Pharmacotherapeutics in Cardiovascular Disease Research Program

Theme leader

Dr Stella Talic

Dr Talic is a clinical pharmacoepidemiologist that specialises in researching chronic disease therapeutic management using Real-World Evidence (RWE) methods.

RWE provides evidence of the utilisation and potential benefits or risks of a medical product, in this case the medicines. Common sources include electronic health records (EHRs), hospital episode data, insurance claims data, patient registry data, clinical audits, and observational cohort studies. RWE provides a more complete picture of treatment effectiveness within a real-world patient population by overcoming design limitations of clinical trials. By applying RWE to her studies, Dr Talic ensures the findings are immediately relevant and translatable.

Our current work focuses on understanding the complex relationship between cardiovascular medications and long-term clinical outcomes by studying utilisation, adherence and persistence patterns, as well as safety, and effectiveness of medications in managing CV conditions. We strive to influence health policy decisions and clinical guidelines to ultimately improve long-term cardiovascular disease management and reduce the burden of CVD.

Key projects led by our team

ACTIVE STUDIES

Pharmacoepidemiological studies on utilisation, persistence and adherence of... View

Pharmacoepidemiological studies on utilisation, persistence and adherence of cardiovascular-related medications

Chief Investigators

Dr Stella Talic

Background

Adherence with prescribed medication regimes is a major factor in attaining clinical targets and health outcomes across a wide variety of medical conditions. Adherence also majorly affects the cost-effectiveness of medications on a national scale.

For instance, a medication that is proven effective in clinical trials may be of reduced value, if patients are not adherent to it, which can be due to numerous reasons, including side effects or other negative characteristics that deter patients from taking it as prescribed.

Australia’s Pharmaceutical Benefits Scheme (PBS) provides a useful snapshot of dispatched medication that can be harnessed to deliver real-world evidence insights into medication utilisation, persistence and adherence trajectories on a national scale.

Dyslipidaemia is a prominent cardiovascular risk factor, with evidence showing that elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with a 70% increase in relative risk of cardiovascular mortality. Current lipid management guidelines recommend treatment with statins as first line treatment both for primary and secondary prevention of CVD but their effectiveness is dependent on the level of adherence and persistence.

Aim

The overarching aim of project involving analyses of PBS data is to explore the patterns of switching, adherence and persistence of lipid lowering therapies among the Australian general population and understand how general lipid lowering medication regimens are being adhered to in Australia.

Methods

A retrospective cohort study is generally conducted using a 10% of random sample of data from the PBS dataset. Switching, adherence to and persistence with medications are assessed; switching is defined as either switching to another intensity of medication or to another generic class agent. Non-persistence to treatment is generally defined as discontinuation (i.e. ≥90 days with no medication of interest) of coverage. Adherence is mainly measured using proportion of days covered (PDC), and patients with PDC < 0.80 are considered non-adherent.

Key findings to date

In the first phase of this project, we investigated the utilisation, adherence and persistence patterns of lipid lowering therapies in Australian general population and we have found that statins still remain the most prevalent lipid-lowering medication dispensed in Australia whereas dispensation of non-statin medications, such as ezetimibe and combination medication (i.e. statins and ezetimibe) and proprotein convertase subtilisin/kexin type 9 inhibitors, remains low. We also found that long-term persistence and adherence to statins remains generally poor, 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). In addition, we found that patients treated with lipid lowering therapy commonly experienced high frequency dispensing of multiple additional medicines. High rates were associated with older age, comorbidity and PBS concessional status and general beneficiaries frequently incurred significant cost.

