improving blood pressure (BP) control but their effects on therapeutic inertia are uncertain. METHODS: Analysis of 591 patients randomized to an ultra-low-dose quadruple pill or initial monotherapy. The episode of therapeutic inertia was defined as a patient visit with a BP of >140/90 mm Hg without intensification of antihypertensive treatment. We compared the frequency of therapeutic inertia episodes between Quadpill and initial monotherapy as a proportion of the total population (intention-to-treat analysis with the denominator being all participants randomized) and as a proportion of people with uncontrolled BP (with the denominator being participants with uncontrolled BP). RESULTS: Therapeutic inertia occurred in fewer participants randomized to Quadpill compared with monotherapy. For example, among the 390 participants with a 6-month follow-up, therapeutic inertia according to unattended BP was 21/192 (11%) versus 45/192 (23%), P=0.002. There were similar rates of therapeutic inertia among those with uncontrolled unattended BP in each group (all P>0.4). Consistent observations were seen with the use of attended office BP measures. The major determinants of not intensifying treatment during follow-up were BP readings that were close to target and large improvements in BP compared with the previous visit. CONCLUSIONS: Among all treated individuals, low-dose Quadpill reduced the number of therapeutic inertia episodes compared with initial monotherapy. After the first follow-up visit, most high BP values did not lead to treatment intensification in both groups. Education is needed about the importance of treatment intensification despite a significant improvement in BP or BP being close to target. REGISTRATION: URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12616001144404; Unique identifier: ACTRN12616001144404.

Utilisation of Chronic Disease and Mental Health Management Services and Cardioprotective Medication Prescriptions in Primary Care for Patients With Cardiovascular Diseases and Cancer: A Cross-Sectional Study.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among cancer survivors. Mental health is considered an important risk factor affecting the treatment of cardiovascular disease. However, little is known about the use of secondary prevention strategies for CVD in patients with both cancer and CVD. This study aimed to compare the utilisation of primary care chronic disease management plans, mental health care and guideline-indicated cardioprotective medications among CVD patients with and without cancer. METHODS: Retrospective cross-sectional study utilising clinical data of patients with CVD from 50 Australian primary care practices. Outcomes included the use of chronic disease management plans, mental health care, guideline-indicated cardioprotective medications and influenza vaccination. Logistic regression, accounting for demographic and clinical covariates and clustering effects by practices, was used to compare the two groups. RESULTS: Of the 15,040 patients with CVD, 1,486 patients (9.9%) concurrently had cancer. Patients with cancer, compared to those without, were older (77.6 vs 71.8 years, p<0.001), more likely to drink alcohol (62.6% vs 55.7%, p<0.001), have lower systolic (130.3±17.8 vs 132.5±21.1 mmHg, p<0.001) and diastolic (72.2±11 vs 75.3±34 mmHg, p<0.001) blood pressure. Although suboptimal for both groups, patients with cancer were significantly more likely to have general practice management plans (GPMPs) (51.4% vs 43.2%, p<0.001), coordination of team care arrangements (TCAs) (46.2% vs 37.0%, p<0.001), have a review of either GPMP or TCA (42.8% vs 34.7%, p<0.001), have a mental health treatment consultation (15.4% vs 10.5%, p=0.004) and be prescribed blood pressure-lowering medications (70.1% vs 66.0%, p=0.002). However, there were no statistical differences in the prescription of lipid-lowering or antiplatelet medications. After adjustments for covariates and multiple testing, patients with cancer did not show a difference in GPMPs, TCAs, and a review of either, but were more likely to receive mental health treatment consultations than those without cancer (odds ratio 1.76; 95% confidence interval 1.42-2.19). CONCLUSIONS: Less than half of patients with CVD had a GPMP, TCA or review of either. Although those patients with cancer were more likely to receive these interventions, still around half the patients did not. Medicare-funded GPMPs, TCAs and a review of either GPMP or TCA were underutilised, and future studies should seek to identify ways of improving access to these services.

Long-Term Pattern and Associated Costs of Re-hospitalisations in Patients After Index Atrial Fibrillation Admission in Western Australia, 2011-2017.

