Role of the polypill for secondary prevention in ischaemic heart disease.

In 2011, for the first time in the history of humankind, non-communicable diseases became the leading cause of death worldwide. This change in trend is obviously multifactorial and very complex, as it is the paradoxical result of social, economic and health system growth worldwide. Vaccination and infectious diseases control, changing dietary habits worldwide, sedentary behaviour, globalisation, industrialisation (resulting in a shift from manual to sedentary labour), tobacco and sugary beverage surges in low- and middle-income countries and rapid urbanisation have all played a role in this epidemic transition. At the same time, the increase in cardiovascular risk factors, together with a decline in mortality in high-income countries in the past two decades, has led to a significant upsurge in the prevalence of secondary prevention of ischaemic heart disease. With this, the effect that non-adherence to cardioprotective drugs is having has become progressively clear, both in terms of clinical outcomes and as a driver of increased healthcare expenditure. The cardiovascular polypill, which was originally proposed as a strategy to improve accessibility to cardioprotective drugs worldwide, has proven to be a mainstay therapeutic approach for improving medication adherence in cardiovascular disease. In the current paper, we aim to review the need for a polypill strategy in the present scenario of cardiovascular disease, the available data that support such a strategy and the various clinical trials that are in progress that will help further shape future indications for the cardiovascular polypill.

Putting polypills into practice: challenges and lessons learned.

Regulatory approvals for cardiovascular polypills are increasing rapidly across more than 30 countries. The evidence clearly shows polypills improve adherence and cardiovascular disease risk factors for patients with indications for use of polypill components-ie, those with established cardiovascular disease or at high risk. However, the implementation of polypills into clinical practice has many challenges. The clinical trials literature provides insights into the clinical impact of a polypill strategy, including cost-effectiveness, safety of use, substantial improvement in adherence, and better risk factor control than usual care. Despite the clear need for such a strategy and the available clinical data backing up the use of the polypill in different patient populations, challenges to widespread implementation, such as an absence of government reimbursement and poor physician uptake (identified from on the ground experience in countries following commercial rollout), have greatly obstructed real-world implementation. Obtaining the full public health benefit of polypills will require education, advocacy, endorsement, and implementation by key global agencies such as WHO and national clinical bodies, as well as endorsement from governments.

Optimal pharmacological treatment and adherence to medication in secondary prevention of cardiovascular events in Spain: Results from the CAPS study.

INTRODUCTION: Despite the large amount of evidence supporting the use of antiplatelet agents, beta-blockers, angiotensin antagonists, and lipid-lowering statins in patients with stable coronary artery disease, several studies have documented underprescription of optimal medical treatment (OMT) in Spain. AIMS: The present study aimed to describe the current trend of pharmacological prescription in secondary prevention treatment for cardiovascular diseases (CVDs) in a Spanish cohort. METHODS: This study was a multicenter, observational, cross-sectional study (CAPS study, FER-CAR-2014-01) in the context of only one visit. Adherence levels to the prescribed medication, the reasons for not prescription of each medication, the existence of possible associations between sociodemographic features, different CVDs, and different drugs with treatment compliance were also analyzed in patients who have suffered cardiovascular effects. RESULTS: Six hundred and twelve patients (68.5±10.7 years old; 78% males) were included. OMT was prescribed in 40.8% of the patients. The main reason for not prescribing was due to the physician's discretion. Adherence to medication, measured by the Morisky-Green questionnaire, was 45.8%, and it was positively related to the presence of coronary events (OR 1.80; 95% CI: 1.05-3.21) but not with any drug type. Moreover, a higher educational background implied a higher percentage of adherence to medication. Finally, nonadherent patients were prescribed more daily medicine intakes. CONCLUSIONS: Low adherence to guideline-oriented treatment as well as low adherence to medication was found by a self-reported questionnaire. Enhancing adherence to guideline-recommended therapy and reducing treatment complexity seem to be reasonable strategies to improve adherence to secondary prevention medications.

Global burden of CVD: focus on secondary prevention of cardiovascular disease.

