The Pathophysiology, Prognosis and Treatment of Hypertension in Females from Pregnancy to Post-menopause: A Review.

PURPOSE OF REVIEW: We summarise the physiological changes and risk factors for hypertension in females, potential sex-specific management approaches, and long-term prognosis. KEY FINDINGS: Pregnancy and menopause are two key phases of the life cycle where females undergo significant biological and physical changes, making them more prone to developing hypertension. Gestational hypertension occurs from changes in maternal cardiac output, kidney function, metabolism, or placental vasculature, with one in ten experiencing pregnancy complications such as intrauterine growth restriction and delivery complications such as premature birth. Post-menopausal hypertension occurs as the protective effects of oestrogen are reduced and the sympathetic nervous system becomes over-activated with ageing. Increasing evidence suggests that post-menopausal females with high blood pressure (BP) experience greater risk of cardiovascular events at lower BP thresholds, and greater vulnerability to treatment-related adverse effects. Hypertension is a key risk factor for cardiovascular disease in females. Current BP treatment guidelines and recommendations are similar for both sexes, without addressing sex-specific factors. Future investigations into ideal diagnostic thresholds, BP control targets and treatment regimens in females are needed.

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.

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.

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).

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.

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.

Gender Difference in Secondary Prevention of Cardiovascular Disease and Outcomes Following the Survival of Acute Coronary Syndrome.

BACKGROUND: Previous studies have shown that women with acute coronary syndrome (ACS) are less likely to receive in-hospital care such as revascularisation procedures and secondary prevention medications. Therefore, the aim was to determine if the rate of secondary preventive care and outcomes also differ by sex in patients with ACS at 6 and 12 months after discharge. METHODS: Of ACS patients recruited from 43 hospitals between 2009 to 2018, 9,283 were discharged alive and followed up at 6 months as part of the Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events (CONCORDANCE) registry. Multivariable logistic regression models within the framework of generalised estimating equations were used to compare the rate of medication use, smoking, cardiac rehabilitation participation, major adverse cardiovascular event (MACE: myocardial infarction, heart failure or stroke) and all-cause death at 6 and 12 months after discharge between female and male patients. RESULTS: Of 9,283 ACS patients, 2,676 (29%) were women. At 6-month post discharge, women were more likely to have comorbidities than men. After adjusting for clinical characteristics, women had lower odds of attending cardiac rehabilitation than men (OR [95% CI]: 0.87 [0.78, 0.98]) and no sex difference in the odds of using ≥75% of the indicated medications or smoking. Women had higher odds of having a MACE compared to men (1.35 [1.03, 1.77]) but there was no difference for all-cause death between women and men. Moreover, at 12 months after discharge, women were less likely to be on ≥75% of the indicated medications (0.84 [0.75, 0.95]) but no difference was found in the odds of smoking, MACE and all-cause death. CONCLUSION: Our findings from a large contemporary Australian registry dataset suggest that women attend cardiac rehabilitation programs less often and are more likely to have a MACE at 6 months of surviving ACS. At 12 months post discharge, women were less likely to use the indicated secondary prevention medications. Development of effective secondary prevention methods tailored to women are needed.

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.

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.

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).

Exposure to body diversity images as a buffer against the thin-ideal: An experimental study.

There has recently been a call for the use of more diverse images by the media to promote body satisfaction. This experimental study evaluated the impact of body diversity images and whether these could act as a buffer against thin-ideal norms. Female participants (n = 106, aged 16-30 years) completed measures of body compassion, body and face satisfaction before and after random allocation to images reflecting one of three interventions: control, body diversity and thin-ideal. Attitudes towards thin-ideal images were also assessed. The results showed significant differences between groups for overall body compassion, the body compassion subtype of body kindness, body satisfaction and face satisfaction with those viewing the body diversity images reporting higher scores after exposure compared to the other two groups. Those in the body diversity group also displayed more negative attitudes towards thin-ideal images compared to controls. No between groups differences were found for body compassion subtypes relating to common humanity, motivated action and body criticism or positive attitudes to the thin-ideal images. In sum, exposure to body diversity images had a positive impact on body kindness and overall body compassion and body satisfaction providing experimental support for the use of diversity images as a buffer against thin-deals.

Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review.

BACKGROUND: Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. METHODS: We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill-a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis. FINDINGS: Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14-23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen. INTERPRETATION: The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability. FUNDING: National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.

Missing Voices: Profile, Extent, and 12-Month Outcomes of Nonfatal Traumatic Brain Injury in Aboriginal and Non-Aboriginal Adults in Western Australia Using Linked Administrative Records.

