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Secondary prEvention of CardiovascUlaR disease in the Elderly trial

Periodic Reporting for period 3 - SECURE (Secondary prEvention of CardiovascUlaR disease in the Elderly trial)

Reporting period: 2018-05-01 to 2019-10-31

While Cardiovascular diseases (CVD) are the main cause of death worldwide, they are responsible for half of all deaths in Europe. The overall ageing of the European population and improving survival of patients with coronary heart disease has created a large population of older adults eligible for secondary prevention. Despite the established efficacy of cardiovascular medications, suboptimal adherence reduces their effectiveness and is the primary reason for suboptimal clinical benefit, contributing significantly to worsening of diseases and deaths at the population level.
SECURE is the first trial testing the efficacy of a fixed dose combination (FDC) polypill for secondary cardiovascular prevention in the elderly population (≥ 65 years old). The main objective is to evaluate the potential benefit of the FDC as a component of a cost-effective, globally available and comprehensive treatment strategy for secondary prevention of cardiovascular events as compared to standard therapy (the three components of the polypill given separately). As part of the secondary endpoints, SECURE will compare the effect of both strategies on adherence and intermediate measures of risk factor control such as lipids and blood pressure. Importantly, it will also measure the pharmacoeconomic impact of the FDC intervention as well as regional differences in all outcomes. The project involves subjects from seven countries: Spain, Italy, France, Germany, Hungary, Poland and Czech Republic.
During the first 18 months of the SECURE project, partners have prepared the start of the clinical trial. Study sites were selected in all 7 countries involved. The required documents and the clinical protocol were finalised and submitted to the Ethics Committees and Competent Authorities. The first major achievement of this period was to obtain the necessary approvals in all countries. In parallel, partners prepared contracts with the hospitals selected, activating the sites and training the investigators. The SECURE database was also set up. In addition, the polypill to be used as treatment was produced, labelled, packaged and shipped to the study centres. In August 2016, the clinical trial started.

During the following 18 months, work was focused on the recruitment and follow-up of patients for the clinical study and consisted in:
• Tracking recruitment performance and designing strategies to boost recruitment
• Hiring and managing subcontractors
• Managing FDC drug supplies, expiration dates, destruction from all participating hospitals to ensure compliance to the national and local normative
• Ensuring the project complies with ICH-GCP, GMP and local Guidelines
• Focusing on the pharmacovigilance of the trial to ensure patient safety and proper surveillance of the trial
• Selecting, opening, and managing over nearly 115 sites across 7 countries.

During the last 18 months, SECURE partners have been pursuing the recruitment of participants within the 7 countries. In addition, two updates of the trial documents were submitted through the VHP standardized procedure.
The third DSMB (Data Safety Monitoring Board) meeting was organized in October 2018. This independent committee is key to guarantee the usefulness and effectiveness of the trial. Its report has been very positive and strongly advised to continue with the trial. The SECURE database is being maintained for the Clinical Events Committee’s work, and the first event adjudication is now ongoing.

While the scientific activities of the project were progressing, SECURE partners have been performing dissemination activities to raise awareness of the project. A public website was set up at the beginning and a brochure was produced one year later. This leaflet was also translated into the 7 languages of the countries where the study takes place. A roll-up banner was also produced to be used during events attended by SECURE partners. The project was presented during many international events in the field of cardiovascular diseases and prevention, notably during the last five ESC (European Society of Cardiology) Congresses. In addition to 7 peer-reviewed publications and one press release on the EU website, the partners published several articles on their websites and in relevant journals. The internal management of the project was also ensured through the set-up of the necessary collaboration tools and regular telephone meetings.
The results of the SECURE trial could potentially have profound impact on secondary cardiovascular prevention in the elderly population in different EU countries as it will provide:
• The proof of concept of the efficacy and cost-effectiveness of an FDC polypill for secondary CV prevention and treatment over traditional therapies.
• Understanding the impact of a polypill strategy on adherence to CVD treatment.
• Recommendations on how to address major challenges related to effective secondary CV prevention: adherence, risk factor control, access to treatment and health care utilisation and costs related to the aforementioned.
SECURE is be the first trial to address the efficacy of the FDC on CV outcomes in secondary prevention in the elderly population. Measuring and comparing the effect of both strategies on health care resource utilisation and costs will help design more efficient interventions tailored to meet the specific challenges of secondary prevention in different European countries.
The findings and conclusions obtained in SECURE will allow the drafting of clinical guidelines and recommendations that will provide useful guidance and will serve as a reference framework for all stakeholders involved. Furthermore, SECURE will provide necessary data to address the critical issue of secondary prevention of CV disease in LMICs (Low and Middle Income Countries), where a FDC polypill strategy could prove useful to address several problems that limit the effectiveness of secondary prevention strategies: inadequate health policies, poor availability, and lack of affordable medication.
The SECURE consortium partners strongly believe that the present study is necessary in order to effectively tackle the CVD epidemic that is taking place worldwide. The demographic changes taking place in Europe will mean that ever increasing numbers of people will live longer and that an increasing proportion of this elderly population will be subject to secondary CV prevention. Currently we have access to very effective pharmacologic and non-pharmacologic interventions for CV prevention in Europe, but their efficacy on the control of the disease growth is limited, mainly due to non-adherence. Moreover, health care costs have continued to rise throughout Europe. The polypill concept is an attractive and imaginative idea that can significantly improve CV prevention and improving patient adherence to treatment, and therefore lowering costs. Importantly, these demographic changes are mirrored in most of the rest of the world. Hence, the extrapolation of the data and application of the potential benefit of the polypill in LMICs countries could have an impact on sparing millions of lives.
In this context, the publication of the PolyIran Study has provided solid proof of concept evidence that the polypill is superior to the alternative standard multipill regimen in lowering outcome cardiovascular events, which is a huge step forward in supporting global implementation of the polypill as an effective alternative.
Recruitment goal in the 7 countries enrolling patients for SECURE