Effect of interventions to improve safety culture on healthcare workers in hospital settings: a systematic review of the international literature.

BACKGROUND: In an era of safety systems, hospital interventions to build a culture of safety deliver organisational learning methodologies for staff. Their benefits to hospital staff are unknown. We examined the literature for evidence of staff outcomes. Research questions were: (1) how is safety culture defined in studies with interventions that aim to enhance it?; (2) what effects do interventions to improve safety culture have on hospital staff?; (3) what intervention features explain these effects? and (4) what staff outcomes and experiences are identified? METHODS AND ANALYSIS: We conducted a mixed-methods systematic review of published literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was conducted in MEDLINE, EMBASE, CINAHL, Health Business Elite and Scopus. We adopted a convergent approach to synthesis and integration. Identified intervention and staff outcomes were categorised thematically and combined with available data on measures and effects. RESULTS: We identified 42 articles for inclusion. Safety culture outcomes were most prominent under the themes of leadership and teamwork. Specific benefits for staff included increased stress recognition and job satisfaction, reduced emotional exhaustion, burnout and turnover, and improvements to working conditions. Effects were documented for interventions with longer time scales, strong institutional support and comprehensive theory-informed designs situated within specific units. DISCUSSION: This review contributes to international evidence on how interventions to improve safety culture may benefit hospital staff and how they can be designed and implemented. A focus on staff outcomes includes staff perceptions and behaviours as part of a safety culture and staff experiences resulting from a safety culture. The results generated by a small number of articles varied in quality and effect, and the review focused only on hospital staff. There is merit in using the concept of safety culture as a lens to understand staff experience in a complex healthcare system.

Videos of simulated after action reviews: a training resource to support social and inclusive learning from patient safety events.

Innovation in the education and training of healthcare staff is required to support complementary approaches to learning from patient safety and everyday events in healthcare. Debriefing is a commonly used learning tool in healthcare education but not in clinical practice. Little is known about how to implement debriefing as an approach to safety learning across a health system. After action review (AAR) is a debriefing approach designed to help groups come to a shared mental model about what happened, why it happened and to identify learning and improvement. This paper describes a digital-based implementation strategy adapted to the Irish healthcare system to promote AAR uptake. The digital strategy aims to assist implementation of national level incident management policies and was collaboratively developed by the RCSI University of Medicine and Health Sciences and the National Quality and Patient Safety Directorate of the Health Service Executive. During the COVID-19 pandemic, a well-established in-person AAR training programme was disrupted and this led to the development of a series of open access videos on AAR facilitation skills (which accompany the online version of this paper). These provide: (1) an introduction to the AAR facilitation process; (2) a simulation of a facilitated formal AAR; (3) techniques for handling challenging situations that may arise in an AAR and a (4) reflection on the benefits of the AAR process. These have the potential to be used widely to support learning from patient safety and everyday events including excellent care.

'What effect do safety culture interventions have on health care workers in hospital settings?' A systematic review of the international literature.

Introduction: Interventions designed to improve safety culture in hospitals foster organisational environments that prevent patient safety events and support organisational and staff learning when events do occur. A safety culture supports the required health workforce behaviours and norms that enable safe patient care, and the well-being of patients and staff. The impact of safety culture interventions on staff perceptions of safety culture and patient outcomes has been established. To-date, however, there is no common understanding of what staff outcomes are associated with interventions to improve safety culture and what staff outcomes should be measured. Objectives: The study seeks to examine the effect of safety culture interventions on staff in hospital settings, globally. Methods and Analysis: A mixed methods systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches will be conducted using the electronic databases of MEDLINE, EMBASE, CINAHL, Health Business Elite, and Scopus. Returns will be screened in Covidence according to inclusion and exclusion criteria. The mixed-methods appraisal tool (MMAT) will be used as a quality assessment tool. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials and non-randomised studies of interventions will be employed to verify bias. Synthesis will follow the Joanna Briggs Institute methodological guidance for mixed methods reviews, which recommends a convergent approach to synthesis and integration. Discussion: This systematic review will contribute to the international evidence on how interventions to improve safety culture may support staff outcomes and how such interventions may be appropriately designed and implemented.

