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Secondary prEvention of CardiovascUlaR disease in the Elderly trial

Periodic Reporting for period 4 - SECURE (Secondary prEvention of CardiovascUlaR disease in the Elderly trial)

Reporting period: 2019-11-01 to 2021-04-30

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.

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. 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 Spain, Italy, France, Germany, Hungary, Poland and Czech Republic.
During the first period of SECURE partners prepared the start of the trial. The required documents and the clinical protocol were submitted and approved in all countries. The SECURE database was also set up. In addition, the polypill was produced, labelled, packaged and shipped to the study centres. In August 2016, the clinical trial started.

During the second period, work was focused on the recruitment of patients, and also included:
- Hiring and managing subcontractors
- Managing FDC to ensure normative compliance
- Compliance with ICH-GCP, GMP and local Guidelines
- Pharmacovigilance
- Managing 115 hospitals across 7 countries.

In addition, the two initial DSMBs (Data Safety Monitoring Board) meetings where organized. This independent committee is key to guarantee the usefulness and effectiveness of the trial.

During the third period, SECURE partners were pursuing the recruitment of participants within the 7 countries. Importantly, a 20-month extension of the Trial was granted by the EC to ensure an increase FU of participants and reinforce the statistical significance of the data obtained. In addition, two updates of the trial documents were submitted through the VHP standardized procedure. The third DSMB meeting was organized. The SECURE database was activated for the Clinical Events Committee’s work.

During the fourth period, the recruitment of patients finalized in all countries, being Spain, Italy and Germany the last countries to recruit new participants up to 31st of December 2021. Thus, all sites were involved in the Follow-Up (FU) of the participants. Then, in March 2020 the COVID-19 pandemic became a major issue in all Europe, affecting all the sites and countries involved in the Trial and threatening to jeopardize the future outcome of SECURE. Thanks to a quick and fluent communication among partners and with the EC, a battery of corrective measures were placed both to guarantee the safety of SECURE participants and ensure the proper development of the trial. (see table 2.2 below). The SECURE trial has continued in all sites and countries. In addition, the pollypil has been supplied to the centers, that eventually have activated its delivery to the participants at decision of the local physician. The SECURE partners have continued to hold regular meetings, including the Annual Meeting, two quarterly meetings among partners and individual meetings of the Coordinator with every partner every 6-8 weeks.

SECURE partners have been also performing dissemination activities. A public website was set up and a brochure that was translated into the 7 languages of the countries involved. A roll-up banner was also produced to be used during events attended by SECURE partners. SECURE has been presented in international events in the field, notably during the last five 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. In addition, the pollypil received in October 2018 an OAT award as the best project on multidisciplinary adherence. Finally, on February 2020 SECURE delegates attended a meeting organized by the GLORIA Trial that hosted representatives of the six RCTs funded in the same call than SECURE (with 7612 elderly patients currently enrolled in 20 countries), and compiled lists of potential barriers and solutions in trials dealing with elder population. This work is now accepted to be published in Age & Aging journal and will be presented in the ACR Convergence 2021 meeting.
The results of the SECURE trial could potentially have profound impact on secondary cardiovascular prevention in the elderly population 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 the first trial to address the efficacy of the FDC on CV outcomes in secondary prevention in the elderly population. 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 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, as these demographic changes are mirrored in most of the rest of the world, 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.
SECURE Polypill