OBJECTIVE: To investigate differences in the profile and outcomes between Aboriginal and non-Aboriginal Western Australians (WAs) hospitalized with traumatic brain injury (TBI). SETTING: WA hospitals. PARTICIPANTS: TBI cases aged 15 to 79 years surviving their first admission during 2002-2011. DESIGN: Patients identified from diagnostic codes and followed up for 12 months or more using WA-wide person-based linked hospital and mortality data. MAIN MEASURES: Demographic profile, 5-year comorbidity history, injury mechanism, injury severity, 12-month readmission, and mortality risks. Determinants of 12-month readmission. RESULTS: Of 16 601 TBI survivors, 14% were Aboriginal. Aboriginal patients were more likely to be female, live remotely, and have comorbidities. The mechanism of injury was an assault in 57% of Aboriginal patients (vs 20%) and transport in 33% of non-Aboriginal patients (vs 17%), varying by remoteness. One in 10 Aboriginal TBI patients discharged themselves against medical advice. Crude 12-month readmission but not mortality risk was significantly higher in Aboriginal patients (48% vs 36%). The effect of age, sex, and injury mechanism on 12-month readmission was different for Aboriginal and non-Aboriginal patients. CONCLUSION: These findings suggest an urgent need for multisectoral primary prevention of TBI, as well as culturally secure and logistically appropriate medical and rehabilitation service delivery models to optimize outcomes.

Cardiovascular disease risk and comparison of different strategies for blood pressure management in rural India.

BACKGROUND: Non-optimal blood pressure (BP) levels are a major cause of disease burden globally. We describe current BP and treatment patterns in rural India and compare different approaches to BP lowering in this setting. METHODS: All individuals aged ≥40 years from 54 villages in a South Indian district were invited and 62,194 individuals (84%) participated in a cross-sectional study. Individual 10-year absolute cardiovascular disease (CVD) risk was estimated using WHO/ISH charts. Using known effects of treatment, proportions of events that would be averted under different paradigms of BP lowering therapy were estimated. RESULTS: After imputation of pre-treatment BP levels for participants on existing treatment, 76·9% (95% confidence interval, 75.7-78.0%), 5·3% (4.9-5.6%), and 17·8% (16.9-18.8%) of individuals had a 10-year CVD risk defined as low (< 20%), intermediate (20-29%), and high (≥30%, established CVD, or BP > 160/100 mmHg), respectively. Compared to the 19.6% (18.4-20.9%) of adults treated with current practice, a slightly higher or similar proportion would be treated using an intermediate (23·2% (22.0-24.3%)) or high (17·9% (16.9-18.8%) risk threshold for instituting BP lowering therapy and this would avert 87·2% (85.8-88.5%) and 62·7% (60.7-64.6%) more CVD events over ten years, respectively. These strategies were highly cost-effective relative to the current practice. CONCLUSION: In a rural Indian community, a substantial proportion of the population has elevated CVD risk. The more efficient and cost-effective clinical approach to BP lowering is to base treatment decisions on an estimate of an individual's short-term absolute CVD risk rather than with BP based strategy. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/2013/06/003753 , 14 June 2013.

Healthcare resource utilisation by patients with coronary heart disease receiving a lifestyle-focused text message support program: an analysis from the TEXT ME study.

The 'Tobacco, Exercise and Diet Messages' (TEXT ME) study was a 6-month, single-centre randomised clinical trial (RCT) that found a text message support program improved levels of cardiovascular risk factors in patients with coronary heart disease (CHD). The current analyses examined whether receipt of text messages influenced participants' engagement with conventional healthcare resources. The TEXT ME study database (N=710) was linked with routinely collected health department databases. Number of doctor consultations, investigations and cardiac medication prescriptions in the two study groups were compared. The most frequently accessed health service was consultations with a General Practitioner (mean 7.1, s.d. 5.4). The numbers of medical consultations, biochemical tests or cardiac-specific investigations were similar between the study groups. There was at least one prescription registered for statin, ACEI/ARBs and ß-blockers in 79, 66 and 50% of patients respectively, with similar refill rates in both the study groups. The study identified TEXT ME text messaging program did not increase use of Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) captured healthcare services. The observed benefits of TEXT ME reflect direct effects of intervention independent of conventional healthcare resource engagement.

Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis.