AIMS: This study aimed to determine total and cardiovascular-specific re-hospitalisation patterns and associated costs within 2 years of index atrial fibrillation (AF) admission in Western Australia (WA). METHOD: Patients aged 25-94 years, surviving an index (first-in-period) AF hospitalisation (principal diagnosis) from 2011 to 2015 were identified from WA-linked administrative data and followed for 2 years. Person-level hospitalisation costs ($ Australian dollar) were computed using the Australian Refined Diagnosis Related Groups and presented as median with first and third quartile costs. RESULTS: The cohort comprised 17,080 patients, 59.0% men, mean age 69.6±13.3 (standard deviation) years, and 59.0% had a CHA2DS2-VA (one point for congestive heart failure, hypertension, diabetes mellitus, vascular disease or age 65-74 years; two points for prior stroke/transient ischaemic attack or age ≥75 years) score of 2 or more. Within 2 years, 13,776 patients (80.6%) were readmitted with median of 2 (1-4) readmissions. Among total all-cause readmissions (n=54,240), 40.1% were emergent and 36.6% were cardiovascular-related, led by AF (19.5%), coronary events (5.8%), and heart failure (4.2%). The median index AF admission cost was $3,264 ($2,899-$7,649) while cardiovascular readmission costs were higher, particularly stroke ($10,732 [$4,179-23,390]), AF ablation ($7,884 [$5,283-$8,878]), and heart failure ($6,759 [$6,081-$13,146]). Average readmission costs over 2 years per person increased by $4,746 (95% confidence interval [CI] $4,459-$5,033) per unit increase in baseline CHA2DS2-VA score. The average 2-year hospitalisation costs per patient, including index admission, was $27,820 (95% CI $27,308-$28,333) and total WA costs were $475.2 million between 2011 and 2017. CONCLUSIONS: Patients after index AF hospitalisation have a high risk of cardiovascular and other readmissions with considerable healthcare cost implications. Readmission costs increased progressively with baseline CHA2DS2-VA score. Better integrated management of AF and coexistent comorbidities is likely key to reducing readmissions and associated costs.

Cost-effectiveness of ultra-low-dose quadruple combination therapy for high blood pressure.

OBJECTIVE: To determine the cost-effectiveness and cost-utility of a quadpill containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg and bisoprolol 2.5 mg in comparison with irbesartan 150 mg for people with hypertension who are either untreated or receiving monotherapy. METHODS: We conducted a within-trial and modelled economic evaluation of the Quadruple UltrA-low-dose tReaTment for hypErTension trial. The analysis was preplanned, and medications and health service use captured during the trial. The main outcomes were incremental cost-effectiveness ratios (ICERs) for cost per mm Hg systolic blood pressure (BP) reduction at 3 months, and modelled cost per quality-adjusted life year (QALY) over a lifetime. RESULTS: The within-trial analysis showed no clear difference in cost per mm Hg BP lowering between randomised treatments at 3 months ($A10 (95% uncertainty interval (UI) $A -18 to $A37) per mm Hg per person) for quadpill versus monotherapy. The modelled cost-utility over a lifetime projected a mean incremental cost of $A265 (95% UI $A166 to $A357) and a mean 0.02 QALYs gained (95% UI 0.01 to 0.03) per person with quadpill therapy compared with monotherapy. Quadpill therapy was cost-effective in the base case (ICER of $A14 006 per QALY), and the result was sensitive to the quadpill cost in one-way sensitivity analysis. CONCLUSIONS: Quadpill in comparison with monotherapy is comparably cost-effective for short-term BP lowering. In the long-term, quadpill therapy is likely to be cost-effective. TRIAL REGISTRATION NUMBER: ANZCTRN12616001144404.

Transforming blood pressure control in primary care through a novel remote decision support strategy based on wearable blood pressure monitoring: The NEXTGEN-BP randomized trial protocol.

