Authors' objectives: BACKGROUND: Cardiovascular disease (CVD) is ranked as the number one cause of mortality and is a major cause of morbidity worldwide. High blood cholesterol is linked to CVD events. In addition to lifestyle optimization, statins are the first-choice treatment to reduce high blood cholesterol and consequently prevent CVD events. The clinical– and cost-effectiveness of primary prevention of CVD using statins in low or medium risk populations is a topic of debate. OBJECTIVE: The aim of the HTA is to investigate the clinical efficacy, effectiveness, safety, and cost-effectiveness (covering all HTA domains) of statins compared to no treatment (including lifestyle adaptations) in primary prevention of CVD in certain CVD risk groups.

Authors' results and conclusions: RESULTS: Evidence from two high quality systematic reviews including data of 37 randomized controlled trials (RCTs) informed the HTA domains efficacy and safety of statin therapy for primary prevention of CVD in adults. Two high quality non-randomised studies provided additional data on effectiveness and safety. No studies were found on the efficacy of lifestyle adaptations (in combination with statin therapy) for primary prevention of CVD in adults. Statin therapy showed to be effective in the prevention of cardiovascular events and mortality in adults without established CVD. The available data from non-randomised studies was too scarce to draw conclusions on the effectiveness of statins. In most studies, treatment with statins did not result in an increased risk of adverse events. Statin use only resulted in a significant risk increase for hepatic dysfunction (low quality of evidence) and renal dysfunction (moderate quality of evidence). However, there are limitations regarding the definitions of these outcomes in the RCTs. The available evidence for the adverse event myalgia was inconsistent. Although the comparative evidence for safety is inconclusive, the adverse event rate of using statins was low. No evidence of efficacy, effectiveness, or safety for the different CVD risk groups (low, medium and high) could be presented as risk scores for CVD were hardly reported in the studies. Results from the de novo economic model showed that from a healthcare payers perspective, applying a lifetime time horizon with discounting, and assuming real-world treatment adherence and no discontinuation due to adverse events, statin therapy for primary prevention of CVD seems to be associated with low ICERs compared to no statin therapy in subgroups with a low, moderate or high CVD risk (i.e. an AGLA risk above 1%), especially for those at younger age and females. ICERs were higher in subgroups with low CVD risk (expressed in AGLA risk), older age and in males. The scenario and sensitivity analyses showed that a shorter time horizon, applying a higher discount factor, and reduced treatment adherence increased the ICERs significantly. In addition, the effectiveness of statins in reducing CVD events, the proportion of MI versus CVD deaths, and the costs of statin therapy were important parameters that introduced uncertainty about the cost-effectiveness of statin therapy. Due to a lack of data on the current use of statins for primary prevention of CVD in various CVD risk groups in Switzerland, the budget impact of restricted reimbursement policies compared to the current unrestricted use of statins in Switzerland could not be determined. Instead, the maximum population-level annual healthcare costs of reimbursement policies were estimated assuming all eligible patients would use statins with real-world adherence. The annual costs of reimbursing statin therapies, from a healthcare payers perspective in the Swiss context, ranged from 934 million CHF in case all low, moderate, high and very high risk individuals were to be treated with statins to approximately 4 million CHF in the most restricted reimbursement policy where statin therapies were only reimbursed for people between 60 and 75 years old at high CVD risk. Relevant legal, social, ethical, and organisational issues identified included that changes in reimbursement policy can further increase health disparities between patients based on sex, race, and socioeconomic status and that real-world adherence to statins differs greatly from adherence in a clinical setting, especially in case of primary prevention. CONCLUSION: Sufficient evidence shows that statin therapy prescribed to adults without established CVD is effec-tive in the prevention of cardiovascular events and mortality under study conditions (i.e. efficacy), but there is limited evidence on safety and effectiveness under real-world settings. Risk scores for CVD were hardly reported in the studies and no stratification of the efficacy, effectiveness, or safety results was available for people with low, medium, or (very) high CVD risk. Statins can prevent CVD events in patients without CVD without many adverse events at a reasonable cost, especially in subgroups with an AGLA risk score above 1% The cost-effectiveness of statin therapy is highly dependent on model settings and uncertain input parameters. Furthermore, as there is no data on the current use of statins for primary prevention of CVD events in Switzerland, the exact cost savings of disinvestment in statin therapies for the national healthcare budget remain unclear.

Authors' methods: METHODS: Systematic literature searches were performed in PubMed (MEDLINE) and Embase to identify relevant published evidence for the HTA domains. For the clinical and cost-effectiveness domains, data was extracted from the included studies in predefined evidence tables and summary tables were made for different study types. For the other domains (including ethical, legal, social, and organisational issues), the evidence was described narratively. The preliminary literature search on the cost-effectiveness of statins for primary prevention of CVD in Switzerland did not provide sufficient evidence. Therefore, a de novo cost-effectiveness Markov model was developed, characterising the natural history of the disease in a patient’s lifetime in the Swiss clinical practice. This cost-effectiveness model was used to determine the cost-effectiveness of statin therapy versus no statin therapy for primary prevention of CVD applying a lifetime time horizon, discounting of costs and effects with 3%, and assuming real-world adherence (69% in year 1, 60% in subsequent years). The uncertainty around input parameters was explored in sensitivity and scenario analyses. In addition, the maximum annual population-level healthcare costs assuming real-world adherence were estimated.

Project Status: Completed

URL for project: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-projekte/statine.html

Year Published: 2021

URL for published report: https://www.bag.admin.ch/dam/bag/en/dokumente/kuv-leistungen/leistungen-und-tarife/hta/berichte/h0032chol-hta-report.pdf.download.pdf/h0032chol-hta-report.pdf

URL for additional information: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-programm.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Switzerland

Organisation Name: Swiss Federal Office of Public Health (FOPH)

Contact Address: Federal Office of Public Health, Schwarzenburgstrasse 157, CH-3003 Berne, Switzerland

Contact Name: Stephanie Vollenweider

Contact Email: hta@bag.admin.ch

Copyright: Swiss Federal Office of Public Health