Despite encouraging advances in prevention and treatment of atherothrombosis, cardiovascular disease (CVD) remains a major cause of deaths and disability worldwide and will continue to grow mainly due to the increase in incidence in low and middle income countries (LMIC). In Europe and the United States of America (USA), coronary heart disease (CHD) mortality rates have decreased since the mid-1990s due to improvements in acute care, however the prevalence of CHD is increasing largely in part due to the overall aging of the population, increased prevalence of cardiovascular (CV) risk factors, and improved survival of patients after a CV event. Data from clinical trials has consistently proven the efficacy of pharmacologic interventions with aspirin, statins, and blood pressure (BP)-lowering agents in reducing the risk of CV events and total mortality in the ever growing pool of patients in secondary prevention. However, large gaps between indicated therapy and prescribed medication can be observed worldwide, with very low rates of use of effective therapies in LMIC countries. Adherence to medication is very poor in chronic patients, especially those treated with multiple pharmacologic agents, and has been directly correlated to a greater incidence of recurrent CV events and increase in direct and indirect healthcare costs. In this article, we review the global burden of CV disease, status of secondary prevention therapy and major barriers for treatment adherence.

The Fuster-CNIC-Ferrer Cardiovascular Polypill: a polypill for secondary cardiovascular prevention.

During the last decade, there has been a tremendous effort to develop different cardiovascular polypills in response to the upsurge in global cardiovascular disease worldwide. The pharmacological development of such a strategy has proven to be extremely complex from a formulation standpoint. Not all drugs are suitable for use in a polypill because of potential drug incompatibilities between them. Candidate agents must be safe, well tolerated, effective, guideline recommended and physiochemically compatible with the other components of the pill. The Fuster-CNIC-Ferrer cardiovascular (CV) polypill has been found to be the first-in-class polypill to be approved and commercialized in Europe and Latinamerican Countries. In this article, we review the pharmacological properties of its three components, including the clinical evidence supporting their use in patients with established cardiovascular disease, their pharmacokinetic properties, adverse effects, drug interactions and contraindications.

The cardiovascular polypill: clinical data and ongoing studies.

Cardiovascular risk modification in terms of comprehensive medical therapy (antithrombotic therapy, lipid-lowering therapy, antihypertensive medication) and lifestyle modification (healthy diet, regular exercise, weight loss, smoking cessation) is the cornerstone of secondary prevention. It is now clear that even in those undergoing PCI or bypass surgery, appropriate lifestyle modification and aggressive medical therapy are paramount for optimizing long-term outcomes. However, what has emerged from studies that examined the role of medical therapy in the context of coronary heart disease is that only ∼50% of the patients in these studies are achieving target treatment goals for blood pressure, lipid and glycemic control. Non-adherence is thought to be a very large contributor to this problem; across all health-care categories, non-adherence is estimated to account for $290 billion of annual health-care expenditure in the United States and €1.25 billion in European Union, with poor adherence to CVD medication accounting for 9% of all European CVD events. Socioeconomic factors may have a role in patients' discontinuing their medications, and a major initiative to combat this problem is the increasing focus on the polypill. The idea of combining numerous medications into a single tablet to reduce CV risk was first proposed more than a decade ago. This combined formulation not only significantly enhances patient convenience and adherence but also drives savings for the healthcare systems. Several randomized clinical trials have consistently demonstrated the effects of polypills on CV risk factors and adherence, and major trials are underway to study the effect on hard clinical outcomes.

Promoting cardiovascular health worldwide: strategies, challenges, and opportunities.

Cardiovascular disease is the leading cause of death in the world, affecting not only industrialized but, above all, low- and middle-income countries, where it has overtaken infectious diseases as the first cause of death and its impact threatens social and economic development. The increased prevalence of cardiovascular disease in recent years together with projected mortality for the coming decades constitute an irrefutable argument for the urgent implementation of well-planned interventions to control the pandemic of cardiovascular diseases, especially in the more economically deprived countries. The combination of behavioral, social, environmental, and biological factors, and others related to health care systems, that contribute to the development of cardiovascular diseases requires a multi-sector strategy that promotes a healthy lifestyle, reduces cardiovascular risk factors, and cuts mortality and morbidity through quality health care services. These proposals should be guided by leaders in the scientific community, government, civil society, private sector, and local communities.

The relationships between cardiovascular disease and diabetes: focus on pathogenesis.

There is a looming global epidemic of obesity and diabetes. Of all the end-organ effects caused by diabetes, the cardiovascular system is particularly susceptible to the biologic perturbations caused by this disease, and many patients may die from diabetes-related cardiovascular complications. Substantial progress has been made in understanding the pathobiology of the diabetic vasculature and heart. Clinical studies have illuminated the optimal way to treat patients with cardiovascular manifestations of this disease. This article reviews these aspects of diabetes and the cardiovascular system, broadly classified into diabetic vascular disease, diabetic cardiomyopathy, and the clinical management of the diabetic cardiovascular disease patient.

Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review.

Ewing's sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing's sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing's sarcoma into "good" and "poor" responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing's sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients.