The cost-effectiveness of coronary calcium score-guided statin therapy initiation for Australians with family histories of premature coronary artery disease.

OBJECTIVES: To compare the cost-effectiveness of coronary artery calcium (CAC) score-guided statin therapy criteria and American College of Cardiology/American Heart Association (ACC/AHA) guidelines (10-year pooled cohort equation [PCE] risk ≥ 7.5%) with selection according to Australian guidelines (5-year absolute cardiovascular disease risk [ACVDR] ≥ 10%), for people with family histories of premature coronary artery disease. STUDY DESIGN, SETTING: Markov microsimulation state transition model based on data from the Coronary Artery calcium score: Use to Guide management of Hereditary Coronary Artery Disease (CAUGHT-CAD) trial and transition probabilities derived from published statin prescribing and adherence outcomes and clinical data. PARTICIPANTS: 1083 people with family histories of premature coronary artery disease but no symptomatic cardiovascular disease. MAIN OUTCOME MEASURES: Relative cost-effectiveness over fifteen years, from the perspective of the Australian health care system, compared with usual care (Australian guidelines), assessed as incremental cost-effectiveness ratios (ICERs), with a notional willingness-to-pay threshold of $50 000 per quality-adjusted life-year (QALY) gained. RESULTS: Applying the Australian guidelines, 77 people were eligible for statin therapy (7.1%); with ACVDR 5-year risk ≥ 2% and CAC score > 0, 496 people (46%); with ACVDR 5-year risk ≥ 2% and CAC score ≥ 100, 155 people (14%); and with the ACC/AHA guidelines, 256 people (24%). The ICERs for CAC-guided selection were $33 108 (CAC ≥ 100) and $53 028 per QALY gained (CAC > 0); the ACC/AHA guidelines approach (ICER, $909 241 per QALY gained) was not cost-effective. CAC score-guided selection (CAC ≥ 100) was cost-effective for people with 5-year ACVDR of at least 5%. CONCLUSION: Expanding the number of people at low to intermediate CVD risk eligible for statin therapy should selectively target people with subclinical atherosclerosis identified by CAC screening. This approach can be more cost-effective than simply lowering treatment eligibility thresholds.

Cost-effectiveness of dapagliflozin in chronic heart failure: an analysis from the Australian healthcare perspective.

AIM: To assess the cost-effectiveness of dapagliflozin in addition to standard care versus standard care alone in patients with chronic heart failure and reduced ejection fraction. METHODS: A Markov model was constructed based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial to assess the clinical outcomes and costs of 1000 hypothetical subjects with established heart failure and reduced ejection fraction. The model consisted of three health states: 'alive and event-free', 'alive after non-fatal hospitalisation for heart failure' and 'dead'. Costs and utilities were estimated from published sources. The main outcome was the incremental cost-effectiveness ratio per quality-adjusted life-year gained. An Australian public healthcare perspective was employed. All outcomes and costs were discounted at a rate of 5% annually. RESULTS: Over a lifetime horizon, the addition of dapagliflozin to standard care in patients with heart failure and reduced ejection fraction prevented 88 acute heart failure hospitalisations (including readmissions) and yielded an additional 416 years of life and 288 quality-adjusted life-years (discounted) at an additional cost of A$3,692,440 (discounted). This equated to an incremental cost-effectiveness ratio of A$12,482 per quality-adjusted life-year gained, well below the Australian willingness-to-pay threshold of A$50,000 per quality-adjusted life-year gained. Subanalyses in subjects with and without diabetes resulted in similar incremental cost-effectiveness ratios of A$13,234 and A$12,386 per quality-adjusted life-year gained, respectively. CONCLUSION: Dapagliflozin is likely to be cost-effective when used as an adjunct therapy to standard care compared with standard care alone for the treatment of chronic heart failure and reduced ejection fraction.

Cost-Effectiveness of Coronary Artery Calcium Scoring in People With a Family History of Coronary Disease.

OBJECTIVES: To assess the cost effectiveness of coronary artery calcium (CAC) compared with traditional risk factor-based prediction alone in those with an family history of premature coronary artery disease (FHCAD). BACKGROUND: The use of CAC scoring to guide primary prevention statin therapy in those with a FHCAD is inconsistently recommended in guidelines, and usually not reimbursed by insurance. METHODS: A microsimulation model was constructed in TreeAge Healthcare Pro using data from 1,083 participants in the CAUGHT-CAD (Coronary Artery Calcium Score: Use to Guide Management of HerediTary Coronary Artery Disease) trial. Outcomes assessed were quality-adjusted life years (QALYs): cost-effectiveness was assessed over a 15-year time horizon from the perspective of the US health care sector using real-world statin prescribing, accounting for the effect of knowledge of subclinical disease on adherence to guideline-directed therapies. Costs were assessed in 2020 USD, with discounting undertaken at 3%. RESULTS: Statins were indicated in 45% of the cohort using the CAC strategy and 27% using American College of Cardiology/American Heart Association (2019) treatment strategies. Compared with applying a statin treatment threshold of 7.5%, the CAC strategy was more costly ($145) and more effective (0.0097 QALY) with an incremental cost-effective ratio (ICER) of $15,014/QALY. CAC ICER was driven by CAC acquisition and statin prescription cost and improved with certain patient subgroups: male, age >60 years, and 10-year risk pooled cohort equation risk ≥7.5%. CAC scanning of low-risk patients (10-year risk <5%) or those 40 to 50 years of age was not cost-effective. CONCLUSIONS: Systematic CAC screening and treatment of those with FHCAD and subclinical disease was more cost-effective than management using statin treatment thresholds, in the US health care system.

Coronary artery calcium scoring in cardiovascular risk assessment of people with family histories of early onset coronary artery disease.

OBJECTIVES: To assess the predictive value of the Australian absolute cardiovascular disease risk (ACVDR) calculator and other assessment tools for identifying Australians with family histories of early onset coronary artery disease (CAD) who have coronary artery calcification. DESIGN, SETTING, PARTICIPANTS: People without known CAD were recruited at seven Australian hospitals, October 2016 - January 2019. Participants were aged 40-70 years, had a family history of early onset CAD, and a 5-year ACVDR of 2-15%. MAIN OUTCOME MEASURES: CT coronary artery calcium score greater than zero (any coronary calcification) or greater than 100 (calcification warranting lipid therapy). RESULTS: 1059 participants were recruited; 477 (45%) had non-zero coronary artery calcium scores (median 5-year ACVDR, 4.8% [IQR, 2.9-7.6%]; median coronary artery calcium score, 41.7 [IQR, 8-124]); 582 (55%) did not (median 5-year ACVDR, 3.2% [IQR, 2.0-4.6%]). Of 151 participants with calcium scores of 100 or more, 116 (77%) were deemed to be at low cardiovascular risk by Australian guidelines, while 14 of 75 participants at intermediate risk (19%) had zero calcium scores. The sensitivity of the ACVDR calculator for identifying people with non-zero calcium scores (area under receiver operator curve [AUC], 0.674) was lower than that of the pooled cohort equation (AUC, 0.711; P < 0.001). ACVDR (10-year)- and Multi-Ethnic Study of Atherosclerosis (MESA)-predicted risk categories concurred for 511 participants (48%); classifications were concordant for 925 participants (87%) when the ACVDR was supplemented by calcium scores. CONCLUSIONS: Coronary artery calcium scoring should be considered as part of the heart health check for patients at intermediate ACVDR risk and with family histories of early onset CAD. Alternative risk calculators may better select such patients for further diagnostic testing and primary prevention therapy. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN 12614001294640; 11 December 2014 (prospective).

Hypertension prevalence in patients attending tertiary pain management services, a registry-based Australian cohort study.

Persistent pain and hypertension often co-occur, and share several biological and lifestyle risk factors. The present study aimed to provide insight into the prevalence of, and factors associated with, hypertension in the largest cohort of patients seeking treatment in 43 tertiary pain clinics in Australia. Adults aged > = 18 years registered to the electronic Persistent Pain Outcomes Collaboration registry between 2013 and 2018 were included if they had persistent non-cancer pain (N = 43,789). Risk Ratios (RRs) compared prevalence of self-reported hypertension with the general and primary care Australian populations, and logistic regression examined factors associated with hypertension. One in four (23.9%) patients had hypertension, which was higher than the Australian adult population (2014-15: RR = 5.86, 95%CI: 5.66, 6.06; 2017-18: RR = 9.40, 95%CI: 9.01, 9.80), and in primary care patients (2011-13: RR = 1.17, 95%CI: 1.15, 1.20). Adjusting for covariates, patients with higher odds of hypertension were older, lived in regions with higher socioeconomic disadvantage, had higher levels of BMI, were born outside the Oceania/Australasia region, and had comorbid arthritis, diabetes, or severe-extremely severe anxiety symptoms. Female patients and those with depression symptoms had lower adjusted odds. Unadjusted analyses showed an association between widespread pain, pain duration, pain severity and interference, and lower pain self-efficacy with hypertension; however, only pain severity remained significant in adjusted analyses. Hypertension was more prevalent in people with persistent pain than in the general community, was associated with more severe pain, and commonly co-occurred with pain-related impairments. Routine hypertension screening and treatment targeting shared mechanisms of hypertension and pain may improve treatment outcomes in the pain clinic setting.

Association Between Statin Use and Depressive Symptoms in a Large Community-Dwelling Older Population Living in Australia and the USA: A Cross-Sectional Study.

BACKGROUND: Statin use has been frequently associated with depressive symptoms in an older population. However, the nature of this association is uncertain in the literature. In this study, we aimed to investigate the association of statin intake and the prevalence of depressive symptoms in healthy community-dwelling older adults living in Australia and the USA. METHODS: We analysed baseline data from 19,114 participants, over 70 years of age (over 65 years of age, if from an ethnic minority). The association of self-reported statin use and prevalence of depressive symptoms, as measured by a validated depression scale [Center for Epidemiological Studies Depression Scale (CES-D 10)], was determined using logistic regression models. Multivariable logistic models were implemented to account for important demographics and other lifestyle and socioeconomic factors, such as sex, age, living status, education and smoking history. RESULTS: A total of 5987 individuals were statin users. Of those, 633 (10.6%) had depressive symptoms (CES-D 10 cut-off ≥ 8), compared with 1246 (9.5%) of the non-statin users. In the unadjusted model, statin use was associated with an increase in prevalence of depressive symptoms (odds ratio 1.13, confidence interval 1.02-1.25, p = 0.02). However, after adjusting for important demographic and socioeconomic factors, the use of statins was not significantly associated with depressive symptoms (odds ratio 1.09, confidence interval 0.98-1.20, p = 0.11). In secondary analyses, only simvastatin was marginally associated with an increased prevalence of depressive symptoms. Statins were associated with a decreased prevalence of depressive symptoms in individuals with severe obesity (body mass index > 35 kg/m2) and an increased prevalence in participants between 75 and 84 years of age. CONCLUSION: This study in a large community-dwelling older population did not show any association of statins with late-life depressive symptoms, after accounting for important socioeconomic and demographic factors. Confounding by indication is an important issue to be addressed in future pharmacoepidemiologic studies of statins.

The cost-effectiveness of canakinumab for secondary prevention of cardiovascular disease: The Australian healthcare perspective.

BACKGROUND: Canakinumab is a fully human monoclonal antibody targeting interleukin-1ß. It is currently indicated for use in those with rheumatologic disorders due to its anti-inflammatory properties, and was recently shown to be beneficial for the secondary prevention of cardiovascular disease (CVD). However, the cost-effectiveness of canakinumab used to treat CVD is unknown. METHODS: A Markov state transition model was developed and populated with a hypothetical sample of 1000 individuals profiled on the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS); with a history of myocardial infarction (MI) and blood concentrations of high-sensitivity C-reactive protein (hsCRP) of >2 mg/L. With each annual cycle, individuals could have a recurrent non-fatal CVD event (MI or stroke), or die from a CVD event or die from other causes based on data from CANTOS. Individuals continued to cycle through the model for 20 years or until death. Cost and utility data was applied. Outcomes were discounted (5% annually). RESULTS: Over a 20-year time horizon, canakinumab is predicted to prevent 40 recurrent cardiovascular events and save 287 (discounted) years of life and 239 (discounted) quality-adjusted life years (QALYs) in 1000 individuals. At an annual cost of AUD36,049 (USD25,590, GBP19,662) per person, canakinumab would not be considered cost-effective within the Australian healthcare system, with an incremental cost-effectiveness ratio (ICER) of AUD1,221,170 per QALY gained. CONCLUSIONS: Canakinumab is an attractive treatment option to reduce recurrent CVD among patients with high hsCRP. It would be considered cost-effective in this treatment setting within the perspective of the Australian public healthcare system if its annual costs do not exceed AUD1500 (USD1065, GBP818) per person.