BACKGROUND: Despite high blood pressure being the leading preventable risk factor for death, only 1 in 3 patients achieve target blood pressure control. Key contributors to this problem are clinical inertia and uncertainties in relying on clinic blood pressure measurements to make treatment decisions. METHODS: The NEXTGEN-BP open-label, multicenter, randomized controlled trial will investigate the efficacy, safety, acceptability and cost-effectiveness of a wearable blood pressure monitor-based care strategy for the treatment of hypertension, compared to usual care, in lowering clinic blood pressure over 12 months. NEXTGEN-BP will enroll 600 adults with high blood pressure, treated with 0 to 2 antihypertensive medications. Participants attending primary care practices in Australia will be randomized 1:1 to the intervention of a wearable-based remote care strategy or to usual care. Participants in the intervention arm will undergo continuous blood pressure monitoring using a wrist-wearable cuffless device (Aktiia, Switzerland) and participate in 2 telehealth consultations with their primary care practitioner (general practitioner [GP]) at months 1 and 2. Antihypertensive medication will be up-titrated by the primary care practitioner at the time of telehealth consults should the percentage of daytime blood pressure at target over the past week be <90%, if clinically tolerated. Participants in the usual care arm will have primary care consultations according to usual practice. The primary outcome is the difference between intervention and control in change in clinic systolic blood pressure from baseline to 12 months. Secondary outcomes will be assessed at month 3 and month 12, and include acceptability to patients and practitioners, cost-effectiveness, safety, medication adherence and patient engagement. CONCLUSIONS: NEXTGEN-BP will provide evidence for the effectiveness and safety of a new paradigm of wearable cuffless monitoring in the management of high blood pressure in primary care. TRIAL REGISTRATION: ACTRN12622001583730.

Age-Related Variation in the Provision of Primary Care Services and Medication Prescriptions for Patients with Cardiovascular Disease.

As population aging progresses, demands of patients with cardiovascular diseases (CVD) on the primary care services is inevitably increased. However, the utilisation of primary care services across varying age groups is unknown. The study aims to explore age-related variations in provision of chronic disease management plans, mental health care, guideline-indicated cardiovascular medications and influenza vaccination among patients with CVD over differing ages presenting to primary care. Data for patients with CVD were extracted from 50 Australian general practices. Logistic regression, accounting for covariates and clustering effects by practices, was used for statistical analysis. Of the 14,602 patients with CVD (mean age, 72.5 years), patients aged 65-74, 75-84 and ≥85 years were significantly more likely to have a GP management plan prepared (adjusted odds ratio (aOR): 1.6, 1.88 and 1.55, respectively, p < 0.05), have a formal team care arrangement (aOR: 1.49, 1.8, 1.65, respectively, p < 0.05) and have a review of either (aOR: 1.63, 2.09, 1.93, respectively, p < 0.05) than those < 65 years. Patients aged ≥ 65 years were more likely to be prescribed blood-pressure-lowering medications and to be vaccinated for influenza. However, the adjusted odds of being prescribed lipid-lowering and antiplatelet medications and receiving mental health care were significantly lowest among patients ≥ 85 years. There are age-related variations in provision of primary care services and pharmacological therapy. GPs are targeting care plans to older people who are more likely to have long-term conditions and complex needs.

Data-driven quality improvement program to prevent hospitalisation and improve care of people living with coronary heart disease: Protocol for a process evaluation.

BACKGROUND: Practice-level quality improvement initiatives using rapidly advancing technology offers a multidimensional approach to reduce cardiovascular disease burden. For the "QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease" (QUEL) cluster randomised controlled trial, a 12-month quality improvement intervention was designed for primary care practices to use data and implement progressive changes using "Plan, Do, Study, Act" cycles within their practices with training in a series of interactive workshops. This protocol aims to describe the systematic methods to conduct a process evaluation of the data-driven intervention within the QUEL study. METHODS: A mixed-method approach will be used to conduct the evaluation. Quantitative data collected throughout the intervention period, via surveys and intervention materials, will be used to (1) identify the key elements of the intervention and how, for whom and in what context it was effective; (2) determine if the intervention is delivered as intended; and (3) describe practice engagement, commitment and capacity associated with various intervention components. Qualitative data, collected via semi-structured interviews and open-ended questions, will be used to gather in-depth understanding of the (1) satisfaction, utility, barriers and enablers; (2) acceptability, uptake and feasibility, and (3) effect of the COVID-19 pandemic on the implementation of the intervention. CONCLUSION: Findings from the evaluation will provide new knowledge on the implementation of a complex, multi-component intervention at practice-level using their own electronic patient data to enhance secondary prevention of cardiovascular disease. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134.