Effect of after action review on safety culture and second victim experience and its implementation in an Irish hospital: A mixed methods study protocol.

BACKGROUND: After Action Review is a form of facilitated team learning and review of events. The methodology originated in the United States Army and forms part of the Incident Management Framework in the Irish Health Services. After Action Review has been hypothesized to improve safety culture and the effect of patient safety events on staff (second victim experience) in health care settings. Yet little direct evidence exists to support this and its implementation has not been studied. AIM: To investigate the effect of After Action Review on safety culture and second victim experience and to examine After Action Review implementation in a hospital setting. METHODS: A mixed methods study will be conducted at an Irish hospital. To assess the effect on safety culture and second victim experience, hospital staff will complete surveys before and twelve months after the introduction of After Action Review to the hospital (Hospital Survey on Safety Culture 2.0 and Second Victim Experience and Support Tool). Approximately one in twelve staff will be trained as After Action Review Facilitators using a simulation based training programme. Six months after the After Action Review training, focus groups will be conducted with a stratified random sample of the trained facilitators. These will explore enablers and barriers to implementation using the Theoretical Domains Framework. At twelve months, information will be collected from the trained facilitators and the hospital to establish the quality and resource implications of implementing After Action Review. DISCUSSION: The results of the study will directly inform local hospital decision-making and national and international approaches to incorporating After Action Review in hospitals and other healthcare settings.

The Irish National Adverse Event Study-2 (INAES-2): longitudinal trends in adverse event rates in the Irish healthcare system.

OBJECTIVES: To quantify the prevalence and nature of adverse events in acute Irish hospitals in 2015 and to assess the impact of the National Clinical Programmes and the National Clinical Guidelines on the prevalence of adverse events by comparing these results with the previously published data from 2009. DESIGN AND METHODS: A retrospective chart review of 1605 admissions to eight Irish hospitals in 2015, using identical methods to those used in 2009. RESULTS: The percentage of admissions associated with one or more adverse events was unchanged (p=0.48) at 14% (95% CI=10.4% to 18.4%) in 2015 compared with 12.2% (95% CI=9.5% to 15.5%) in 2009. Similarly, the prevalence of preventable adverse events was unchanged (p=0.3) at 7.4% (95% CI=5.3% to 10.5%) in 2015 compared with 9.1% (95% CI=6.9% to 11.9%) in 2009. The incidence densities of preventable adverse events were 5.6 adverse events per 100 admissions (95% CI=3.4 to 8.0) in 2015 and 7.7 adverse events per 100 admissions (95% CI=5.8 to 9.6) in 2009 (p=0.23). However, the percentage of preventable adverse events due to hospital-associated infections decreased to 22.2% (95% CI=15.2% to 31.1%) in 2015 from 33.1% (95% CI=25.6% to 41.6%) in 2009 (p=0.01). CONCLUSION: Adverse event rates remained stable between 2009 and 2015. The percentage of preventable adverse events related to hospital-associated infection decreased, which may represent a positive impact of the related national programmes and guidelines.

National and Institutional Trends in Adverse Events Over Time: A Systematic Review and Meta-analysis of Longitudinal Retrospective Patient Record Review Studies.

OBJECTIVE: This study aimed to determine if the implementation of large-scale patient safety initiatives have been successful in reducing overall and preventable adverse event rates in hospital inpatients. DESIGN: The design used in this study was systematic review and meta-analysis. DATA RESOURCES: We followed our published protocol (PROSPERO [CRD42019140058]) and searched the following databases: PubMed, CINAHL, PsycINFO, Cochrane Library, and Embase from inception to February 2020. The reference lists of eligible studies were also searched. ELIGIBILITY: All longitudinal retrospective record review studies that examined adverse event rates before and after the introduction of patient safety initiatives in hospital inpatients were included. DATA EXTRACTION: Data extraction, quality, and risk of bias assessment were carried out by 2 independent reviewers. Information on study design, setting, demographics, interventions, and safety outcome measures was extracted. RESULTS: A total of 3894 articles were screened, and 7 articles met the eligibility criteria for our systematic review with 5 of these providing sufficient information for inclusion in the meta-analysis. The degree of heterogeneity was high among studies. The meta-analysis demonstrated a minimal risk reduction in overall adverse event rates of 0.017 (95% confidence interval, 0.002-0.032) when the lower-quality studies were excluded, with one adverse event being prevented for every 59 hospital admissions. CONCLUSIONS: These findings are significant when the large numbers of admissions to a hospital every year are considered. Given the low numbers of large-scale implementation studies, there is a need for more research on the effectiveness of patient safety initiatives to further assess the impact of such initiatives on adverse events.