Outputs

Talic S, Marquina C, Ofori-Asenso R, Petrova M, Liew D, Owen AJ, Lybrand S, Thomson D, Ilomaki J, Zomer E, Ademi Z. Switching, Persistence and Adherence to Statin Therapy: a Retrospective Cohort Study Using the Australian National Pharmacy Data. Cardiovascular Drugs and Therapy. 2022 Oct;36(5):867-877. doi: 10.1007/s10557-021-07199-7.
Talic S, Marquina Hernandez C, Ofori-Asenso R, Liew D, Owen A, Petrova M, Lybrand S, Thomson D, Ilomaki J, Ademi Z, Zomer E. Trends in the Utilization of Lipid-Lowering Medications in Australia: An Analysis of National Pharmacy Claims Data. Current Problems in Cardiology. 2022 Jul;47(7):100880. doi: 10.1016/j.cpcardiol.2021.100880.
Dunbar S, Liew D, Ilomaki J, Talic S. Overall medication burden for patients on lipid-lowering therapy: a cross-sectional analysis of national pharmacy dispensing data – under review.

Addressing the poor medication adherence in prevention of cardiovascular mort... View

Addressing the poor medication adherence in prevention of cardiovascular mortality and morbidity in Australia: development of a clinical decision support tool (phase 1)

Chief Investigators

Talic Stella, Ademi Delaney Zanfina, Liew Danny, Bell Simon, Reid Christopher, Green Sally, Ilomaki Jenni, Zomer Ella, Berkovic Danielle, Lybrand Sean, and Stratton Giles

Estimated completion date

31 May 2026

Background

Poor adherence to lipid lowering therapies is linked to significantly increased risk of cardiovascular events and death. Unfortunately, adherence to statins in Australia is far from optimal; with half of the patients not taking their medications as prescribed. Furthermore, nearly two thirds thirds of Australians failed to achieve national lipid management targets even after 24 months of statin therapy.

The growing burden of CVD on morbidity imposes financial stress on the national health resource, which funds millions of dollars for lipid lowering therapies annually. Given the well-established cumulative damaging effect of high LDL-C levels the impact of not adhering or delaying lipid lowering therapy directly leads to lost therapeutic benefit and a waste of resources.

This project will address critical evidence and knowledge gaps related to pharmacoepidemiology and risk of nonadherence to lipid lowering medications in Australian adults by harnessing the power of contemporary real-world data derived from primary health practices and supplemented by a qualitative exploration of patient, system, disease and clinical level factors. Given the current established link between nonadherence to LLM and CVD morbidity and mortality we aim that by addressing one of the most neglected risk factors (i.e. nonadherence to medications) we will be able to reduce the number of people developing CVD. This will enable us to develop tailored clinical decision support tool that identifies those that are likely to be nonadherent and integrates consumer developed and tailored prevention strategies to prevent further nonadherence related CVD morbidity and mortality.

Aims

Identify and assess risk factors associated with nonadherence and adherence to lipid lowering therapies in Australian adults in primary health practices.
Identify and evaluate patient, system, condition and therapy barriers and enablers to nonadherence to lipid lowering therapies.
Develop and evaluate a screening tool to identify individuals at highest risk of nonadherence to lipid lowering therapies so that prevention strategies can be timely and successfully actioned.
Develop an evidence-based clinical decision support tool incorporating preventative strategies for nonadherence to aid shared professional-patient decision making in addressing nonadherence to lipid lowering therapies.
Assess stakeholder acceptability of incorporating a clinical decision tool approach as part of key performance indicators for primary healthcare provision in Australia.

Methods

Project 1: A retrospective cohort study will be conducted to identify the types, trajectories and pathways of nonadherence, as well as comprehensive risk profile, in patients at risk of or with cardiovascular disease on lipid lowering therapies
Project 2: A qualitative exploratory study will be conducted to identify patients’ perspectives on barriers and enablers to adherence and reasons for poor/nonadherence.
Project 3: A full risk profile and risk prediction tool will be developed to aid in the identification of those at highest risk for nonadherence to lipid lowering therapies
Project 4: A Nominal Group Technique (NGT) study will be conducted to develop a decision support tool that include a set of preventative strategies that are tailored, feasible, sustainable and relevant for implementation in Australian primary health practices.
Project 5: A mixed-methods study will be conducted with primary health professionals and patients to assess acceptability, feasibility and ability to implement the decision support tool as part of key performance indicators for primary healthcare provision in Australia

