Switching, Persistence and Adherence to Statin Therapy: a Retrospective Cohort Study Using the Australian National Pharmacy Data.

BACKGROUND: Statins are widely prescribed for the primary and secondary prevention of cardiovascular disease (CVD), but their effectiveness is dependent on the level of adherence and persistence. OBJECTIVES: This study aimed to explore the patterns of switching, adherence and persistence among the Australian general population with newly dispensed statins. METHODS: A retrospective cohort study was conducted using a random sample of data from the Australian national prescription claims data. Switching, adherence to and persistence with statins were assessed for people starting statins from 1 January 2015 to 31 December 2019. Switching was defined as either switching to another intensity of statin, to another statin or to a non-statin agent. Non-persistence to treatment was defined as discontinuation (i.e. ≥90 days with no statin) of coverage. Adherence was measured using proportion of days covered (PDC), and patients with PDC < 0.80 were considered non-adherent. Cox proportional hazard models were used to compare discontinuation, switching and reinitiation between different statins. RESULTS: A cohort of 141,062 people dispensed statins and followed over a median duration of 2.5 years were included. Of the cohort, 29.3% switched statin intensity, 28.4% switched statin type, 3.7% switched to ezetimibe and in 2.7%, ezetimibe was added as combination therapy during the study period. Overall, 58.8% discontinued statins based on the 90-day gap criteria, of whom 55.2% restarted. The proportion of people non-adherent was 24.0% at 6 months to 49.0% at 5 years. People on low and moderate intensity statins were more likely to discontinue compared to those on high-intensity statins (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.31), (HR 1.28, 95%CI 1.14-1.42), respectively. Compared to maintaining same statin type and intensity, switching statins, which includes up-titration (HR 0.77, 95%CI 0.70 to 0.86) was associated with less likelihood of discontinuation after reinitiation. CONCLUSIONS: Long-term persistence and adherence to statins remains generally poor among Australians, which limits the effectiveness of these medicines and the consequent health impact they may provide for individuals (and by extension, the population impact when poor persistence and adherence is considered in the statin-taking population). Switching between statins is prevalent in one third of statin users, although any clinical benefit of the observed switching trend is unknown. This, combined with the high volume of statin prescriptions, highlights the need for better strategies to address poor persistence and adherence.

The influence of aortic stiffness on carotid stiffness: computational simulations using a human aorta carotid model.

Increased aortic and carotid stiffness are independent predictors of adverse cardiovascular events. Arterial stiffness is not uniform across the arterial tree and its accurate assessment is challenging. The complex interactions and influence of aortic stiffness on carotid stiffness have not been investigated. The aim of this study was to evaluate the effect of aortic stiffness on carotid stiffness under physiological pressure conditions. A realistic patient-specific geometry was used based on magnetic resonance images obtained from the OsiriX library. The luminal aortic-carotid model was reconstructed from magnetic resonance images using 3D Slicer. A series of aortic stiffness simulations were performed at different regional aortic areas (levels). By applying variable Young's modulus to the aortic wall under two pulse pressure conditions, one could examine the deformation, compliance and von Mises stress between the aorta and carotid arteries. An increase of Young's modulus in an aortic area resulted in a notable difference in the mechanical properties of the aortic tree. Regional deformation, compliance and von Mises stress changes across the aorta and carotid arteries were noted with an increase of the aortic Young's modulus. Our results indicate that increased carotid stiffness may be associated with increased aortic stiffness. Large-scale clinical validation is warranted to examine the influence of aortic stiffness on carotid stiffness.

Comparison of Parameters for Assessment of Carotid Stiffness and Their Association with Carotid Atherosclerosis in Rural Australian Adults: A Pilot Study.

Carotid stiffness has been associated with the development and progression of carotid artery disease and is an independent factor for stroke and dementia. There has also been a lack of comparison of different ultrasound-derived carotid stiffness parameters and their association with carotid atherosclerosis. This pilot study aimed to investigate the associations between carotid stiffness parameters (derived via ultrasound echo tracking) and the presence of carotid plaques in Australian rural adults. In cross-sectional analyses, we assessed forty-six subjects (68 ± 9 years; mean ± SD) who underwent carotid ultrasound examinations. Carotid stiffness was assessed by a noninvasive echo-tracking method, measuring and comparing multiple carotid stiffness parameters, including stroke change in diameter (ΔD), stroke change in lumen area (ΔA), ß- stiffness index, pulse wave velocity beta (PWV-ß), compliance coefficient (CC), distensibility coefficient (DC), Young's elastic modulus (YEM), Peterson elastic modulus (Ep), and strain. Carotid atherosclerosis was assessed bilaterally by the presence of plaques in the common and internal carotid arteries, while carotid stiffness was assessed at the right common carotid artery. ß-stiffness index, PWV-ß, and Ep were significantly higher (p = 0.006, p = 0.004, p = 0.02, respectively), whilst ΔD, CC, DC, and strain were lower among subjects with carotid plaques (p = 0.036, p = 0.032, p = 0.01, p = 0.02, respectively) comparing to subjects without carotid plaques. YEM and ΔA did not significantly differ among the groups. Carotid plaques were associated with age, history of stroke, coronary artery disease, and previous coronary interventions. These results suggest that unilateral carotid stiffness is associated with the presence of carotid plaques.