Cost-effectiveness of low-dose rivaroxaban and aspirin versus aspirin alone in people with peripheral or carotid artery disease: An Australian healthcare perspective.

AIMS: Peripheral artery disease affects 1.2% of the population globally and is associated with an increased risk of atherothrombotic cardiovascular events, major adverse limb events and mortality. The Cardiovascular Outcomes for People Using Anti-coagulation Strategies (COMPASS) trial demonstrated positive results of rivaroxaban plus aspirin therapy compared to aspirin therapy alone in those with peripheral artery disease or carotid artery disease. We sought to estimate the cost-effectiveness from the Australian healthcare system perspective. METHODS AND RESULTS: A Markov model was developed to simulate the experiences of a hypothetical population of 1000 individuals with peripheral artery disease or carotid artery disease, profiled on the COMPASS trial, treated with rivaroxaban plus aspirin therapy versus aspirin therapy alone. With each annual cycle, individuals were at risk of having non-fatal cardiovascular disease events, major adverse limb events, or dying. Individuals were also at risk of non-fatal major bleeding. The model had a lifetime time horizon. Costs and utilities were sourced from the literature and discounted at 5.0% annually. Rivaroxaban plus aspirin therapy prevented 143 non-fatal cardiovascular disease events, 118 major adverse limb events and 10 deaths compared to aspirin therapy alone. Conversely, 156 additional major non-fatal bleeds were accrued. With an additional 256 quality-adjusted life years gained, at an additional cost of AUD$6,858,103, the incremental cost-effectiveness ratio was AUD$26,769 (discounted) per quality-adjusted life year gained, which is below Australia's arbitrary willingness to pay threshold of AUD$50,000. CONCLUSION: In those with peripheral artery disease or carotid artery disease, rivaroxaban plus aspirin therapy is effective and cost-effective in the prevention of recurrent cardiovascular disease compared to aspirin therapy alone.

Cost-effectiveness of rivaroxaban and aspirin compared to aspirin alone in patients with stable cardiovascular disease: An Australian perspective.

OBJECTIVE: In light of the Cardiovascular Outcomes for People using Anticoagulation Strategies (COMPASS) trial, our objective was to assess the cost-effectiveness, from the Australian healthcare perspective, of rivaroxaban in combination with aspirin versus aspirin alone for the prevention of recurrent cardiovascular disease among patients with stable atherosclerotic vascular disease. METHODS: A Markov model was developed using input data from the COMPASS trial to predict the clinical course and costs of patients over a 20-year time-horizon. The model comprised of three health states: 'Alive without recurrent CVD', 'Alive after recurrent CVD' and 'Dead'. Costs were from the Australian public healthcare system perspective, and estimated from published sources, as were utility data. The costs of rivaroxaban were based on current acquisition prices on the Australian Pharmaceutical Benefits Schedule (PBS) and assumed as AUD$3.09/day. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per quality adjusted life year (QALY) gained, and cost per year of life saved (YoLS). Costs and benefits were discounted by 5.0% per year. RESULTS: Compared to aspirin alone, rivaroxaban plus aspirin was estimated to cost an additional AUD$12,156 (discounted) per person, but lead to 0.516 YoLS (discounted) and 0.386 QALYs gained (discounted), over 20 years. These equated to ICERs of AUD$23,560/YoLS and AUD$31,436/QALY gained. We have assumed a threshold of AUD$50,000/QALY gained to signify cost-effectiveness. CONCLUSION: Compared to aspirin, rivaroxaban in combination with aspirin is likely to be cost-effective in preventing recurrent cardiovascular events in patients with stable atherosclerotic vascular disease.

The cost-effectiveness of PCSK9 inhibitors - The Australian healthcare perspective.

BACKGROUND: For patients in whom statins are not tolerated or effective as monotherapy, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a new class of lipid lowering therapies that may reduce low-density lipoprotein cholesterol (LDL-C) levels by up to 50% and lower cardiovascular events. While an important treatment option, the cost-effectiveness of PCSK9i in Australia remains unknown. This study aimed to determine the cost-effectiveness of PCSK9i compared to placebo in the prevention of atherosclerotic cardiovascular disease (CVD). METHODS AND RESULTS: A Markov cohort state-transition model was developed in Microsoft Excel. A hypothetical sample of 1000 individuals based on subjects in the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial populated the model. With each five-year cycle, model subjects could have non-fatal CVD events (myocardial infarction and/or stroke), or die from CVD or other causes. Follow-up was simulated for 25 years. CVD risk reduction, cost and utility data were gathered from published sources. At current acquisition prices (AU$8174 per person per year), the incremental cost effectiveness ratio (ICER) was AU$308,558 per quality-adjusted life year (QALY) saved. Acquisition prices would need to be reduced to approximately AU$1500 per person per annum for PCSK9i to reach the arbitrary cost-effectiveness threshold of AU$50,000 per QALY saved. CONCLUSION(S): PCSK9i are an effective alternative for those with existing CVD or at high risk of CVD in whom statin therapy alone is ineffective, but are not cost-effective to the Australian healthcare system based on current prices.

Rationale and design of a trial to personalize risk assessment in familial coronary artery disease.

BACKGROUND: The lifetime risk of coronary artery disease (CAD) is doubled in people with a family history of premature disease, yet this risk is not captured in most 5- or 10-year risk assessment algorithms. Coronary artery calcium scoring (CCS) is a marker of subclinical CAD risk, which has been shown in observational studies to provide prognostic information that is incremental to clinical assessment; is relatively inexpensive; and is performed with a small radiation dose. However, the use of CCS in guiding prevention is not strongly supported by guidelines. Showing definitive evidence of the efficacy and cost-effectiveness of CCS is therefore of importance. STUDY DESIGN: The proposed randomized controlled trial of the use of CCS will be targeted to 40- to 70-year-old first-degree relatives of patients with CAD onset <60 years old or second-degree relatives of patients with onset <50 years old. Control patients will undergo standard risk scoring and be blinded to CCS results. In the intervention group, primary prevention in patients undergoing CCS will be informed by this score. At 3 years, effectiveness will be assessed on change in plaque volume at computed tomography coronary angiography, the extent of which has been strongly linked to outcome. SUMMARY: The CAUGHT-CAD trial will provide evidence to inform the guidelines regarding the place of CCS in decision making regarding primary prevention of patients with a family history of premature disease.

Mind the Gap: Mismatches Between Clinicians and Patients in Heart Failure Medication Management.

PURPOSE: Previous studies on the 'treatment gap' in patients with heart failure (HF) have focused either on prescribing or patients' adherence to prescribed treatment. This study sought to determine whether or not recent initiatives to close the gap have also minimised any mismatches between physicians' expectation of their patients' medications, medications in the patients' possession and their actual medication use. METHODS: A cross-sectional observational survey was conducted from December 2015 to June 2016 in The Alfred Hospital HF clinic in Melbourne, Australia. Patients were invited to participate if they had chronic HF (NYHA class II to IV), were aged ≥ 60 years, had no history of HF related hospitalisation within the past 6 months and were prescribed at least two HF medications. RESULTS: Of 123 eligible patients, 102 were recruited into the study. Beta-blockers, mineralocorticoid receptor antagonists, loop diuretics and statins were associated with the highest rates of mismatches of drugs and doses, ranging from 10 to 17%. Discrepancy of total daily doses was the most common type of mismatch. Overall, only 23.5% of the patients were taking the right drugs at the right doses as expected by their cardiologists/HF specialists. CONCLUSIONS: Despite improved prescribers' adherence to guideline-directed medical therapy, there remain considerable mismatches between prescribers' expectation of patients' HF medications, medications in patients' possession and their actual medication use. Initiatives to improve this situation are urgently needed.

Adherence and Persistence Among Statin Users Aged 65 Years and Over: A Systematic Review and Meta-analysis.

Background: Older people (aged ≥ 65 years) have distinctive challenges with medication adherence. However, adherence and persistence patterns among older statin users have not been comprehensively reviewed. Methods: As part of a broader systematic review, we searched Medline, Embase, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects, CENTRAL, and the National Health Service Economic Evaluation Database through December 2016 for English articles reporting adherence and/or persistence among older statin users. Data were analyzed via descriptive methods and meta-analysis using random-effect modeling. Results: Data from more than 3 million older statin users in 82 studies conducted in over 40 countries were analyzed. At 1-year follow-up, 59.7% (primary prevention 47.9%; secondary prevention 62.3%) of users were adherent (medication possession ratio [MPR] or proportion of days covered [PDC] ≥ 80%). For both primary and secondary prevention subjects, 1-year adherence was worse among individuals aged more than 75 years than those aged 65-75 years. At 3 and ≥10 years, 55.3% and 28.4% of users were adherent, respectively. The proportion of users persistent at 1-year was 76.7% (primary prevention 76.0%; secondary prevention 82.6%). Additionally, 68.1% and 61.2% of users were persistent at 2 and 4 years, respectively. Among new statin users, 48.2% were nonadherent and 23.9% discontinued within the first year. The proportion of statin users who were adherent based on self-report was 85.5%. Conclusions: There is poor short and long term adherence and persistence among older statin users. Strategies to improve adherence and reduce discontinuation are needed if the intended cardiovascular benefits of statin treatment are to be realized.

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.

Patterns and Predictors of Adherence to Statin Therapy Among Older Patients: Protocol for a Systematic Review.

BACKGROUND: The benefits of statin therapy are significantly compromised by noncompliance. Although elderly patients may have particular challenges with medication adherence and persistence, previous reviews on statin adherence have not focused on this population. Additionally, comparisons of adherence and persistence specific to statin indication (primary or secondary prevention) have not been thoroughly explored. OBJECTIVE: We aim to assess the extent of, and factors associated with, adherence and persistence to statin therapy among older populations (aged ≥65 years). METHODS: A systematic review will be undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Searches will be performed using multiple electronic databases (Ovid MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and the National Health Service Economic Evaluation Database) to identify relevant randomized trials and observational studies that evaluated statin adherence and/or persistence as an outcome. Eligible studies will include those involving community-living or outpatient elderly individuals. The methodological quality of randomized controlled trials (RCTs) will be assessed via the Joanna Briggs Institute's critical appraisal checklist for RCTs, and the quality assessment of observational studies will be undertaken using a set of questions formulated with resort to the National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. When possible, meta-analyses will be conducted using random-effect modeling and generic inverse variance analyses for adjusted-effect estimates. Heterogeneity across studies will be quantified using the I2 statistic. The presence of publication bias will be assessed using funnel plots and Egger's regression tests. A leave-one-out sensitivity analysis will also be conducted to assess the impact of individual study results on pooled estimates. To explore possible sources of heterogeneity across studies, subgroup analyses will be performed based on covariates such as study design, statin indication, country of study, and length of patient follow-up. RESULTS: The electronic database searches were completed in December 2016. Retrieved articles are currently being screened and the entire study is expected to be completed by June 2017. CONCLUSIONS: This systematic review will provide further understanding of the patterns of, and barriers to, statin adherence and persistence among older patients. The findings will inform clinical practice and the design of appropriate interventions. TRIAL REGISTRATION: PROSPERO CRD42016053191.

Development of an Australian cardiovascular disease mortality risk score using multiple imputation and recalibration from national statistics.

OBJECTIVE: To develop and recalibrate an Australian 5-year cardiovascular disease (CVD) mortality risk score to produce contemporary predictions of risk. METHODS: Data were pooled from six Australian cohort studies (n = 54,829), with baseline data collected between 1989 and 2003. Participants included were aged 40-74 years and free of CVD at baseline. Variables were harmonised across studies and missing data were imputed using multiple imputation. Cox proportional hazards models were used to estimate the risk of CVD mortality associated with factors mutually independently predictive (p < 0.05) and a 5-year risk prediction algorithm was constructed. This algorithm was recalibrated to reflect contemporary national levels of CVD mortality and risk factors using national statistics. RESULTS: Over a mean 16.6 years follow-up, 1375 participants in the six studies died from CVD. The prediction model included age, sex, smoking, diabetes, systolic blood pressure, total and high-density lipoprotein cholesterol (HDLC), a social deprivation score, estimated glomerular filtration rate and its square and interactions of sex with diabetes, HDLC and deprivation score, and of age with systolic blood pressure and smoking. This model discriminated well when applied to a Scottish study population (c-statistic (95% confidence interval): 0.751 (0.709, 0.793)). Recalibration generally increased estimated risks, but well below those predicted by the European SCORE models. CONCLUSIONS: The resulting risk score, which includes markers of both chronic kidney disease and socioeconomic deprivation, is the first CVD mortality risk prediction tool for Australia to be derived using Australian data. The primary model, and the method of recalibration, is applicable elsewhere.