Proposed outputs

C Nash, M Mortner, Trin C, I Buzancic, D Belec, N Evans, S Talic – Do clinical decision support tools improve quality of care outcomes in primary CVD prevention?: a systematic review and meta-analysis – ongoing
S Talic et al – Risk factors associated with nonadherence and adherence to lipid lowering terries in Australian adults in primary health practices: a retrospective cohort study – ongoing
S Talic et al – Barriers and enablers to adherence to lipid lowering therapies in primary CVD prevention: a qualitative study – ongoing
S Talic et al – Development of an evidence-based clinical decision support tool to address medication’s nonadherence – ongoing
S Talic et al – Stakeholder acceptability of incorporating the clinical decision tool to address medication’s nonadherence in for primary healthcare provision in Australia – ongoing

COMPLETED STUDIES

Lipid Optimisation Study (LOS) View

Lipid Optimisation Study (LOS)

Chief investigators

Danny Liew, Zanfina Ademi, Stella Talic, Ella Zomer, Clara Marquina, Sean Lybrand

This was a project under the mentorship of Prof Zanfina Ademi and Prof Danny Liew.

Background

In Australia in 2017, CVD accounted for 19% of the total burden of disease and was associated with 27% of deaths, more than 1 million hospitalizations, and accounted for 12% of the total health expenditure. Around 70% of CVD is attributable to modifiable risk factors, and strategies to target these range from population-wide public health programmes to individualised clinical interventions. Cardiovascular disease risk and prevalence is influenced by social determinants of health, including socioeconomic status. With increasingly stretched health system budgets, accurate prediction of the impact of CVD is needed to plan for efficient resource allocation and to deliver effective and sustainable strategies for disease prevention and management.

Aims

To understand the future burden of cardiovascular disease and its impact on health and economic outcomes in Australia, among the general population and also stratified across different socioeconomic groups. Also, to project the lost therapeutic benefit of delayed low-density lipoprotein cholesterol control in statin-treated patients, and assess the cost-effectiveness of lipid-lowering intensification.

Methods

Various methodologies were applied in this study including epidemiological and economic modelling, capturing both health and economic outcomes.

Key findings

We found that cardiovascular disease in Australia has substantial impacts in terms of morbidity, mortality, and lost revenue to the healthcare system and the society, and strategies to reduce cardiovascular health inequity are much needed. The modelling also demonstrated that delaying attainment of LDL-C goals translates into lost therapeutic benefit and a waste of resources.

Outputs

Marquina C, Talic S, Vargas-Torres S, Petrova M, Abushanab D, Owen A, Lybrand S, Thomson D, Liew D, Zomer E, Ademi Z. Future burden of cardiovascular disease in Australia: impact on health and economic outcomes between 2020 and 2029. European Journal of Preventive Cardiology. 2022 May 27;29(8):1212-1219. doi: 10.1093/eurjpc/zwab001.
Marquina C, Morton J, Zomer E, Talic S, Lybrand S, Thomson D, Liew D, Ademi Z. Lost Therapeutic Benefit of Delayed Low-Density Lipoprotein Cholesterol Control in Statin-Treated Patients and Cost-Effectiveness Analysis of Lipid-Lowering Intensification. Value in Health. 2023 Apr;26(4):498-507. doi: 10.1016/j.jval.2022.11.013.
Hastings K, Marquina C, Morton J, Abushanab D, Berkovic D, Talic S, Zomer E, Liew D, Ademi Z. Projected New-Onset Cardiovascular Disease by Socioeconomic Group in Australia. PharmacoEconomics. 2022 Apr;40(4):449-460. doi: 10.1007/s40273-021-01127-1.

