Is there a magic pill for the world’s leading cause of death? Some experts believe a combination medicine, or “polypill,” can offer dynamic protection against heart disease. However, critics are wary about broadly dispensing treatment without individualized care and monitoring. Could a polypill erase disparities in underserved populations, or does it just put a Band-Aid on a larger problem? Here’s how the research stacks up.
What Is a Polypill?
A polypill contains 3 to 4 low-dose pharmaceuticals designed to decrease multiple cardiovascular risk factors at once.1 Cardiovascular polypills usually contain at least 1 antihypertensive and 1 statin, and may or may not have other additions like aspirin and folic acid. Researchers introduced the polypill concept in 2003, advocating for the proactive treatment of everyone older than 54 years, regardless of their lipid levels or blood pressure.Using data from clinical trials and meta-analyses, early polypill researchers predicted an 88% reduction in ischemic heart disease and an 80% decrease in occurrence of stroke with mass administration.1
Today, proponents of polypill therapy say it improves adherence through the simplicity of a single daily pill. Other advantages of this fixed low dose include an optimal safety profile and a decreased need for follow-up visits for dose adjustments.2 As an effective preventative tool against stroke, polypill therapy also has the potential for significant cost savings, both in health care dollars and quality years of life. However, the jury is still out on how polypill therapy will affect large populations in the absence of supervised care.
Is Polypill Therapy Effective?
Large-scale trials of cardiovascular polypills have not entirely lived up to their originator’s predictions. Nonetheless, polypills have demonstrated significant benefits in stroke prevention. For example, in the 2016 HOPE-3 trial, a polypill containing candesartan, hydrochlorothiazide, and rosuvastatin produced a 44% decrease in stroke risk compared with placebo.1 Another study, known as the Polylran study in 2019, found that a polypill had a 56% reduction in nonfatal strokes and a 62% reduction in fatal strokes.1 Finally, the 2021 TIPS study demonstrated that an aspirin-containing polypill led to similar effects, lowering stroke occurrence by 58% compared with placebo.1
In 2019, the New England Journal of Medicine published a randomized, controlled trial on 303 low-income adults from Alabama receiving care through a federally-qualified community health center.2 Participants had an average annual income below $15,000 and were randomly assigned to receive standard care or a polypill. Each polypill contained 10 mg atorvastatin, 2.5 mg amlodipine, 25 mg losartan, and 12.5 mg hydrochlorothiazide and cost $26 per month. After 1 year of treatment, those taking the polypill had an average systolic blood pressure reduction of 9 mm Hg, compared to just 2 mm Hg in the standard care group. The polypill group also experienced an average 15 mg/dL low-density lipoprotein cholesterol (LDL-C) level decrease versus 4 mg/dL for the standard care group.
The researchers concluded, “A polypill-based strategy led to greater reductions in systolic blood pressure and LDL cholesterol level than were observed with usual care in a socioeconomically vulnerable minority population.”2
The New England Journal of Medicine later published a phase 3 randomized controlled trial of older adults with a recent history of myocardial infarction in 2022.3 The researchers randomly assigned 2499 participants to receive either polypill treatment or standard care for a median of 36 months. This polypill contained aspirin, ramipril, and atorvastatin. Participants in the polypill group had a lower frequency of cardiovascular events than those receiving standard care during the study period. The researchers attributed some of this benefit to better compliance with polypill therapy. Overall, patients with high adherence to their prescribed medications experienced a 27% lower cardiovascular risk.
Overcoming Barriers With Polypill Therapy
Public health officials have identified glaring disparities among underserved populations. Various socioeconomic factors lead to marked outcome differences, including a 2-fold higher incidence of fatal cardiovascular heart disease events in non-Hispanic Black men versus non-Hispanic White men between the ages of 45 to 64 years and a 1.44-fold higher risk for Black women versus White women of the same age group.4
The American Heart Association has identified 7 core health behaviors and factors that define heart health. These include smoking, physical activity, diet, body mass index, cholesterol levels, blood pressure, and glucose control. Perhaps one of the biggest contributors to higher stroke risk is poor diet quality, with observational studies noting a dose-response relationship between healthy eating and cardiovascular death and disability.4
Diet quality directly correlates with socioeconomic status, race, ethnicity, education level, and the use of food assistance programs. Racially-segregated neighborhoods, food insecurity, and food deserts remain despite the efforts of government food assistance programs. A polypill may help decrease some stroke risk, but it doesn’t address these critical issues.
The obvious benefits of polypill therapy include measurable outcome differences in stroke risk and better adherence to proven preventative medications. However, nutrition, smoking, and physical activity still warrant attention as their impacts are far-reaching beyond cardiovascular health, extending to general well-being and other disease prevention. As more research on polypill therapy continues to unfold, it may very well earn a place in the primary prevention of strokes, especially when combined with risk modification programs and the continued promotion of healthier living.5
Where Do We Go From Here?
Polypill therapy promises a simple solution for a serious problem. In underserved communities plagued with heart-related death and disability, polypill therapy shows clear potential to make a lasting impact. However, any benefits from polypill therapy must not overshadow the continued need for individualized healthcare and comprehensive lifestyle programs. Pairing thoughtful administration of polypill therapy with community and personalized risk reduction can build a bridge between the best of both worlds.
This article originally appeared on The Cardiology Advisor
- Sarfo FS, Nichols M, Opare-Addo PA, Ovbiagele B. Polypill programs to prevent stroke and cut costs in low income countries: moving from clinical efficacy to pragmatic implementation. Stroke. Published online January 23, 2023. doi:10.1161/STROKEAHA.122.039567
- Muñoz D, Uzoije P, Reynolds C, et al. Polypill for cardiovascular disease prevention in an underserved population. N Engl J Med. Published online September 19, 2019. doi:10.1056/NEJMoa1815359
- Castellano JM, Pocock SJ, Bhatt DL, et al. Polypill strategy in secondary cardiovascular prevention. N Engl J Med. Published online September 15, 2022. doi:10.1056/NEJMoa2208275
- Kris‐Etherton PM, Petersen KS, Velarde G, et al. Barriers, opportunities, and challenges in addressing disparities in diet‐related cardiovascular disease in the United States. JAHA. Published online March 23, 2020. doi:10.1161/JAHA.119.014433
- Brainin M, Teuschl Y, Martins S. Polypill: benefits seen for stroke and other outcomes. Stroke. Published online June 21, 2022. doi:10.1161/STROKEAHA.122.037313