CVD prevention can be addressed at three levels – primordial, primary, and secondary.

Primordial prevention aims at preventing the development of risk factors in people and generally operates at the community or population level. Thus, in CVD prevention, the objective of primordial prevention would be prevention of tobacco use and reduction of mean population blood pressure, lipid levels, and obesity. At the population level, a small reduction of a risk factor, e.g., systolic blood pressure or LDL cholesterol, while having little impact on the individual could substantially reduce the burden of CVD at the country level. Primordial prevention has been described as one of the “best buys” in health promotion [21]. Primordial prevention largely requires action at the policy and political level through legislation and education through media.

An example of success in this strategy is the Polish experience [22] of using taxes and subsidies to reduce the consumption of butter, increase use of vegetable oils, and increase intake of fruits and vegetables with significant decrease in CVD mortality. Finland was one of the first countries to demonstrate the benefit of such prevention strategies [23].

Primordial prevention alone will not suffice, as it does not address individuals at high risk of disease who will need more intensive preventive measures. The current strategy for primary prevention involves identifying persons without CVD but at risk of getting it and treating them with both lifestyle modification and pharmacotherapy to reduce their risk factor levels to preset targets. Such a process involves screening asymptomatic individuals for level of risk (high risk, ≥20 % risk of event over 10 years; moderate risk, 10–19 % risk over 10 years; and low risk, ≤10 % risk over 10 years). This would involve measuring anthropometry (BMI and/or waist circumference), blood pressure, and usually lipids (although non-laboratory-based risk scoring systems are also available). National policies and guidelines should be available to recommend at which level of risk, intervention with lifestyle modification, and pharmacotherapy is to follow. Such levels may vary from country to country. Therapies are targeted to lower blood pressure and lipids and, possibly, inhibit platelet function with use of multiple medications. Subsequent follow-up of the subjects is required with repeat measurements of risk factors and adjustment of medication to achieve the required target risk factor levels. Such a strategy is not practical on a large scale, which is required to address the epidemic proportions of the problem. In addition, this strategy fails to take into account the continuous nature of risk factors by setting specific levels of risk factors at which to intervene.

Secondary prevention on the other hand requires less effort and cost to identify people requiring intervention since such people have already had a symptomatic coronary artery disease (CAD) or stroke event. They can be identified at the time of the index event or at subsequent follow-up visits. Such people are also likely to be more motivated both for follow-up and to adhere to pharmacotherapy and lifestyle modification. Yet even here, such adherence is less than desirable. The PURE (Prospective Urban Rural Epidemiology) study showed that in the community among 5,650 subjects with prior self-reported CAD events and 2,292 with stroke, overall only 25 % were taking antiplatelet medication, 17 % beta-blockers, 20 % ACEI/ARBs, and 15 % statins. Even in high-income countries, the percentages of those on medication were unsatisfactory (62, 40, 50, and 67 %, respectively), while it was abysmal in low-income countries (9, 10, 5, and 3 %, respectively) [24]. Further, the EUROSPIRE III survey found that among patients in high-income countries in Europe after a CAD event, 17 % still smoked tobacco, 35 % were obese, 56 % had suboptimal blood pressure control, and 25 % had elevated cholesterol [25].

In 2002, the WHO advised strategies designed for control of CVD at the population level. These called for:

While lifestyle interventions are certainly of great importance and need to be maximally encouraged (Chap.​ 30) by governmental policies and media campaigns, they have generally not had a major sustained impact in reducing CVD events [26]. In people at moderate or greater risk and in those who have had a CVD event, pharmacotherapy is required. In situations where a large number of people need to be treated, the need for multiple tablets and the current requirement for screening and treating risk factors to preset targets may not succeed. It is in such a scenario that we have to consider the polypill concept.

Broadly, the polypill concept is that in view of the fact that a unit of reduction in a risk factor will result in a constant proportional reduction in risk of events independent of the initial value of the risk factor, reducing a range of risk factors using a combination pill in all subjects with moderate or greater risk will reduce cardiovascular events significantly and be cost-effective. This hypothesis was proposed by Wald and Law in their seminal paper in 2003 [18]. They proposed a single pill containing medications to reduce BP, lipids, and homocysteine as well as platelet aggregation. They further proposed that in view of the fact that age is the strongest risk factor, instead of screening the population for risk factors to identify those at “moderate” risk, such a pill could be given to all people who have had a cardiovascular event (secondary prevention) as well as to all people over the age of 55 years (primary prevention) since this age itself will put them at moderate risk. As will be discussed below, using a series of meta-analyses, they hypothesized that such a strategy could lower CVD events significantly – CAD events by 88 % and strokes by 80 %. About one in three people would directly benefit each on average gaining 11–12 years of life free of heart attack or stroke. In those aged 55–64 years, this increase of disease-free life could be as much as 20 years. The antihypertensive composition of the pill proposed by them consisted of half doses of three drugs to reduce side effects. They also proposed the use of out-of-patent medications to reduce cost. The polypill concept is just that a hypothesis that including in a single pill different component to address multiple risk factors would be effective. If proven, the polypill hypothesis could bridge the gap between evidence and practice by improving access and adherence to medication with the possibility of large benefits at low cost.