Process evaluation of a data-driven quality improvement program within a cluster randomised controlled trial to improve coronary heart disease management in Australian primary care.

BACKGROUND: This study evaluates primary care practices' engagement with various features of a quality improvement (QI) intervention for patients with coronary heart disease (CHD) in four Australian states. METHODS: Twenty-seven practices participated in the QI intervention from November 2019 -November 2020. A combination of surveys, semi-structured interviews and other materials within the QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease (QUEL) study were used in the process evaluation. Data were summarised using descriptive statistical and thematic analyses for 26 practices. RESULTS: Sixty-four practice team members and Primary Health Networks staff provided feedback, and nine of the 63 participants participated in the interviews. Seventy-eight percent (40/54) were either general practitioners or practice managers. Although 69% of the practices self-reported improvement in their management of heart disease, engagement with the intervention varied. Forty-two percent (11/26) of the practices attended five or more learning workshops, 69% (18/26) used Plan-Do-Study-Act cycles, and the median (Interquartile intervals) visits per practice to the online SharePoint site were 170 (146-252) visits. Qualitative data identified learning workshops and monthly feedback reports as the key features of the intervention. CONCLUSION: Practice engagement in a multi-featured data-driven QI intervention was common, with learning workshops and monthly feedback reports identified as the most useful features. A better understanding of these features will help influence future implementation of similar interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134.

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.

Ambulatory blood pressure after 12 weeks of quadruple combination of quarter doses of blood pressure medication vs. standard medication.

BACKGROUND: A combination of four ultra-low-dose blood pressure (BP) medications lowered office BP more effectively than initial monotherapy in the QUARTET trial. The effects on average ambulatory BP changes at 12 weeks have not yet been reported in detail. METHODS: Adults with hypertension who were untreated or on monotherapy were eligible for participation. Overall, 591 participants were randomized to either the quadpill (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or monotherapy control (irbesartan 150 mg). The difference in 24-h, daytime, and night-time systolic and diastolic ambulatory BP at 12 weeks along further metrics were predefined secondary outcomes. RESULTS: Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At 12 weeks, mean 24-h ambulatory SBP and DBP were 7.7 [95% confidence interval (95% CI) 9.6-5.8] and 5.3 (95% CI: 6.5-4.1) mmHg lower in the quadpill vs. monotherapy group ( P  < 0.001 for both). Similar reductions in the quadpill group were observed for daytime (8.1/5.7 mmHg lower) and night-time (6.3/4.0 mmHg lower) BP at 12 weeks (all P  < 0.001) compared to monotherapy. The rate of BP control (24-h average BP < 130/80 mmHg) at 12 weeks was higher in the quadpill group (77 vs. 50%; P  < 0.001). The reduction in BP load was also more pronounced with the quadpill. CONCLUSION: A quadruple quarter-dose combination compared with monotherapy resulted in greater ambulatory BP lowering across the entire 24-h period with higher ambulatory BP control rates and reduced BP variability at 12 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy.

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.

The effect of blood pressure lowering medications on the prevention of episodic migraine: A systematic review and meta-analysis.

BACKGROUND: Currently, only a few specific blood pressure-lowering medications are recommended for migraine prevention. Whether benefits extend to other classes or drugs is uncertain. METHODS: Embase, MEDLINE, and the Cochrane Central Registry of Controlled Trials were searched for randomized control trials on the effect of blood pressure-lowering medications compared with placebo in participants with episodic migraine. Data were collected on four outcomes - monthly headache or migraine days, and monthly headache or migraine attacks, with a standardised mean difference calculated for overall. Random effect meta-analysis was performed. RESULTS: In total, 50 trials (70% of which were crossover) were included, comprising 60 comparisons. Overall mean age was 39 years, and 79% were female. Monthly headache days were fewer in all classes compared to placebo, and this was statistically significant for all but one class: alpha-blockers -0.7 (95% CI: -1.2, -0.1), angiotensin-converting enzyme inhibitors -1.3 (95% CI: -2.9, 0.2), angiotensin II receptor blockers -0.9 (-1.6, -0.1), beta-blocker -0.4 (-0.8, -0.0) and calcium channel blockers -1.8 (-3.4, -0.2). Standardised mean difference was significantly reduced for all drug classes and was separately significant for numerous specific drugs: clonidine, candesartan, atenolol, bisoprolol, metoprolol, propranolol, timolol, nicardipine and verapamil. CONCLUSION: Among people with episodic migraine, a broader number of blood pressure-lowering medication classes and drugs reduce headache frequency than those currently included in treatment guidelines.Trial Registration: The study was registered at PROSPERO (CRD42017079176).

Efficacy and Safety of Low-Dose Triple and Quadruple Combination Pills vs Monotherapy, Usual Care, or Placebo for the Initial Management of Hypertension: A Systematic Review and Meta-analysis.