Reaching cardiovascular prevention guideline targets with a polypill-based approach: a meta-analysis of randomised clinical trials.

OBJECTIVE: The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. METHODS: We conducted an individual participant data meta-analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. RESULTS: Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0-1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3.07 (95% CI 1.77 to 5.33, 35% vs 11%), respectively. CONCLUSIONS: Polypill-based therapy significantly improved the achievement of all three ESC targets for BP, LDL and antiplatelet therapy compared with usual care, particularly among those undertreated at baseline.

Healthcare expenditure on Indigenous and non-Indigenous Australians at high risk of cardiovascular disease.

BACKGROUND: In spite of bearing a heavier burden of death, disease and disability, there is mixed evidence as to whether Indigenous Australians utilise more or less healthcare services than other Australians given their elevated risk level. This study analyses the Medicare expenditure and its predictors in a cohort of Indigenous and non-Indigenous Australians at high risk of cardiovascular disease. METHODS: The healthcare expenditure of participants of the Kanyini Guidelines Adherence with the Polypill (GAP) pragmatic randomised controlled trial was modelled using linear regression methods. 535 adult (48% Indigenous) participants at high risk of cardiovascular disease (CVD) were recruited through 33 primary healthcare services (including 12 Aboriginal Medical Services) across Australia. RESULTS: There was no significant difference in the expenditure of Indigenous and non-Indigenous participants in non-remote areas following adjustment for individual characteristics. Indigenous individuals living in remote areas had lower MBS expenditure ($932 per year P < 0.001) than other individuals. MBS expenditure was found to increase with being aged over 65 years ($128, p = 0.013), being female ($472, p = 0.003), lower baseline reported quality of life ($102 per 0.1 decrement of utility p = 0.004) and a history of diabetes ($324, p = 0.001), gout ($631, p = 0.022), chronic obstructive pulmonary disease ($469, p = 0.019) and established CVD whether receiving guideline-recommended treatment prior to the trial ($452, p = 0.005) or not ($483, p = 0.04). When controlling for all other characteristics, morbidly obese patients had lower MBS expenditure than other individuals (-$887, p = 0.002). CONCLUSION: The findings suggest that for the majority of participants, once individuals are engaged with a primary care provider, factors other than whether they are Indigenous determine the level of Medicare expenditure for each person. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 126080005833347.

The impact of a point-of-care testing device on CVD risk assessment completion in New Zealand primary-care practice: A cluster randomised controlled trial and qualitative investigation.

OBJECTIVES: To assess the effect of a point of care (POC) device for testing lipids and HbA1c in addition to testing by community laboratory facilities (usual practice) on the completion of cardiovascular disease (CVD) risk assessments in general practice. METHODS: We conducted a pragmatic, cluster randomised controlled trial in 20 New Zealand general practices stratified by size and rurality and randomised to POC device plus usual practice or usual practice alone (controls). Patients aged 35-79 years were eligible if they met national guideline criteria for CVD risk assessment. Data on CVD risk assessments were aggregated using a web-based decision support programme common to each practice. Data entered into the on-line CVD risk assessment form could be saved pending blood test results. The primary outcome was the proportion of completed CVD risk assessments. Qualitative data on practice processes for CVD risk assessment and feasibility of POC testing were collected at the end of the study by interviews and questionnaire. The POC testing was supported by a comprehensive quality assurance programme. RESULTS: A CVD risk assessment entry was recorded for 7421 patients in 10 POC practices and 6217 patients in 10 control practices; 99.5% of CVD risk assessments had complete data in both groups (adjusted odds ratio 1.02 [95%CI 0.61-1.69]). There were major external influences that affected the trial: including a national performance target for CVD risk assessment and changes to CVD guidelines. All practices had invested in systems and dedicated staff time to identify and follow up patients to completion. However, the POC device was viewed by most as an additional tool rather than as an opportunity to review practice work flow and leverage the immediate test results for patient education and CVD risk management discussions. Shortly after commencement, the trial was halted due to a change in the HbA1c test assay performance. The trial restarted after the manufacturing issue was rectified but this affected the end use of the device. CONCLUSIONS: Performance incentives and external influences were more powerful modifiers of practice behaviours than the POC device in relation to CVD risk assessment completion. The promise of combining risk assessment, communication and management within one consultation was not realised. With shifts in policy focus, the utility of POC devices for patient engagement in CVD preventive care may be demonstrated if fully integrated into the clinical setting. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000607774.