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.

Semiparametric methods for multistate survival models in randomised trials.

Transform methods have proved effective for networks describing a progression of events. In semi-Markov networks, we calculated the transform of time to a terminating event from corresponding transforms of intermediate steps. Saddlepoint inversion then provided survival and hazard functions, which integrated, and fully utilised, the network data. However, the presence of censored data introduces significant difficulties for these methods. Many participants in controlled trials commonly remain event-free at study completion, a consequence of the limited period of follow-up specified in the trial design. Transforms are not estimable using nonparametric methods in states with survival truncated by end-of-study censoring. We propose the use of parametric models specifying residual survival to next event. As a simple approach to extrapolation with competing alternative states, we imposed a proportional incidence (constant relative hazard) assumption beyond the range of study data. No proportional hazards assumptions are necessary for inferences concerning time to endpoint; indeed, estimation of survival and hazard functions can proceed in a single study arm. We demonstrate feasibility and efficiency of transform inversion in a large randomised controlled trial of cholesterol-lowering therapy, the Long-Term Intervention with Pravastatin in Ischaemic Disease study. Transform inversion integrates information available in components of multistate models: estimates of transition probabilities and empirical survival distributions. As a by-product, it provides some ability to forecast survival and hazard functions forward, beyond the time horizon of available follow-up. Functionals of survival and hazard functions provide inference, which proves sharper than that of log-rank and related methods for survival comparisons ignoring intermediate events.

Access to cardiac rehabilitation does not equate to attendance.

BACKGROUND/AIMS: Timely access to appropriate cardiac care is critical for optimizing positive outcomes after a cardiac event. Attendance at cardiac rehabilitation (CR) remains less than optimal (10%-30%). Our aim was to derive an objective, comparable, geographic measure reflecting access to cardiac services after a cardiac event in Australia. METHODS: An expert panel defined a single patient care pathway and a hierarchy of the minimum health services for CR and secondary prevention. Using geographic information systems a numeric/alpha index was modelled to describe access before and after a cardiac event. The aftercare phase was modelled into five alphabetical categories: from category A (access to medical service, pharmacy, CR, pathology within 1 h) to category E (no services available within 1 h). RESULTS: Approximately 96% or 19 million people lived within 1 h of the four basic services to support CR and secondary prevention, including 96% of older Australians and 75% of the indigenous population. Conversely, 14% (64,000) indigenous people resided in population locations that had poor access to health services that support CR after a cardiac event. CONCLUSION: Results demonstrated that the majority of Australians had excellent 'geographic' access to services to support CR and secondary prevention. Therefore, it appears that it is not the distance to services that affects attendance. Our 'geographic' lens has identified that more research on socioeconomic, sociological or psychological aspects to attendance is needed.

Assessment of cardiovascular disease risk in South asian populations.

Although South Asian populations have high cardiovascular disease (CVD) burden in the world, their patterns of individual CVD risk factors have not been fully studied. None of the available algorithms/scores to assess CVD risk have originated from these populations. To explore the relevance of CVD risk scores for these populations, literature search and qualitative synthesis of available evidence were performed. South Asians usually have higher levels of both "classical" and nontraditional CVD risk factors and experience these at a younger age. There are marked variations in risk profiles between South Asian populations. More than 100 risk algorithms are currently available, with varying risk factors. However, no available algorithm has included all important risk factors that underlie CVD in these populations. The future challenge is either to appropriately calibrate current risk algorithms or ideally to develop new risk algorithms that include variables that provide an accurate estimate of CVD risk.