US Life Expectancy and Cardiovascular Disease Prevention: Is It Time for a Cardiovascular Disease Prevention Polypill?

Life expectancy in the United States has increased by 2 years per decade for most of the twentieth century.^1-2 A truly remarkable achievement!  The most important improvement during this time was a decrease in cardiovascular disease mortality.  The decline in cardiovascular mortality was attributed by improved diagnostics, treatments, and healthier lifestyles.²   However, more recently life expectancy has leveled and started to decline.³ Why? 

Drug-related deaths are a potential cause, but the improvement trajectory was due to cardiovascular causes.³ United States data from the Centers of Disease Control Wonder Database shows that cardiovascular disease deaths have flattened the life expectancy curve at age 25 years old by 1.14 years in women and men between 2010 and 2017.  Rising drug-related deaths were only 0.1 years in women and 0.4 years in men. 

So what do we do now? We maybe at a crossroad of cardiovascular prevention.  Two strategies that have been proposed and studied.  The first is precision medicine.  It advocates for a rigorous study of individual characteristics to predict drug, dose, and potentially schedule.  This method will require substantially more time and resources to become a reality, if it is even possible.  The second is administration of multiple cardiovascular prevention medications with proven efficacy and low-adverse event rate in one pill-called the polypill.  A concept that has been around for 20 years.⁴ Multiple polypill formulations have been studied.^5-7 They all contain a low-dose off-patent statin, at least one class of antihypertensive agent, and some with low-dose aspirin. Administered daily, the goal is to reduce LDL-C and blood pressure in middle-aged to older adults at risk for cardiovascular disease.  Benefits of this approach is wider coverage, adherence advantages, and lower cost.

Study results have shown mixed results.  A 2017 Cochrane systematic review and meta-analysis of 13 trials enrolling 9059 participants, found no difference in ASCVD events and all-cause mortality.⁵ Improvements in LDL-C and blood pressure were demonstrated in patients who had indications for treatment. Adverse events were higher among patients randomized to the polypill.  Two recently published studies have provided additional data. The first from Iran of 6838 participants over 5 years, found no difference in all-cause mortality or adverse events between the polypill and augmented (referred for blood pressure control) usual care.⁶   The second study conducted in federally qualified health centers in the United States, found a similar direction in LDL-C and blood pressure reduction and no differences in adverse event rates.^{7 There} are ongoing studies.⁴

At present, a cardiovascular prevention polypill for widespread use cannot be justified based on available evidence.  Larger, randomized, usual-care comparison trials are needed in developing and developed countries to justify this therapy in the future.

Mark A. Munger, PharmD, FCCP, FACC, is a professor of pharmacotherapy and adjunct professor of internal medicine, at the University of Utah, where he also serves as the associate dean of Academic Affairs for the College of Pharmacy. 

References:

1. National Center for Health Statistics. Health, United States, 2018 with Chartbook on Trends in the Health of Americans.  https://www.cdc.gov/nchs/data/hus/hus18.pdf? Accessed 08/2020
2. Jemal A, Ward E, Hao Y, Thun M. Trends in the leading causes of death in the United States. 1970-2002. JAMA 2005;194:1255-9.
3. Mehta NK, Abrams LR, Myrskyla M.  Us life expectancy stalls due to cardiovascular disease not drug deaths.  PNAS www.pnas.org/cgi/doi/10.1073/pnas.1920391117  
4. Huffman MD, Salem A, Patel A. Implementation strategies for cardiovascular polypills. JAMA 2019;322(23):2279-80.
5. Bahiru E, de Cates AN, Farr MR, et al. Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease. Cochrane Database Syst Rev 2017;3:CD009868.
6. Roshandel G, Khoshnia M, Poutschi H, et al. Effectiveness of polypill for primary and secondary prevention of cardiovascular disease (PolyIran). Lancet 2019;394(10199):672-83.
7. Muňoz D, Uzoije P, Renolds C, et al. Polypill for cardiovascular disease prevention in a underserved population. N Engl J Med 2019;381(12):1114-23.