The Irish National Adverse Events Study (INAES): the frequency and nature of adverse events in Irish hospitals-a retrospective record review study.

INTRODUCTION: Irish healthcare has undergone extensive change recently with spending cuts and a focus on quality initiatives; however, little is known about adverse event occurrence. OBJECTIVE: To assess the frequency and nature of adverse events in Irish hospitals. METHODS: 1574 (53% women, mean age 54 years) randomly selected adult inpatient admissions from a sample of eight hospitals, stratified by region and size, across the Republic of Ireland in 2009 were reviewed using two-stage (nurse review of patient charts, followed by physician review of triggered charts) retrospective chart review with electronic data capture. Results were weighted to reflect the sampling strategy. The impact on adverse event rate of differing application of international adverse event criteria was also examined. RESULTS: 45% of charts were triggered. The prevalence of adverse events in admissions was 12.2% (95% CI 9.5% to 15.5%), with an incidence of 10.3 events per 100 admissions (95% CI 7.5 to 13.1). Over 70% of events were considered preventable. Two-thirds were rated as having a mild-to-moderate impact on the patient, 9.9% causing permanent impairment and 6.7% contributing to death. A mean of 6.1 added bed days was attributed to events, representing an expenditure of €5550 per event. The adverse event rate varied substantially (8.6%-17.0%) when applying different published adverse event eligibility criteria. CONCLUSIONS: This first study of adverse events in Ireland reports similar rates to other countries. In a time of austerity, adverse events in adult inpatients were estimated to cost over €194 million. These results provide important baseline data on the adverse event burden and, alongside web-based chart review, provide an incentive and methodology to monitor future patient-safety initiatives.

Using run charts for cardiovascular disease risk assessments in general practice.

INTRODUCTION Run charts are quality improvement tools. AIM To investigate the feasibility and acceptability of run charts displaying weekly cardiovascular disease (CVD) risk assessments in general practice and assess their impact on CVD risk assessments. METHODS A controlled non-randomised observational study in nine practices using run charts and nine control practices. We measured the weekly proportion of eligible patients with completed CVD risk assessments for 19 weeks before and after run charts were introduced into intervention practices. A random coefficients model determined changes in CVD risk assessment rates (slope) from pre- to post- intervention by aggregating and comparing intervention and control practices' mean slopes. We interviewed staff in intervention practices about their use of run charts. RESULTS Seven intervention practices used their run chart; six consistently plotting weekly data for >12 weeks and positioning charts in a highly visible place. Staff reported that charts were easy to use, a visual reminder for ongoing team efforts, and useful for measuring progress. There were no significant differences between study groups: the mean difference in pre- to post-run chart slope in the intervention group was 0.03% more CVD risk assessments per week; for the control group the mean difference was 0.07%. The between group difference was 0.04% per week (95% CI: -0.26 to 0.35, P = 0.77). DISCUSSION Run charts are feasible in everyday general practice and support team processes. There were no differences in CVD risk assessment between the two groups, likely due to national targets driving performance at the time of the study.

Dispensing data captures individual-level use of aspirin for cardiovascular disease prevention, despite availability over-the-counter.

