Polypill/FOCUS

The prevention of cardiovascular disease is hindered by several factors, including wide variability in the pattern of prescription among physicians, limited access to expensive drugs in emerging countries, and poor adherence to medication. The use of fixed dose drug combinations (polypill) has been recommended to improve accessibility and adherence to treatment. The CNIC, working in a private-public partnership with Ferrer International, has devised a fixed dose combination for secondary prevention. The CNIC-Ferrer polypill project is led by Valentín Fuster and is coordinated by the Translational Research Platform.

During the last year we have conducted several clinical trials to ensure the quality and safety of the polypill. A new study to explore the potential pharmacodynamic interactions with simvastatin was launched in Spain. The kick-off meeting of the FOCUS project, which tests the fixed-dose combination concept for cardiovascular prevention in populations with different socio-economic characteristics, was held in Madrid in June 2011. Patient recruitment began during the first half of 2011. An important aim of FOCUS is to increase understanding of the factors that determine poor treatment adherence and inappropriate prescribing for secondary cardiovascular prevention. This will allow FOCUS to establish recommendations for better use of medication in patients with ischemic heart disease. After the successful completion of FOCUS, secondary prevention medication will be available and affordable for large numbers of patients in developed and developing countries.

We are very excited by this project, since we believe that FOCUS will help to determine the role that the polypill can play in cardiovascular disease prevention and will enable recommendations to be established for the better use of medication in patients with ischemic heart disease.

Why a polypill for secondary prevention?

The past century witnessed major advances in the understanding, prevention and treatment of atherothrombosis and its clinical manifestations: stroke and ischemic heart disease. We have now very effective interventions to control risk factors, and the incidence and mortality of CV diseases is actually decreasing in some industrialized countries. In spite of these encouraging developments, the global burden of cardiovascular disease is increasing steadily, and these conditions remain the first cause of death worldwide. The burden of disease is increasing mainly in low and middle income countries, where it dis twice that of malaria, AIDS and tuberculosis put together.

There are several reasons for the lack of success of cardiovascular prevention policies. The most important reasons are inadequate prescription, lack of availability and non-affordability of medication in low and middle income countries, and poor adherence to healthy life styles and medical therapy. The idea of a fixed dose combination pill for cardiovascular prevention was first proposed by several authors at the beginning of the present century and has been supported by the WHO.

Wald and Law further developed the polypill concept in a seminal paper, published in the BMJ in 2003, which opened up a wide debate on the value of the polypill concept. The authors argued that a single polypill containing six active components and administered to all individuals older than 55 would improve cardiovascular prevention by facilitating adherence to treatment, avoiding the need for multiple medical contacts and reducing cost. During the last few years this concept, particularly in the field of primary prevention, has been questioned by some experts. However, the potential role of a polypill for secondary cardiovascular prevention is receiving increasing attention. In this regard, a recent report from the World Health Organization entitled Medicines for Europe and the World stated that "It is strongly recommended that a research agenda should be established to produce and test fixed dose combination (FDC) products for secondary prevention of heart attack and stroke to improve adherence and prevent mortality and morbidity".

The CNIC-FERRER polypill (TrinomiaR)

The following milestones have been successively achieved: drug and dose selection, Galenic formulation, preclinical studies and pharmacokinetic-bioequivalence studies. TrinomiaR is now undergoing registration in countries in Central and South America, and has been commercially available in Guatemala since last February.

Others polypills for CV prevention

Several companies, most of them located in India, are developing polypills for cardiovascular prevention. The majority of these polypills address primary prevention. Dr. Reddy, a large Indian pharmaceutical company, is developing a polypill for secondary prevention, which is being tested in the UMPIRE study, also funded by the 7th Framework Programme. Unlike the UMPIRE study, the FOCUS project, in addition to testing the efficacy of the polypill in terms of patient adherence, will pay special attention to the psychosocial and economic factors related to poor prevention.