Adherence Clubs to Improve Hypertension Management in Nigeria: Clubmeds, a Feasibility Study.

Background: Hypertension control remains a significant challenge in reducing the cardiovascular disease burden worldwide. Community peer-support groups have been identified as a promising strategy to improve medication adherence and blood pressure (BP) control. Objectives: The study aimed to evaluate the feasibility and impact of adherence clubs to improve BP control in Southeast Nigeria. Methods: This was a mixed-methods research involving a formative (pre-implementation) research, pilot study and process evaluation. Hypertensive patients in two communities were recruited into peer-support adherence clubs under the leadership of role-model patients to motivate and facilitate medication adherence, BP monitoring, and monthly medication delivery for six months. The primary outcome was medication adherence measured using visual analogue scale (VAS), with BP level at six months as a key secondary outcome. Results: We recruited a total of 104 participants. The mean age was 56.8 (SD-10.7) years, 72 (69.2%) were women, mean BP was 146.7 (SD-20.1)/86.9 (SD-11.2) mmHg, and the mean percentage of medication adherence on the VAS was 41.4% (SD-11.9%). At six months, 67 patients were assessed; self-reported adherence on the VAS increased to 57.3% (SD-25.3%) (mean difference between baseline and follow-up of 15.5%, p < 0.0001), while the mean BP decreased to 132.3 (SD-22.0)/82.9 (SD-12.2) mmHg (mean difference of 13.0 mmHg in systolic BP, p < 0.0001 and of 3.6 mmHg in diastolic BP, p = 0.02). Five in-depth interviews and four focus groups discussions were conducted as part of the qualitative analyses of the study. The participants saw hypertension as a big issue, with many unaware of the diagnosis, and they accepted the CLUBMEDS differential service delivery (DSD) model concept in hypertension. Conclusions: The study demonstrates that the implementation of adherence clubs for hypertension control is feasible and led to a statistically significant and clinically meaningful improvement in self-reported medication adherence, resulting in BP reduction. Upscaling the intervention may be needed to confirm these findings.

Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial.