BACKGROUND: Recent hypertension guidelines have reversed previous recommendations for lower blood pressure targets in high-risk patients, such as those with cardiovascular disease, renal disease, or diabetes. This change represents uncertainty about whether more intensive blood pressure-lowering strategies are associated with greater reductions in risk of major cardiovascular and renal events. We aimed to assess the efficacy and safety of intensive blood pressure-lowering strategies. METHODS: For this updated systematic review and meta-analysis, we systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between Jan 1, 1950, and Nov 3, 2015. We included randomised controlled trials with at least 6 months' follow-up that randomly assigned participants to more intensive versus less intensive blood pressure-lowering treatment, with different blood pressure targets or different blood pressure changes from baseline. We did not use any age or language restrictions. We did a meta-analysis of blood pressure reductions on relative risk (RR) of major cardiovascular events (myocardial infarction, stroke, heart failure, or cardiovascular death, separately and combined), and non-vascular and all-cause mortality, end-stage kidney disease, and adverse events, as well as albuminuria and progression of retinopathy in trials done in patients with diabetes. FINDINGS: We identified 19 trials including 44,989 participants, in whom 2496 major cardiovascular events were recorded during a mean 3·8 years of follow-up (range 1·0-8·4 years). Our meta-analysis showed that after randomisation, patients in the more intensive blood pressure-lowering treatment group had mean blood pressure levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group. Intensive blood pressure-lowering treatment achieved RR reductions for major cardiovascular events (14% [95% CI 4-22]), myocardial infarction (13% [0-24]), stroke (22% [10-32]), albuminuria (10% [3-16]), and retinopathy progression (19% [0-34]). However, more intensive treatment had no clear effects on heart failure (15% [95% CI -11 to 34]), cardiovascular death (9% [-11 to 26]), total mortality (9% [-3 to 19]), or end-stage kidney disease (10% [-6 to 23]). The reduction in major cardiovascular events was consistent across patient groups, and additional blood pressure lowering had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes. Serious adverse events associated with blood pressure lowering were only reported by six trials and had an event rate of 1·2% per year in intensive blood pressure-lowering group participants, compared with 0·9% in the less intensive treatment group (RR 1·35 [95% CI 0·93-1·97]). Severe hypotension was more frequent in the more intensive treatment regimen (RR 2·68 [1·21-5·89], p=0·015), but the absolute excess was small (0·3% vs 0·1% per person-year for the duration of follow-up). INTERPRETATION: Intensive blood pressure lowering provided greater vascular protection than standard regimens. In high-risk patients, there are additional benefits from more intensive blood pressure lowering, including for those with systolic blood pressure below 140 mmHg. The net absolute benefits of intensive blood pressure lowering in high-risk individuals are large. FUNDING: National Health and Medical Research Council of Australia.

Rapid-access cardiology services: can these reduce the burden of acute chest pain on Australian and New Zealand health services?

Chest pain is common and places a significant burden on hospital resources. Many patients with undifferentiated low- to intermediate-risk chest pain are admitted to hospital. Rapid-access cardiology (RAC) services are hospital co-located, cardiologist-led outpatient clinics that provide rapid assessment and immediate management but not long-term management. This service model is described as part of chest pain management and the National Service Framework for coronary heart disease in the United Kingdom (UK). We review the evidence on the effectiveness, safety and acceptability of RAC services. Our review finds that early assessment in RAC outpatient services of patients with suspected angina, without high-risk features suspicious of an acute coronary syndrome, is safe, can reduce hospitalisations, is cost effective and has good medical practitioner and patient acceptability. However, the literature is limited in that the evaluation of this model of care has been only in the UK. It is potentially suited to other settings and needs further evaluation in other settings to assess its utility.

Utilisation of Medicare-funded schemes for people with cardiovascular disease.

The aim of this study is to investigate the utilisation of Medicare Benefit Scheme items for chronic disease in the management of cardiovascular disease (CVD) in general practice and to compare characteristics of CVD patients with and without a General Practice Management Plan (GPMP). Subgroup analysis of Treatment of Cardiovascular Risk using Electronic Decision Support (TORPEDO) baseline data was collected in a cohort comprising 6123 patients with CVD. The mean age (s.d.) was 71 (±13) years, 55% were male, 64% had a recorded diagnosis of coronary heart disease, 31% also had a diagnosis of diabetes and the mean number of general practice (GP) visits (s.d.) was 11 (±9) in 12 months. A total of 1955/6123 (32%) received a GPMP in the 12 months before data extraction; 1% received a Mental Health Plan. Factors associated with greater likelihood of receiving a GPMP were: younger age, had a diagnosis of diabetes, BMI > 30kgm-2, prescription of blood pressure-lowering therapy and more than ten general practice visits. Enhancing utilisation of existing schemes could augment systematic follow up and support of patients with CVD.