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Secondary prEvention of CardiovascUlaR disease in the Elderly trial

Periodic Reporting for period 5 - SECURE (Secondary prEvention of CardiovascUlaR disease in the Elderly trial)

Reporting period: 2021-05-01 to 2021-12-31

While Cardiovascular diseases (CVD) are the main cause of death worldwide, they are responsible for half of all deaths in Europe. The 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.
A polypill strategy including antiplatelet, lipid lowering and blood lowering treatments has been proposed as a simple approach to reduce cardiovascular morbidity and mortality. SECURE aimed to assess the effectiveness and safety of a three component polypill including aspirin 100mgs, atorvastatin 20mg or 40mgs, and ramipril 2.5 mgs, 5mgs or 10mgs, as compared to usual care in reducing major adverse cardiovascular events in elderly post myocardial infarction patients.
SECURE is a randomized, un-blinded, controlled, 2-group, parallel, multinational trial. 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 compares the effect of both strategies on adherence and intermediate measures of risk factor control. Importantly, it also measures 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.
In this trial we have shown that Polypill treatment is an effective approach in secondary prevention in the elderly. In particular, we demonstrated that the use of a cardiovascular polypill as a substitution approach, namely to use the polypill in patients already taking cardio protective drugs for secondary prevention, should be an integral part of the preventive strategy to reduce mortality and morbidity worldwide.
During the first period, partners submitted the trial documents and got the approval in all countries. The database was also set up. The polypill was produced, labelled, packaged and shipped to the centres. In August 2016, the trial started.
During the following periods, work was focused on the recruitment of patients, managing 113 hospitals across 7 countries.
During the fourth period, the recruitment of patients finalized, being Spain, Italy and Germany the last countries to recruit new participants up to 31st of December 2021. Then, in March 2020 the COVID-19 affected all the sites and countries involved in the Trial. A battery of corrective measures were placed both to guarantee the safety of participants and ensure the proper development of the trial. In addition, a total of 5 Data Safety Monitoring Board meetings where organized. This independent committee is key to guarantee the usefulness and effectiveness of the trial
Finally, during the last period, partners finalized the follow-up of the patients. Close monitoring activities and pharmacovigilance were maintained to ensure data quality and patient safety. The database has been depurated to maximize data homogeneity. In addition, the Statistical Analysis Plan of the trial was approved.
The results of the trial have been presented at the “Late-Breaking Trial” session of the European Society of Cardiology Congress. In addition, the main paper containing the main results of the trial has been published in one of the most prestigious journal of the field, the New England Journal of Medicine (Polypill Strategy in Secondary Cardiovascular Prevention. NEJM August 26, 2022; DOI:10.1056/NEJMoa2208275 https://www.nejm.org/doi/full/10.1056/NEJMoa2208275?query=featured_home).
Other actions of dissemination have been performed. In addition, the pollypil received in October 2018 an OAT award as the best project on multidisciplinary adherence.
The results of the SECURE trial could have profound impact on secondary cardiovascular prevention in the elderly population in Europe as it provides:
s The proof of concept of the efficacy and cost-effectiveness of an FDC polypill for secondary CV prevention and treatment over traditional therapies.
s Understanding the impact of a polypill strategy on adherence to CVD treatment.
s 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.
Measuring and comparing the effect of both strategies on health care resource utilisation and costs will help design more efficient interventions to meet the challenges of secondary prevention in Europe.
The findings and conclusions obtained in SECURE will allow the drafting of clinical guidelines and recommendations that will serve as a reference framework for all stakeholders involved. Furthermore, SECURE will provide necessary data to address secondary prevention of CVD in LMICs (Low and Middle Income Countries), where a FDC polypill strategy could prove useful to address several problems of secondary prevention strategies: inadequate health policies, poor availability and lack of affordable medication.
The demographic changes taking place in Europe will mean that 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 is limited mainly due to non-adherence. Moreover, health care costs have continued to rise throughout Europe. 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.
At SECURE, a total of 2499 patients were randomized with a median follow up of 36 months. The primary outcome occurred in 118 (9.5%) participants in the polypill group compared with 156 (12.7%) in the usual care group (hazard ratio (HR) 0.76; 95% CI 0.60 to 0.96 p=0.02). The key secondary outcome occurred in 101 participants (8.2%) in the polypill group and in 144 participants (11.7%) in the usual care group (HR 0.70; 95% CI, 0.54 to 0.90). The results were consistent across prespecified subgroups. Patients randomized to the polypill arm showed higher levels of adherence. Adverse events were similar between in both groups.
In the present trial, a treatment strategy based on a polypill containing aspirin, atorvastatin, and ramipril, led to reductions in recurrent cardiovascular events following MI in elderly patients. The use of a cardiovascular polypill as a substitution approach, namely, to use the polypill in patients destined to take cardiovascular drugs effective in secondary prevention, could be an integral part of a preventive strategy. The rational is straightforward: by simplifying treatment complexity, improving availability and efficiency, the polypill might serve as a widely applicable strategy to improve accessibility to treatment, adherence and ultimately decrease the risk of recurrent disease and death at a global scale.
SECURE Polypill