BACKGROUND: Treatment inertia is a recognised barrier to blood pressure control, and simpler, more effective treatment strategies are needed. We hypothesised that a hypertension management strategy starting with a single pill containing ultra-low-dose quadruple combination therapy would be more effective than a strategy of starting with monotherapy. METHODS: QUARTET was a multicentre, double-blind, parallel-group, randomised, phase 3 trial among Australian adults (≥18 years) with hypertension, who were untreated or receiving monotherapy. Participants were randomly assigned to either treatment, that started with the quadpill (containing irbesartan at 37·5 mg, amlodipine at 1·25 mg, indapamide at 0·625 mg, and bisoprolol at 2·5 mg) or an indistinguishable monotherapy control (irbesartan 150 mg). If blood pressure was not at target, additional medications could be added in both groups, starting with amlodipine at 5 mg. Participants were randomly assigned using an online central randomisation service. There was a 1:1 allocation, stratified by site. Allocation was masked to all participants and study team members (including investigators and those assessing outcomes) except the manufacturer of the investigational product and one unmasked statistician. The primary outcome was difference in unattended office systolic blood pressure at 12 weeks. Secondary outcomes included blood pressure control (standard office blood pressure <140/90 mm Hg), safety, and tolerability. A subgroup continued randomly assigned allocation to 12 months to assess long-term effects. Analyses were per intention to treat. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry, ACTRN12616001144404, and is now complete. FINDINGS: From June 8, 2017, to Aug 31, 2020, 591 participants were recruited, with 743 assessed for eligibility, 152 ineligible or declined, 300 participants randomly assigned to intervention of initial quadpill treatment, and 291 to control of initial standard dose monotherapy treatment. The mean age of the 591 participants was 59 years (SD 12); 356 (60%) were male and 235 (40%) were female; 483 (82%) were White, 70 (12%) were Asian, and 38 (6%) reported as other ethnicity; and baseline mean unattended office blood pressure was 141 mm Hg (SD 13)/85 mm Hg (SD 10). By 12 weeks, 44 (15%) of 300 participants had additional blood pressure medications in the intervention group compared with 115 (40%) of 291 participants in the control group. Systolic blood pressure was lower by 6·9 mm Hg (95% CI 4·9-8·9; p<0·0001) and blood pressure control rates were higher in the intervention group (76%) versus control group (58%; relative risk [RR] 1·30, 95% CI 1·15-1·47; p<0·0001). There was no difference in adverse event-related treatment withdrawals at 12 weeks (intervention 4·0% vs control 2·4%; p=0·27). Among the 417 patients who continued, uptitration occurred more frequently among control participants than intervention participants (p<0·0001). However, at 52 weeks mean unattended systolic blood pressure remained lower by 7·7 mm Hg (95% CI 5·2-10·3) and blood pressure control rates higher in the intervention group (81%) versus control group (62%; RR 1·32, 95% CI 1·16-1·50). In all randomly assigned participants up to 12 weeks, there were seven (3%) serious adverse events in the intervention group and three (1%) serious adverse events in the control group. INTERPRETATION: A strategy with early treatment of a fixed-dose quadruple quarter-dose combination achieved and maintained greater blood pressure lowering compared with the common strategy of starting monotherapy. This trial demonstrated the efficacy, tolerability, and simplicity of a quadpill-based strategy. FUNDING: National Health and Medical Research Council, Australia.

Gender Comparison of Receipt of Government-Funded Health Services and Medication Prescriptions for the Management of Patients With Cardiovascular Disease in Primary Care.

BACKGROUND: Cardiovascular disease (CVD) and risk factors remains a major burden in terms of disease, disability, and death in the Australian population and mental health is considered as an important risk factor affecting cardiovascular disease. A multidisciplinary collaborative approach in primary care is required to ensure an optimal outcome for managing cardiovascular patients with mental health issues. Medicare introduced numerous primary care health services and medications that are subsidised by the Australian government in order to provide a more structured approach to reduce and manage CVD. However, the utilisation of these services nor gender comparison for CVD management in primary care has been explored. Therefore, the aim is to compare the provision of subsidised chronic disease management plans (CDMPs), mental health care and prescription of guideline-indicated medications to men and women with CVD in primary care practices for secondary prevention. METHODS: De-identified data for all active patients with CVD were extracted from 50 Australian primary care practices. Outcomes included the frequency of receipt of CDMPs, mental health care and prescription of evidence-based medications. Analyses adjusted for demography and clinical characteristics, stratified by gender, were performed using logistic regression and accounted for clustering effects by practices. RESULTS: Data for 14,601 patients with CVD (39.4% women) were collected. The odds of receiving the CDMPs was significantly greater amongst women than men (preparation of general practice management plan [GPMP]: (46% vs 43%; adjusted OR [95% CI]: 1.22 [1.12, 1.34]). Women were more likely to have diagnosed with mental health issues (32% vs 20%, p<0.0001), however, the adjusted odds of men and women receiving any government-subsidised mental health care were similar. Women were less often prescribed blood pressure, lipid-lowering and antiplatelet medications. After adjustment, only an antiplatelet medication or agent was less likely to be prescribed to women than men (44% vs 51%; adjusted OR [95% CI]: 0.84 [0.76, 0.94]). CONCLUSION: Women were more likely to receive CDMPs but less likely to receive antiplatelet medications than men, no gender difference was observed in the receipt of mental health care. However, the receipt of the CDMPs and the mental health treatment consultations were suboptimal and better use of these existing services could improve ongoing CVD management.

