The current study suggests that cardiovascular risk reduction medications are under-utilized among US adults. Even among the 15.4 million US adults with a history of CVD, fewer than 60% are taking aspirin and beta-blockers. We project that the population-wide use of polypills containing aspirin, a thiazide-type diuretic, an ACE-inhibitor and a statin among all US adults ≥ 55 years of age has the potential to prevent millions of CHD and stroke events over the next 10 years. The potential for substantial risk reduction was also present when polypills were considered only for US adults with a history of CVD.
Results from a recent randomized controlled trial indicated a polypill containing aspirin, simvastatin, atenolol, ramipril and a thiazide diuretic improved individuals' cardiovascular risk profile(24
). In this trial, the polypill provided a similar degree of lowering blood pressure and heart rate lowering effects when compared to its individuals antihypertensive components. Additionally, the polypill resulted in a significant lowering of LDL-cholesterol and urinary 11-dehydrothromboxane B2, compared to placebo. However, the effect in those randomized to the polypill was less than their counterparts randomized to simvastatin (27 versus 32 mg/dL) and aspirin (283.1 versus 350.0 ng/mmol creatinine). Thus, the authors concluded that the polypill being tested may not provide the benefits expected based on the multiplicative effects of its individual components. Despite this caveat, based on the reductions experienced for individuals randomized to receive this polypill (7.4 mmHg reduction in systolic blood pressure, 27 mg/dL reduction in LDL-cholesterol and 283.1 reduction in ng/mmol creatinine 11-dehydrothromboxane B2), a substantial reduction in CVD risk could be expected. In fact, in a sensitivity analysis assuming 20% lesser reductions in events than expected from use of individual polypill medications, we project that millions of CHD and stroke events may still be prevented over a 10 year period.
Prior epidemiological analyses have investigated the potential benefits of polypills. For example, a study by Gaziano and colleagues reported a multi-drug primary prevention strategy of treating patients from low and middle income countries with a 10-year absolute risk of cardiovascular disease of more than 5% may result in reductions of 42% to 57% in lifetime risk of death from cardiovascular disease(26
). Additionally, a report “Assessing Cost-Effectiveness in Prevention” from Australia detailed a potential for 230,000 disability-adjusted life years gained through population-wide polypill use(27
). The polypill was also found to result in cost-savings.
While the projected potential benefits of polypills as estimated in the current study are compelling, Lonn and colleagues recently described several reservations regarding the polypill that need to be addressed prior to fully advocating their broad adoption (11
). Importantly, data are still needed from randomized controlled trials on the benefits of polypills in preventing CHD and strokes. Additional items cited include determining the ideal pharmaceutical formulation of polypills, polypill adherence issues, the abandonment of healthy lifestyles by patients taking polypills, and the acceptability of taking additional medications by the population at large. Caution is warranted until data become available to address these uncertainties.
The expected benefits of wide-spread polypill use must be balanced by the projected occurrence of new adverse side effects in up to 17% of its users. However, these will not tend to be severe (e.g., cough, dizziness, nausea, and abdominal discomfort). While more severe side effects (e.g., bleeding, angioedema) do occur with the use of the polypill drugs, these are unlikely to occur frequently. However, such side effects may also limit the beneficial effects of polypill use.
Cardio-protective medications are under-utilized among US adults. The reasons why patients do not take these medications are varied and include their beliefs about pharmacologic medications, side effects, and lack of access to healthcare(28
). Incorporating aspirin, antihypertensive medications and statins into a single pill is widely predicted to improve medication use and adherence(29
). Several studies suggest that complex medication taking regimens are an important barrier to achieving high medication adherence among patients with hypertension and high cholesterol. The use of polypills has the potential to make medication-taking regimens simpler, likely resulting in improved medication adherence and possibly reduced CVD incidence.
The current study has potential limitations. For example, we relied on projections to estimate the CHD and stroke risk reduction associated with polypill use. Additionally, while risk reduction benefits and side effects are based on published data from randomized trials, 10 years of follow-up for the benefits and side effects were not available. Data are not currently available on the risk reduction benefits of polypills and, thus, the potential benefits relied on previously published meta-analyses. NHANES 2007-2008 provides nationally representative estimates for the civilian non-institutionalized US population but it does not have data on CHD and stroke incidence. Therefore, we used data from three large cohort studies. Although these cohorts are population-based and maintain active follow-up and adjudication of incident fatal and non-fatal CVD events, they are not based upon nationally representative samples.
Several polypills aimed at CVD reduction are currently under development and being evaluated in randomized controlled trials. While the CVD risk reduction benefits of polypills still need to be determined in randomized controlled trials, the use of polypills among US adults at high risk for CVD has the potential to prevent millions of CHD and stroke events.