Importance: Low-dose combination (LDC) antihypertensives consisting of 3 or 4 blood pressure (BP)-lowering drugs have emerged as a potentially important therapy for the initial management of hypertension. Objective: To assess the efficacy and safety of LDC therapies for the management of hypertension. Data Sources: PubMed and Medline were searched from date of inception until September 2022. Study Selection: Randomized clinical trials comparing LDC consisting of 3 or 4 BP-lowering drugs compared to either monotherapy, usual care, or placebo. Data Extraction and Synthesis: Data were extracted by 2 independent authors and synthesized using both random and fixed-effects models using risk ratios (RR) for binary outcomes and mean differences for continuous outcomes. Main Outcomes and Measures: The primary outcome was mean reduction in systolic BP (SBP) between LDC and monotherapy, usual care, or placebo. Other outcomes of interest included the proportion of patients achieving BP less than 140/90 mm Hg, rates of adverse effects, and treatment withdrawal. Results: Seven trials with a total of 1918 patients (mean [mean range] age, 59 [50-70] years; 739 [38%] female) were included. Four trials involved triple-component LDC and 3 involved quadruple-component LDC. At 4 to 12 weeks follow-up, LDC was associated with a greater mean reduction in SBP than initial monotherapy or usual care (mean reduction, 7.4 mm Hg; 95% CI, 4.3-10.5) and placebo (mean reduction, 18.0 mm Hg; 95% CI, 15.1-20.8). LDC was associated with a higher proportion of participants achieving BP less than 140/90 mm Hg at 4 to 12 weeks compared to both monotherapy or usual care (66% vs 46%; RR, 1.40; 95% CI, 1.27-1.52) and placebo (54% vs 18%; RR, 3.03; 95% CI, 1.93-4.77). There was no significant heterogeneity between trials enrolling patients with and without baseline BP-lowering therapy. Results from 2 trials indicated LDC remained superior to monotherapy or usual care at 6 to 12 months. LDC was associated with more dizziness (14% vs 11%; RR 1.28, 95% CI 1.00-1.63) but no other adverse effects nor treatment withdrawal. Conclusions and Relevance: The findings in the study showed that LDCs with 3 or 4 antihypertensives were an effective and well-tolerated BP-lowering treatment option for the initial or early management of hypertension.

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.

Impact of various night-time period definitions on nocturnal ambulatory blood pressure.

BACKGROUND: Several definitions of night-time BP exist for the calculation of nocturnal blood pressure (BP) based on 24-h BP measurements. How much these methods differ regarding the resulting nocturnal blood pressure values, under which circumstances these differences become clinically meaningful, and under which circumstances diary-adjusted measurements should be used preferentially remains uncertain. METHODS: Data of 512 24-h BP recordings were analysed regarding differences in nocturnal BP based on three alternative definitions of night-time: 2300-0700 h, 0100-0500 h, and diary-adjusted measures. RESULTS: Mean systolic nocturnal BP between 2300-0700 h was 2.5 mmHg higher than between 0100 and 0500 h and 1.6 mmHg higher than diary adjusted estimates. Up to 38.3% of individuals showed BP differences of more than 5 mmHg when comparing temporal definitions of night-time, resulting in significant proportions of individuals being re-classified as hypertensive. When diary-derived sleeping patterns differed by less than 2 h from the 2300 to 0700 h fixed time definition, mean BP discrepancies remained below 3 mmHg. Absolute time discrepancies between diary and 2300-0700 h fixed time definition of 2-4, 4-8 or at least 8 h led to SBP/DBP differences of 4.1/3.1, 6.8/6.1, and 14.5/9.1mmHg, respectively. CONCLUSION: Average differences of nocturnal BP between varying definitions in study/cohort data are small and would be of limited relevance in many settings. However, substantial differences can be observed in individual cases, which may affect clinical decision-making in specific patients. In patients whose sleeping patterns differs by more than 2 h from defined fixed night-times, diaries should be used for adjustment.

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.

Community Group-Based Models of Medication Delivery: Applicability to Cardiovascular Diseases.

The rising global burden of chronic non-communicable diseases (NCDs) has put a strain on healthcare systems globally, especially in low- and middle-income countries, which have seen disproportionate mortality rates due to non-communicable diseases. These deaths are in part due to challenges with medication adherence, which are compounded by lack of access to medication and weak community support systems. This paper aims to propose a potential solution using models of service delivery in HIV/AIDS, given the many similarities between NCD and HIV/AIDS. Models that have been particularly effective in HIV/AIDS are the community-based peer-support medication delivery groups: medication adherence clubs and community antiretroviral therapy (ART) groups. The positive outcomes from these models, including improved medication adherence and patient satisfaction, provide evidence for their potential success when applied to non-communicable diseases, particularly hypertension and cardiovascular disease.

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.

Systematic reviews of antihypertensive drugs: A review of publication trends, characteristics, and quality.

This review presents publication trends, characteristics, and quality of systematic reviews (SRs) of randomized controlled trials (RCTs) of antihypertensive drugs (AHTDs). Between 1985 and 2017, 1,173 SRs were published, and in the last 20 years, 10, 35, and 116 were published in the year 1996, 2006, and 2016, respectively. Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers were the most common class of drugs studied. Fourteen percent of the SRs were prospectively registered/published protocol. Three-fourth of the SRs did not report a full search strategy, and 45% did not report a PRISMA or similar diagram. Of the 34 SRs published in the five high impact factor journals in the last 10 years, 15%, 21%, and 65% have unclear, low, and high risk of bias, respectively. There has been a steady increase in the publication of SRs of RCTs of AHTDs. However, adherence to standard methods of conduct and reporting continues to be low.