Ultra-low-dose quadruple combination blood pressure-lowering therapy in patients with hypertension: The QUARTET randomized controlled trial protocol.

High blood pressure is the leading cause of preventable morbidity and mortality globally. Many patients remain on single-drug treatment with poor control, although guidelines recognize that most require combination therapy for blood pressure control. Our hypothesis is that a single-pill combination of 4 blood pressure-lowering agents each at a quarter dose may provide a simple, safe, and effective blood pressure-lowering solution which may also improve long-term adherence. The Quadruple UltrA-low-dose tReaTment for hypErTension (QUARTET) double-blind, active-controlled, randomized clinical trial will examine whether ultra-low-dose quadruple combination therapy is more effective than guideline-recommended standard care in lowering blood pressure. QUARTET will enroll 650 participants with high blood pressure either on no treatment or on monotherapy. Participants will be randomized 1:1 and allocated to intervention therapy of a single pill (quadpill) containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or to control therapy of a single identical-appearing pill containing irbesartan 150 mg. In both arms, step-up therapy of open-label amlodipine 5 mg will be provided if blood pressure is >140/90 at 6 weeks. The primary outcome is the difference between groups in the change from baseline in mean unattended automated office systolic blood pressure at 12-week follow-up. The primary outcome and some secondary outcomes will be assessed at 12 weeks; there is an optional 12-month extension phase to assess longer-term efficacy and tolerability. Our secondary aims are to assess if this approach is safe, has fewer adverse effects, and has better tolerability compared to standard care control. QUARTET will therefore provide evidence for the effectiveness and safety of a new paradigm in the management of high blood pressure.

Low-Dose Combination Therapy for Initial Treatment of Hypertension.

PURPOSE OF REVIEW: To summarise the advances that have been made from 2017 in dual, triple, and quadruple low-dose combination therapy for treating high blood pressure. RECENT FINDINGS: Many people require multiple blood pressure lowering medicines to achieve target blood pressures, and initiating treatment with combination blood pressure lowering therapy is being increasingly investigated and recommended. Low-dose combinations of blood pressure lowering provide more effective blood pressure lowering, with fewer adverse events. Recent advances include listing of four dual combinations on the WHO Essential Medicines List, completion of a triple half-dose combination trial, and a pilot of quadruple quarter-dose combination, and recent cardiovascular polypill trials have included two blood pressure lowering medicines at low dose. These trials all demonstrated improvements in achieving blood pressure targets with low-dose combination therapy. Low-dose combination therapy is a promising option for initial treatment of hypertension that appears to be safe and effective. Larger trials of triple and quadruple low-dose combination therapy in multiple locations are underway and should provide stronger evidence of efficacy as well as information on the side effect profile.

Regression to the mean in home blood pressure: Analyses of the BP GUIDE study.

The aim of our study was to estimate the size of regression to the mean with home blood pressure (BP) monitoring and compare with that for office BP. Office and home BP measures were obtained from the BP GUIDE (value of central Blood Pressure for GUIDing managEment for hypertension) study, in which 286 patients had BP measured every 3 months for 12 months. Patients were categorized by 10 mm Hg strata of baseline BP, and regression to the mean measures was calculated for home and office BP. High baseline home BP readings tended to be lower on long-term follow-up, and low baseline readings tended to be higher. For example, patients in the group with mean baseline home systolic BP ≥ 150 mm Hg had a mean baseline systolic BP of 156 mm Hg, which fell to 143 mm Hg at 12 months; and patients in the group with mean baseline home systolic BP < 120 mm Hg had a mean baseline systolic BP of 113 mm Hg which rose to 120 mm Hg at 12 months. Similar patterns were seen in intervention and control groups, and for diastolic BP. The regression dilution ratio for home systolic BP and diastolic BP was 0.52 and 0.64, respectively, compared to 0.40 and 0.55 for office systolic BP and diastolic BP, respectively. Home BP is subject to regression to the mean to a similar degree as office BP. These findings have implications for the diagnosis and management of hypertension using home BP.

QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with coronary heart disease (QUEL): protocol for a 24-month cluster randomised controlled trial in primary care.

BACKGROUND: Cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, is the leading cause of death and disability globally. A large proportion of mortality occurs in people with prior CHD and effective and scalable strategies are needed to prevent associated deaths and hospitalisations. The aim of this study is to determine if a practice-level collaborative quality improvement program, focused on patients with CHD, reduces the rate of unplanned CVD hospitalisations and major adverse cardiovascular events, and increases the proportion of patients achieving risk factor targets at 24 months. METHODS: Cluster randomised controlled trial (cRCT) to evaluate the effectiveness of a primary care quality improvement program in 50 primary care practices (n~ 10,000 patients) with 24-month follow-up. Eligible practices will be randomised (1:1) to participate in either the intervention (collaborative quality improvement program) or control (standard care) regimens. Outcomes will be assessed based on randomised allocation, according to intention-to-treat. The primary outcome is the proportion of patients with unplanned CVD hospitalisations at 2 years. Secondary outcomes are proportion of patients with major adverse cardiovascular events, proportion of patients who received prescriptions for guideline-recommended medicines, proportion of patients achieving national risk factor targets and proportion with a chronic disease management plan or review. Differences in the proportion of patients who are hospitalised (as well as binary secondary outcomes) will be analysed using log-binomial regression or robust Poisson regression, if necessary. DISCUSSION: Despite extensive research with surrogate outcomes, to the authors' knowledge, this is the first randomised controlled trial to evaluate the effectiveness of a data-driven collaborative quality improvement intervention on hospitalisations, CVD events and cardiovascular risk amongst patients with CHD in the primary care setting. The use of data linkage for collection of outcomes will enable evaluation of this potentially efficient strategy for improving management of risk and outcomes for people with heart disease. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134 (dated 20th December 2019).

Does splitting a tablet obtain the accurate dose?: A systematic review protocol.

BACKGROUND: Physical manipulation of the manufactured dose form is a common practice, with almost a quarter of all drugs administered in primary care having their dose altered. Splitting a tablet can be advantageous as it facilitates swallowing, allows for dose flexibility and provides cost reductions. However, there are concerns these physical changes can lead to inaccurate portions resulting in significant variations from the prescribed dose. Thus, the review described in this protocol aims to summarise the literature assessing the effect of tablet splitting on dose accuracy. METHODS: Relevant studies will be identified through electronic searches in databases including EMBASE, MEDLINE, CINAHL, and the Cochrane Library, from the beginning of databases until January 2020. Studies investigating any drug, where the tablet was split, will be potentially eligible. Two reviewers will independently screen studies and extract data using standardised forms. Data extracted will include general study information, characteristics of the study, intervention characteristics and outcomes. Primary outcome is to assess dose accuracy of a split tablet measured by drug content or weight variability. Assessment of risk of bias will be dependent upon study design. If deemed feasible, meta-analysis will be performed. RESULTS: The study described within this protocol will provide a synthesis of current evidence assessing the effect of tablet splitting on dose accuracy. CONCLUSION: The conclusion of our study will provide evidence to judge whether splitting a tablet results in an accurate half dose. ETHICS AND DISSEMINATION: Ethics approval was not required for this study. The results of the systematic review described will be published in a peer-reviewed journal. REGISTRATION DETAILS: PROSPERO CRD42018106252.

Efficacy and safety of triple versus dual combination blood pressure-lowering drug therapy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Most patients with hypertension need at least two drugs to achieve goal blood pressure. This systematic review assessed efficacy and safety of triple versus dual combination therapy for the management of hypertension. METHODS: Publication databases, clinical trial registries and regulatory agency websites were searched until April 2018 for double-blind randomized controlled trials (RCTs) comparing triple with dual therapy of BP-lowering drugs, for at least 3 weeks, among patients with hypertension. Meta-analyses for efficacy and safety outcomes were performed using random-effects model. Regimen efficacy was predicted using the Therapeutic Intensity Score (TIS) and the Law et al. method (which predict dose doubling increases efficacy by 100% and around 20%, respectively), and compared with observed efficacy. RESULTS: Fourteen RCTs (11 457 participants) were included. Overall, triple compared with dual therapy reduced BP by 5.4/3.2 mmHg (P < 0.001), and improved BP control by 58 versus 45% [relative risk (RR) 1.33 (95% CI 1.25-1.41)], whereas incidence of withdrawals because of adverse events were 3.3 versus 3.4% [RR 1.24 (95% CI 1.00-1.54), P = 0.05]. Law et al.'s method was superior to TIS in predicting differences in efficacy between triple and dual therapies. For patients uncontrolled on submaximal dose dual therapy, adding a third drug achieved on average approximately four times more BP reduction than doubling the dose of dual therapy component drugs (6.0/3.6 versus 1.5/0.8 mmHg, respectively). CONCLUSION: Addition of a third drug is likely to be more efficacious without increasing adverse events, compared with increasing dose of existing dual therapy. Early use of triple therapy can significantly improve hypertension control.

Regression to the mean of repeated ambulatory blood pressure monitoring in five studies.

AIMS: To estimate the size of regression to the mean with ambulatory blood pressure (ABP) measurement. METHODS: Participants from five studies who had repeated blood pressure (BP) measurements using office and ambulatory devices were included. Regression to the mean was calculated following participants being grouped by baseline BP categories. Regression dilution ratio was calculated for groups defined by each baseline BP variable. RESULTS: High baseline ABP readings were substantially lower on long-term follow-up, and low baseline readings tended to be higher. Regression to the mean was observed for all ABP parameters; for systolic and diastolic measures; and for intervention and control groups. For example, among those with baseline 24-h SBP of at least 150 mmHg, mean baseline and follow-up BP was 156 and 141 mmHg, respectively; whereas those with baseline 24-h SBP of less than 120 mmHg, mean baseline and follow-up BP was 113 and 119 mmHg, respectively. Regression to the mean was the greatest for night-time ABP. Regression dilution ratios calculated from control groups were 0.52, 0.53, 0.38 and 0.60 for 24-h, daytime, night-time and office SBP, respectively. Similar results were seen for diastolic measures. CONCLUSION: ABP is subject to considerable regression to the mean, which has implications for diagnosis and practise; for example, after initiating treatment for hypertension some of the fall in ABP will be because of regression to the mean. Furthermore, associations of ABP with cardiovascular disease will be substantially underestimated if analyses are not adjusted for regression to the mean, especially for night-time ABP. Replication studies are needed to confirm these findings.

Use of cardiovascular prevention treatments after acute coronary syndrome in China and associated factors.

BACKGROUND: Prevention of repeat cardiovascular events is an important means of addressing the increasing burden of coronary heart disease in China, however there is minimal information about the use of cardiovascular prevention treatment following acute coronary syndrome (ACS) in China. METHODS: We analysed data from baseline and 6, 12, 18, and 24-month follow-up surveys of 15,140 consecutive ACS patients recruited in 70 hospitals from 17 provinces of China. We describe the use of indicated cardiovascular prevention medicines, risk factor control, change over time and factors associated with continued prevention. RESULTS: 12,094 patients had follow-up data up to 12months. At discharge, 86.1% were on a combination of antiplatelet, statin and blood pressure (BP) lowering drugs. Use of this combination fell to 68.0% at 12months and 59.7% in patients followed to 24months. Patients admitted to tertiary hospitals were more likely to be on the combination compared to secondary hospitals (at discharge 90.1% vs. 79.5%, p<0.0001; at 12months 71% vs. 64%, p<0.001 respectively). At 12months 25.2% achieved control in ≥four of five guideline levels of risk factors and this was similar by hospital level. Prescription of BP-lowering drugs and statins at discharge was the strongest predictor of use at 12months follow-up. Lower income was associated with less use of both. CONCLUSIONS: Use of cardiovascular prevention treatment declines steadily over time following an ACS. The largest proportional decline is in the first six months. Ensuring patients are discharged on these therapies and addressing barriers for low-income earners may help address this gap.