Future burden of cardiovascular disease in Australia: impact on health and economic outcomes between 2020 and 2029.

AIMS: To estimate the health and economic burden of new and established cardiovascular disease from 2020 to 2029 in Australia. METHODS AND RESULTS: A two-stage multistate dynamic model was developed to predict the burden of the incident and prevalent cardiovascular disease, for Australians 40-90 years old from 2020 to 2029. The model captured morbidity, mortality, years of life lived, quality-adjusted life years, healthcare costs, and productivity losses. Cardiovascular risk for the primary prevention population was derived using Australian demographic data and the Pooled Cohort Equation. Risk for the secondary prevention population was derived from the REACH registry. Input data for costs and utilities were extracted from published sources. All outcomes were annually discounted by 5%. A number of sensitivity analyses were undertaken to test the robustness of the study. Between 2020 and 2029, the model estimates 377 754 fatal and 991 375 non-fatal cardiovascular events. By 2029, 1 061 756 Australians will have prevalent cardiovascular disease (CVD). The population accrued 8 815 271 [95% uncertainty interval (UI) 8 805 083-8 841 432] years of life lived with CVD and 5 876 975 (5 551 484-6 226 045) QALYs. The total healthcare costs of CVD were projected to exceed Australian dollars (AUD) 61.89 (61.79-88.66) billion, and productivity losses will account for AUD 78.75 (49.40-295.25) billion, driving the total cost to surpass AUD 140.65 (123.13-370.23) billion. CONCLUSION: Cardiovascular disease in Australia has substantial impacts in terms of morbidity, mortality, and lost revenue to the healthcare system and the society. Our modelling provides important information for decision making in relation to the future burden of cardiovascular disease.

Attainment of low-density lipoprotein cholesterol goals in statin treated patients: Real-world evidence from Australia.

Little is known about the attainment of low-density lipoprotein cholesterol (LDL-C) targets in patients treated with statins in Australian primary healthcare setting that are at increased risk of cardiovascular disease. A retrospective cohort study was conducted using data from electronic medical records of patients treated by general practitioners across Australia. LDL-C target attainment was defined as LDL-C levels ≤ 2 mmol/L for all risk groups, in line with Australian guidelines. Multivariable logistic regression was used to identify the factors associated with LDL-C target attainment. Overall, 61,407 patients were included in the analysis. The mean age was 65 years (± standard deviation [SD] 12.1); 52.0% were males.. Overall, the median LDL-C level was 2.3 mmol/L (IQR = 1.8 - 2.8) and 36.0% of the study population met therapeutic targets. Increased likelihood to achieve LDL-C targets was observed in patients diagnosed with type 2 diabetes (OR 2.07, 95% CI 1.92 - 2.24), stroke (OR = 1.58, 95% CI 1.39 - 1.79, P < 0.001) or chronic heart disease (OR = 1.67, 95% CI 1.55 - 1.81, P < 0.001). Patients diagnosed with dyslipidemia (OR = 0.59, 95% CI 0.55 - 0.64, P < 0.001), hypertension (OR = 0.91, 95% CI 0.83 - 1.00, P < 0.05) and current smokers (OR = 0.71, 95% CI 0.71 - 1.00, P < 0.05), were less likely to attain LDL-C targets, regardless of the type, intensity and length of use of the prescribed statin. Longer duration and higher intensity statin were associated with more patients achieving targeted LDL-C goal, however nearly two thirds of Australians still failed to achieve targeted outcome even after 24 months of statin therapy.

Attainment of low-density lipoprotein cholesterol goals in patients treated with combination therapy: A retrospective cohort study in primary care.