Evaluation of LDL-C levels in lipid-lowering treated patients in Australia... View

Evaluation of LDL-C levels in lipid-lowering treated patients in Australia: the GP-EMR analyses

Background

Decades of research have established LDL-C as a causal factor in the development of atherosclerotic cardiovascular disease. Evidence from clinical trials have established statins as a cornerstone of treatment for dyslipidemia due to their ability to lower LDL-C and reduce risk of CVD. Yet controversies about the real-world clinical effectiveness of statins persist, especially in primary prevention settings.

Aims

This project explored general CV lipid management and epidemiology by understanding contemporary lipid management landscape in primary health practices. It also identified gaps in optimal lipid management and proposed optimisation strategies from clinical, public health and policy’s perspective.

Methods

Real World Evidence data extracted from electronic records from general practitioners across Australia that captures de-identified patient records was used. There is around 12% of the total primary care practices in Australia captured in this GP EMR dataset. The main outcome of interest was the proportion of patients achieving therapeutic LDL-C targets while on statin treatment. As per Australian lipid guidelines relevant to the study period, LDL-C target achievement was defined as ≤ 2 mmol/L for all risk groups

Key findings

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. In addition, combination therapy has been suggested as the new standard to achieve LDL-C goals, however most patients on combination therapy did not achieve LDL-C goals, representing lost therapeutic opportunity.

Outputs

Talic S, Marquina C, Zomer E, Ofori-Asenso R, Petrova M, Vargas-Torres S, Abushanab D, Wolfe R, Lybrand S, Thomson D, Stratton G, Liew D, Ademi Z. Attainment of low-density lipoprotein cholesterol goals in statin treated patients: Real-world evidence from Australia. Current Problems in Cardiology. 2022 Jul;47(7):101068. doi: 10.1016/j.cpcardiol.2021.101068.
Marquina C, Talic S, Zomer E, Vargas-Torres S, Petrova M, Wolfe R, Abushanab D, Lybrand S, Thomson D, Stratton G, Ofori-Asenso R, Liew D, Ademi Z. Attainment of low-density lipoprotein cholesterol goals in patients treated with combination therapy: A retrospective cohort study in primary care. Journal of Clinical Lipidology. 2022 Jul-Aug;16(4):498-507. doi: 10.1016/j.jacl.2022.05.002.
Talic S, Marquina C, Lybrand S, Liew D, Ademi Z. Calling for Urgent Actions to Improve Lipid Management in Australia-Low Medication Adherence and Poor Therapeutic Goal Attainment Lead to Poor Outcomes and Wasted Resources. Current Problems in Cardiology. 2023 Jul 27;48(12):102005. doi: 10.1016/j.cpcardiol.2023.102005.
C Trin, C Marquina, Z Ademi, S Talic S. Polypharmacy in patients on lipid lowering therapies and its association with liver and kidney function: a retrospective cohort study using primary care data – ongoing

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Centre of Cardiovascular Research and Education in Therapeutics

Medicine, Nursing and Health Sciences

Pharmacotherapeutics in Cardiovascular Disease Research Program

Theme leader

Dr Stella Talic

Key projects led by our team

ACTIVE STUDIES

Pharmacoepidemiological studies on utilisation, persistence and adherence of... View

Pharmacoepidemiological studies on utilisation, persistence and adherence of cardiovascular-related medications

Chief Investigators

Background

Aim

Methods

Key findings to date

Outputs

Addressing the poor medication adherence in prevention of cardiovascular mort... View

Addressing the poor medication adherence in prevention of cardiovascular mortality and morbidity in Australia: development of a clinical decision support tool (phase 1)

Chief Investigators

Estimated completion date

Background

Aims

Methods

Proposed outputs

COMPLETED STUDIES

Lipid Optimisation Study (LOS) View

Lipid Optimisation Study (LOS)

Chief investigators

Background

Aims

Methods

Key findings

Outputs

Evaluation of LDL-C levels in lipid-lowering treated patients in Australia... View

Evaluation of LDL-C levels in lipid-lowering treated patients in Australia: the GP-EMR analyses

Background

Aims

Methods

Key findings

Outputs