Dorairaj Prabhakaran

Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE): rationale and design of a randomised controlled trial of a cardiovascular preventive polypill-based strategy in India and Europe

The use of preventive medications in people at high risk of cardiovascular disease is conceptually straightforward, yet in practice the adoption of such measures is disappointingly low, plus there is wide international variation in preventive therapies. Several barriers might explain this shortfall and variation, but the simplicity and economy of a polypill-based strategy might overcome some barriers. The ‘Use of a Multidrug Pill In Reducing cardiovascular Events’ (UMPIRE) trial assesses whether a polypill strategy (by combining aspirin, a statin and two blood pressure lowering agents) would improve adherence to guideline-indicated therapies and would lower both blood pressure and cholesterol, in people with established cardiovascular disease. UMPIRE, running in India and three European countries (England, Ireland and the Netherlands), is an open, randomised, controlled trial designed to include 1000 participants in India and 1000 in Europe, with a followup of 12–24 months. Participants were randomised to one of two versions of the polypill or relegated to usual care. The primary study outcomes were the self-reported use of aspirin, a statin and at least two blood pressure lowering agents; as well as changes in blood pressure and cholesterol. Secondary outcomes included: any cardiovascular events, reasons for stopping medications, serious adverse events and perceived changes in quality of life. Interpretation of the study data will be enhanced by health, economic and process-related evaluations. UMPIRE is registered with the European Clinical Trials database, as EudraCT: 2009-016278-34 and the Clinical Trials Registry, India as CTRI/2010/091/000250. The trial was part of the ‘Single Pill Against Cardiovascular Events (SPACE)’ collaboration, which encompasses the ‘IMProving Adherence using Combination Therapy (IMPACT)’ and ‘Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)’ trials.

Relationships among Major Risk Factors and the Burden of Cardiovascular Diseases, Diabetes, and Chronic Lung Disease

Cardiovascular, respiratory, and related disorders (CVRDs) are a subset of noncommunicable diseases (NCDs) that are an important and increasing cause of morbidity and mortality in lowand middle-income countries (LMICs). CVRDs share common risk factors such as smoking, poor diet, and physical inactivity. They also share common interventions at the clinical, public health, and policy levels. Public health professionals and decision makers share a widespread notion that CVRDs are diseases of the affluent (WHO 2010b). Yet recent cross-national studies have demonstrated that the burden of CVRDs falls disproportionately on lower-income countries and disadvantaged groups within countries. Prevention and control of CVRDs, then, have important equity implications. Addressing CVRDs also fits in with the Sustainable Development Goals that focus on reducing poverty and improving health, particularly through mechanisms (such as universal health coverage) that can address the rise in CVRD risk factors and the potential impoverishing effects of chronic illness. The concept that current or past exposure to specific factors increases the risk of future ischemic heart disease (IHD) was first established in the Framingham Heart study in the United States (Kannel and others 1961), but it has been validated extensively in LMICs (O’Donnell and others 2010; Yusuf and others 2004). These risk factors are now well established globally, not only for IHD (Pearson and others 2003; Perk and others 2013; Yusuf and others 2001; Yusuf and others 2004), but also for stroke (Colditz and others 1988; Markus 2011; O’Donnell and others 2010), other cardiovascular diseases (CVDs) (Greenland and others 2010; Khatibzadeh and others 2013; Mosca and others 2004; Smith and others 2011), diabetes (Caballero 2003; Singh and others 2010; Weber and others 2012; Zimmet and others 1999), chronic lung disease (Madison, Zelman, and Mittman 1980; Palta and others 1991; Salvi and Barnes 2009; Strope and Stempel 1984), and other chronic NCDs (Allender and others 2011; Ezzati and Riboli 2013; Hallal and others 2012). Exposure to these risk factors may occur early in life, including in utero, and continue throughout life or may be limited to only certain phases of the life span. These risk factors may be strongly influenced by socioeconomic and environmental determinants, policy and legislative interventions, lifestyle and behavioral choices, and familial and genetic predisposition. Among modifiable risk factors, reducing the level of individual or population