BACKGROUND: The attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in real-world settings among patients receiving combination lipid-lowering therapy (LLT, statins plus non-statins) is not well characterised. OBJECTIVE: To evaluate LDL-C levels and LDL-C goal attainment in patients treated with combination LLT in real-world primary care settings. METHODS: A retrospective cohort study of patients treated with combination LLT. Data were drawn from general practitioner electronic medical records across Australia from 2013 to 2019. The on-treatment goal for LDL-C was < 2 mmol/L (77 mg/dL), as per Australian guidelines. RESULTS: The cohort analysed included 9,173 individuals treated with combination LLT. The mean age was 65.8 years (standard deviation [SD] 11.5), 60.1% were males, and 56.7% had at least one cardiovascular risk factor. The median on-treatment LDL-C was 2.1 mmol/L (IQR 1.6-2.8), and overall 45.4% of the cohort met LDL-C goals, with individuals on fixed-dose combination of statins plus ezetimibe having the highest rates of achievement (49.8%). In multivariable logistic regression analyses, factors associated with LDL-C goal achievement were male sex (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.3-1.6, p < 0.001), aged >80 years (OR 4.2, 95% CI 1.5 - 6.6, p = 0.006), and a history of T2DM (OR 1.7; 95% CI 1.5-1.9, p < 0.001) or coronary heart disease (OR 1.4, 95% CI 1.2 - 1.6, p < 0.001). CONCLUSIONS: More than half of Australians on combination LLT did not achieve LDL-C goals. Urgent measures are needed to address this gap in clinical practice to minimise negative health outcomes.

Trends in the Utilization of Lipid-Lowering Medications in Australia: An Analysis of National Pharmacy Claims Data.

Lipid-lowering medications comprise standard of care in the prevention of cardiovascular disease. This study examined the trends in the utilization of statin and non-statin medications in the Australian general population between 2013 and 2019. Pharmacoepidemiological analyses were performed using pharmacy dispensing data from Australian Pharmaceutical Benefits Scheme. One-year prevalence and incidence of statin and non-statin prescribing patterns were reported, and relative variations in prescribing examined via Poisson regression modelling. The one-year prevalence of statins' prescriptions decreased between 2013-2019 by 5.5% (from 25.0%-19.5%). Females were less likely than males to be prescribed statins (rate ratio [RR]=0.90, 95% confidence interval [CI] 0.89-0.91). The one-year prevalence of ezetimibe alone, and in combination with statins, increased consistently from 2013-2019 from 1.5%-3.6% (P<0.01) and 0.1%-1.1% (P<0.01), respectively. The prevalence was higher among those aged 61-80 years (RR=1.20, 95%CI 1.10-1.21) and those aged older than 80 years (RR=1.34, 95%CI 1.22-1.47), when compared to people aged <60 years. The incidence of ezetimibe prescriptions was highest in people aged 61-80 years (RR=1.36, 95%CI 1.31-1.41) compared to those aged <60 years. The one-year prevalence of proprotein convertase subtilisin/kexin type 9 inhibitor prescriptions was highest among those aged 46-60 years (RR=1.24, 95%CI 0.97-4.97) compared to people aged <46 and >60 years. Females were less likely than males to be prescribed a proprotein convertase subtilisin/kexin type 9 inhibitor (RR=0.87, 95%CI 0.75-0.98). Statins remain the most prevalent lipid-lowering medication prescribed in Australia. The prescribing of non-statin medications remains low, but is increasing.

Carotid Ultrasound Screening Programs in Rural Communities: A Systematic Review.

Carotid atherosclerosis assessments inform about stroke and cardiovascular risk. It is known that stroke and cardiovascular disease (CVD) prevalence is higher in rural communities than in urban communities. We aimed to conduct a systematic review of rural carotid ultrasound screening programs to define carotid atherosclerosis using traditional and emerging imaging biomarkers, prevalence, and risk factors. We searched Ovid/MEDLINE, Ovid/EMBASE, SCOPUS and CINAHL from inception to 3 April 2020 for rural population studies that utilized carotid ultrasound screening for adults ≥40 years of age and free of known cerebrovascular disease. Studies were included if participants received a bilateral ultrasound scanning of the carotid arteries and reported at least one marker of carotid atherosclerosis pathology. A random effect meta-analyses calculated the estimated prevalence of carotid plaque. In total, 22/3461 articles that met all of the inclusion criteria were included. Studies reported increased intima media thickness (IMT), carotid plaque presence and carotid artery stenosis. There were no studies reporting on novel imaging markers, such as carotid stiffness, carotid plaque morphology or neovascularization. The overall random effect pooled prevalence of carotid plaque was 34.1% (95% CI, 33.6-35.0); the prevalence of increased IMT was 11.2-41.5%, and the prevalence of carotid artery stenosis was 0.4-16.0%. There is an absence of data necessary to understand the carotid atherosclerosis prevalence across global rural populations. Represented studies have focused on East Asian countries where a high burden of rural carotid artery disease has been reported. There is no rural evidence to guide the use of novel ultrasound carotid biomarkers such as stiffness or neovascularization.