AIM: To assess the level of agreement in aspirin use measured by self-report and dispensing data. METHOD: We assessed preventive cardiovascular medication use (prescription-only statins and blood pressure-lowering therapy; and aspirin-also available over-the-counter) at baseline in participants in the New Zealand IMPACT trial for whom these medications were prescribed by their general practitioner. A trial nurse not involved in their ongoing health care obtained participants' self-reported aspirin use data. We obtained dispensing data from the national pharmaceutical dispensing database and assessed agreement between the two measures using kappa coefficients. RESULTS: Of the 513 trial participants, 36% were women, 50% were of Maori ethnicity, and 45% had a history of cardiovascular disease. The level of agreement between self-reported aspirin use and dispensing data was substantial (kappa 0.75, 95% CI 0.69 to 0.82). The level of agreement in aspirin use measured by these two sources of data was similar to that for statin and blood pressure-lowering therapy use, for all participants combined, for subgroups according to ethnicity (Maori and non-Maori) and history of cardiovascular disease. CONCLUSIONS: Despite its availability over-the-counter, aspirin use in patients for whom cardiovascular medications are indicated can be assessed accurately from dispensing data.

Polypill-based therapy likely to reduce ethnic inequities in use of cardiovascular preventive medications: Findings from a pragmatic randomised controlled trial.

OBJECTIVE: The purpose of this study was to investigate the consistency of the proportional effect of fixed-dose combination therapy (the 'polypill') on the use of recommended cardiovascular preventative medications among indigenous Maori and non-indigenous adults in New Zealand. METHODS: We randomised Maori and non-Maori primary care patients at high risk of cardiovascular disease (either because of a prior event or with an estimated 5-year risk of a first event of at least 15%) to a polypill (containing aspirin, statin and two antihypertensives) or usual care for a minimum of 12 months. All patients had indications for all polypill components according to their general practitioner, and all medications (including the polypill) were prescribed by the patient's general practitioner and dispensed at community pharmacies. The main outcome for this study was the use of all recommended medications (antiplatelet, statin and two antihypertensives) at 12 months. Heterogeneity in the effect of polypill-based care compared with usual care on this outcome by ethnicity was assessed by logistic regression. RESULTS: Baseline use of recommended medications was 36% (93/257) among Maori and 51% (130/156) among non-Maori participants. Polypill-based care was associated with an increase in the use of recommended medications among Maori (relative risk [RR]: 1.87; 95% confidence interval [CI]: 1.50-2.34) and non-Maori (RR: 1.66; 95% CI: 1.37-2.00) when compared with usual care at 12 months, and there was no statistically significant heterogeneity in this outcome by ethnicity (p = 0.92). CONCLUSION: Polypill-based care is likely to reduce absolute inequities between Maori and non-Maori in the use of recommended cardiovascular preventative medications given baseline absolute differences and the consistency of the proportional effect of this intervention by ethnicity in this pragmatic trial in primary care.

Do polypills lead to neglect of lifestyle risk factors? Findings from an individual participant data meta-analysis among 3140 patients at high risk of cardiovascular disease.

AIM: The aim of this study was to investigate whether polypill-based care for the prevention of cardiovascular disease (CVD) is associated with a change in lifestyle risk factors when compared with usual care, among patients with CVD or high calculated cardiovascular risk. METHODS: We conducted an individual participant data meta-analysis of three trials including patients from Australia, England, India, Ireland, the Netherlands and New Zealand that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior CVD event or who were at high risk of their first event. Analyses investigated any differential effect on anthropometric measures and self-reported lifestyle behaviours. RESULTS: Among 3140 patients (75% male, mean age 62 years and 76% with a prior CVD event) there was no difference in lifestyle risk factors in those randomised to polypill-based care compared with usual care over a median of 15 months, either across all participants combined, or in a range of subgroups. Furthermore, narrow confidence intervals (CIs) excluded any major effect; for example differences between the groups in body mass index was -0.1 (95% CI -0.2 to 0.1) kg/m(2), in weekly duration of moderate intensity physical activity was -2 (-26 to 23) minutes and the proportion of smokers was 16% vs 17% (RR 0.98, 0.84 to 1.15) at the end of trial. DISCUSSION: This analysis allays concern that polypill-based care may lead to neglect of lifestyle risk factors, at least among high-risk patients. Maximally effective preventive approaches should address lifestyle factors alongside pharmaceutical interventions, as recommended by major international guidelines.

Effectiveness of fixed dose combination medication ('polypills') compared with usual care in patients with cardiovascular disease or at high risk: A prospective, individual patient data meta-analysis of 3140 patients in six countries.

AIMS: To conduct a prospective, individual participant data (IPD) meta-analysis of randomised controlled trials comparing a polypill-based approach with usual care in high risk individuals. METHODS AND RESULTS: Three trials comparing polypill-based care with usual care in individuals with CVD or high calculated cardiovascular risk contributed IPD. Primary outcomes were self-reported adherence to combination therapy (anti-platelet, statin and ≥ two blood pressure (BP) lowering agents), and difference in mean systolic BP (SBP) and LDL-cholesterol at 12 months. Analyses used random effects models. Among 3140 patients from Australia, England, India, Ireland, New Zealand and The Netherlands (75% male, mean age 62 years), median follow-up was 15 months. At baseline, 84%, 87% and 61% respectively were taking a statin, anti-platelet agent and at least two BP lowering agents. At 12 months, compared to usual care, participants in the polypill arm had higher adherence to combination therapy (80% vs. 50%, RR 1.58; 95% CI, 1.32 to 1.90; p < 0.001), lower SBP (-2.5 mmHg; 95% CI, -4.5 to -0.4; p = 0.02) and lower LDL-cholesterol (-0.1 mmol/L; 95% CI, -0.2 to 0.0; p = 0.04). Baseline treatment levels were a major effect modifier for adherence and SBP (p-homog < 0.0001 and 0.02 respectively) with greatest improvements seen among those under-treated at baseline. CONCLUSIONS: Polypill therapy significantly improved adherence, SBP and LDL-cholesterol in high risk patients compared with usual care, especially among those who were under-treated at baseline.

The Effect of a Cardiovascular Polypill Strategy on Pill Burden.

AIMS: Recent trials of cardiovascular polypills in high-risk populations show improvements in the use of cardiovascular preventive treatments, compared to usual care. We describe patterns of pill burden in Australian practice, define the impact of polypill therapy on pill burden, and explore how physicians add medication to polypill therapy. METHODS: The Kanyini Guidelines Adherence with the Polypill Study was an open-label trial involving 623 participants in Australia which randomized participants to a polypill strategy (containing a statin, antiplatelet agent, and two blood-pressure-lowering medications) or usual care. Participants either had established cardiovascular disease or were at high calculated risk (≥15% over 5 years). Current medications, daily pill burden, and self-reported use of combination treatment were recorded prior to randomization and at study end. Median pill burden at baseline and study end was compared in both arms. Subgroup analysis of the polypill strategy on trial primary outcomes was conducted by pill burden at baseline. RESULTS: Median total and cardiovascular pill burdens of the polypill group decreased from 7 to 5 and from 4 to 2, respectively (median change -2; IQR -3, 0), with no change in the usual care group (comparison of change; P < 0.001). No change was seen for noncardiovascular medications. Of those still using the polypill at study end, 43.8% were prescribed additional medications; 84.5% of these additional medications were blood-pressure-lowering medications. Within the polypill group, lower pill burden at baseline was associated with greater increases in the use of indicated cardiovascular preventive medications at study end compared to those with higher pill burdens. No trend was observed between the level of baseline pill burden and the effect of poylpill treatment on systolic blood pressure or total cholesterol. CONCLUSION: A cardiovascular polypill in contemporary Australian practice reduces cardiovascular and total pill burdens, despite frequent prescription of additional medications.

A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk.

BACKGROUND: Most individuals at high cardiovascular disease (CVD) risk worldwide do not receive any or optimal preventive drugs. We aimed to determine whether fixed dose combinations of generic drugs ('polypills') would promote use of such medications. METHODS: We conducted a randomized, open-label trial involving 623 participants from Australian general practices. Participants had established CVD or an estimated five-year CVD risk of ≥15%, with indications for antiplatelet, statin and ≥2 blood pressure lowering drugs ('combination treatment'). Participants randomized to the 'polypill-based strategy' received a polypill containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Participants randomized to 'usual care' continued with separate medications and doses as prescribed by their doctor. Primary outcomes were self-reported combination treatment use, systolic blood pressure and total cholesterol. RESULTS: After a median of 18 months, the polypill-based strategy was associated with greater use of combination treatment (70% vs. 47%; relative risk 1.49, (95% confidence interval (CI) 1.30 to 1.72) p < 0.0001; number needed to treat = 4.4 (3.3 to 6.6)) without differences in systolic blood pressure (-1.5 mmHg (95% CI -4.0 to 1.0) p = 0.24) or total cholesterol (0.08 mmol/l (95% CI -0.06 to 0.22) p = 0.26). At study end, 17% and 67% of participants in polypill and usual care groups, respectively, were taking atorvastatin or rosuvastatin. CONCLUSION: Provision of a polypill improved self-reported use of indicated preventive treatments. The lack of differences in blood pressure and cholesterol may reflect limited study power, although for cholesterol, improved statin use in the polypill group counter-balanced use of more potent statins with usual care.

An economic case for a cardiovascular polypill? A cost analysis of the Kanyini GAP trial.

OBJECTIVE: To measure the costs of a polypill strategy and compare them with those of usual care in people with established cardiovascular disease (CVD) or at similarly high cardiovascular risk. DESIGN: A within-trial cost analysis of polypill-based care versus usual care with separate medications, using data from the Kanyini Guidelines Adherence with the Polypill (GAP) trial and linked health service and medication administrative claims data. PARTICIPANTS: Kanyini GAP participants who consented to Australian Medicare record access. MAIN OUTCOME MEASURES: Mean health service and pharmaceutical expenditure per patient per year, estimated with generalised linear models. Costs during the trial (randomisation January 2010 - May 2012, median follow-up 19 months, maximum follow-up 36 months) were inflated to 2012 costs. RESULTS: Our analysis showed a statistically significantly lower mean pharmaceutical expenditure of $989 (95% CI, $648-$1331) per patient per year in the polypill arm compared with usual care (P < 0.001; adjusted, excluding polypill cost). No significant difference was shown in health service expenditure. CONCLUSIONS: This study provides evidence of significant cost savings to the taxpayer and Australian Government through the introduction of a CVD polypill strategy. The savings will be less now than during the trial due to subsequent reductions in the costs of usual care. Nonetheless, given the prevalence of CVD in Australia, the introduction of this polypill could increase considerably the efficiency of health care expenditure in Australia. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN126080005833347.

Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease: randomised controlled trial in primary care.

OBJECTIVE: To evaluate whether provision of fixed dose combination treatment improves adherence and risk factor control compared with usual care of patients at high risk of cardiovascular disease in primary care. DESIGN: Open label randomised control trial: IMPACT (IMProving Adherence using Combination Therapy). SETTING: 54 general practices in the Auckland and Waikato regions of New Zealand, July 2010 to August 2013. PARTICIPANTS: 513 adults (including 257 indigenous Maori) at high risk of cardiovascular disease (established cardiovascular disease or five year risk ≥ 15%) who were recommended for treatment with antiplatelet, statin, and two or more blood pressure lowering drugs. 497 (97%) completed 12 months' follow-up. INTERVENTIONS: Participants were randomised to continued usual care or to fixed dose combination treatment (with two versions available: aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg with either atenolol 50 mg or hydrochlorothiazide 12.5 mg). All drugs in both treatment arms were prescribed by their usual general practitioners and dispensed by local community pharmacists. MAIN OUTCOME MEASURES: Primary outcomes were self reported adherence to recommended drugs (antiplatelet, statin, and two or more blood pressure lowering agents) and mean change in blood pressure and low density lipoprotein cholesterol at 12 months. RESULTS: Adherence to all four recommended drugs was greater among fixed dose combination than usual care participants at 12 months (81% v 46%; relative risk 1.75, 95% confidence interval 1.52 to 2.03, P<0.001; number needed to treat 2.9, 95% confidence interval 2.3 to 3.7). Adherence for each drug type at 12 months was high in both groups but especially in the fixed dose combination group: for antiplatelet treatment it was 93% fixed dose combination v 83% usual care (P<0.001), for statin 94% v 89% (P=0.06), for combination blood pressure lowering 89% v 59% (P<0.001), and for any blood pressure lowering 96% v 91% (P=0.02). Self reported adherence was highly concordant with dispensing data (dispensing of all four recommended drugs 79% fixed dose combination v 47% usual care, relative risk 1.67, 95% confidence interval 1.44 to 1.93, P<0.001). There was no statistically significant improvement in risk factor control between the fixed dose combination and usual care groups over 12 months: the difference in systolic blood pressure was -2.2 mm Hg (-4.5 v -2.3, 95% confidence interval -5.6 to 1.2, P=0.21), in diastolic blood pressure -1.2 mm Hg (-2.1 v -0.9, -3.2 to 0.8, P=0.22) and in low density lipoprotein cholesterol -0.05 mmol/L (-0.20 v -0.15, -0.17 to 0.08, P=0.46). The number of participants with cardiovascular events or serious adverse events was similar in both treatment groups (fixed dose combination 16 v usual care 18 (P=0.73), 99 v 93 (P=0.56), respectively). Fixed dose combination treatment was discontinued in 94 participants (37%). The most commonly reported reason for discontinuation was a side effect (54/75, 72%). Overall, 89% (227/256) of fixed dose combination participants' general practitioners completed a post-trial survey, and the fixed dose combination strategy was rated as satisfactory or very satisfactory for starting treatment (206/227, 91%), blood pressure control (180/220, 82%), cholesterol control (170/218, 78%), tolerability (181/223, 81%), and prescribing according to local guidelines (185/219, 84%). When participants were asked at 12 months how easy they found taking their prescribed drugs, most responded very easy or easy (224/246, 91% fixed dose combination v 212/246, 86% usual care, P=0.09). At 12 months the change in other lipid fractions, difference in EuroQol-5D, and difference in barriers to adherence did not differ significantly between the treatment groups. CONCLUSIONS: Among this well treated primary care population, fixed dose combination treatment improved adherence to the combination of all recommended drugs but improvements in clinical risk factors were small and did not reach statistical significance. Acceptability was high for both general practitioners and patients, although the discontinuation rate was high. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12606000067572.

Prospective meta-analysis of trials comparing fixed dose combination based care with usual care in individuals at high cardiovascular risk: the SPACE Collaboration.

BACKGROUND: An international collaboration of investigators will assess the benefits and risks of fixed dose combination (FDC) based care compared with usual care in populations at high risk of cardiovascular disease (CVD). Several trials are being conducted, as the effectiveness and economic impact of a FDC-based strategy may vary substantially between countries, given the varying influence of the health-care system within which the intervention is delivered. METHODS: Individual patient data (IPD) will be provided by participating trials for combined IPD meta-analysis. RESULTS: Primary outcomes will include self-reported current use of antiplatelet, statin, and combination (≥ 2) blood pressure lowering therapies at 12 months, and change in systolic blood pressure (SBP) and LDL cholesterol from baseline to 12 months. Non-inferiority margins of 3 mm Hg for SBP and 0.3 mmol/L for LDL cholesterol have been pre-specified. Secondary outcomes will include change in cholesterol fractions, diastolic blood pressure and creatinine from baseline to 12 months, quality of life, new onset diabetes mellitus, mortality (cardiovascular, non-cardiovascular and all cause) and a composite outcome of cardiovascular events (including all coronary heart disease events, heart failure events leading to death or requiring hospital admission, cerebrovascular events and peripheral arterial events). CONCLUSION: The SPACE group of trials will assess, in a variety of healthcare settings, whether a FDC strategy for delivery of preventive medication has the potential to significantly improve prevention of cardiovascular disease in patients at high risk.