Polypill Therapy Cost-Effective for CVD Risk in Underserved Populations

A cardiovascular polypill, comprised of a statin and multiple half-standard dose anti-hypertensives, could be a high-value intervention, and reduce health disparities among a low-income, majority-Black population, according to a new economic evaluation.1

Data from the Southern Community Cohort Study (SCCS) Polypill Trial reported the value of a polypill in addressing cardiovascular disease (CVD) risk factors among those with limited access to preventive healthcare.2 This evaluation on a computer simulation model revealed the high value of the polypill if priced at ≤$463 yearly.1

“The polypill would be highly cost-effective among individuals eligible for the SCCS Polypill Trial identified opportunistically,” wrote the investigative team, led by Ciaran N. Kohli-Lynch, PhD, department of preventive medicine, Feinberg School of Medicine, Northwestern University. “However, it may be challenging for health systems to reach underserved populations.”

Race and ethnicity, as well as income level, are notable patient factors impacting CVD rates across the US.3 CVD risk elevations are observed in both non-Hispanic Black and lower-income cohorts, compared with non-Hispanic White and higher-income peers. These disparities are attributed to reasons such as clinical inertia, little access to healthcare, and issues with medication adherence.

Cardiovascular polypills potentially dissolve these barriers and benefit patient adherence more effectively than traditional treatment using multiple pills. The SCCS Polypill trial involved half doses of 4 preventive agents: atorvastatin 10 mg, amlodipine 2.5 mg, losartan 25 mg, and hydrochlorothiazide 12.5 mg.2

After 12 months, those treated with a polypill reported a mean reduction of 7 mmHg in systolic blood pressure (SBP) and 11 mg/dL in LDL-C level, compared with the control arm. For this trial analysis, a discrete-event simulation version of the CVD policy model replicated clinical and economic outcomes from a healthcare perspective, with a time horizon of 10 years.1

Polypill treatment was granted an annual cost of $463 in the base case analysis. Two cohorts were analyzed, including an SCCS Polypill trial cohort of 100,000 participants and all trial-eligible non-Hispanic Black adults in the US. The analysis’ primary outcome was direct health care costs and quality-adjusted life-years (QALYs), discounted 3% annually, and the incremental cost per gain in QALYs.

Projections centered on the trial-representative cohort found polypill treatment could yield an estimated 1190 additional QALYs versus usual care, with a cost of approximately $10,152,000. Overall, at the base-case price, Kohli-Lynch and colleagues estimated polypill treatment at $8560 per QALY gained compared with usual care. It was estimated at high value (<$50,000 per QALY) in nearly all (99%) simulations.

Estimates suggested polypill treatment was high-value priced at ≤$559 per year and cost-saving at ≤$443 per year. Most sensitivity analyses confirmed polypill treatment remained high-value. From a secondary analysis of 3,602,427 trial-eligible non-Hispanic Black US adults, Kohli-Lynch and colleagues estimated polypill treatment remained high-value, with estimates at $13,400 per gained QALY.

“Our results may be particularly relevant to other patient groups with low rates of treatment persistence and adherence, including community-dwelling older adult patients with chronic polypharmacy and younger adults with elevated cardiovascular risk factors,” Kohli-Lynch and colleagues added.

An accompanying editorial by Clyde W. Yancy, MD, MSc, division of cardiology, Northwestern University, cited a 2014 recommendation by the US Food and Drug Administration (FDA) concluding that, although outcomes trials are unnecessary for polypill approval, a fixed-dose product requires ≥1 new molecular entity.4

Irrespective of the low-risk profile of half-dose therapy, concerns surround the need for titration, adverse effects, and overtreatment of the polypill. However, Yancy indicated that this regulatory question and issues in implementation are not insurmountable, suggesting the results of the SCCS cohort are game-changing for the polypill.

“The cohort in SCCS definitively recalibrates the argument,” Yancy wrote. “There is no social determinant of health more compelling than poverty, and in many US communities, poverty is pervasive, and CVD is epidemic. The resultant but unmeasurable societal costs are incalculable. A disruptive solution is needed.”

References

1. Kohli-Lynch CN, Moran AE, Kazi DS, et al. Cost-Effectiveness of a Polypill for Cardiovascular Disease Prevention in an Underserved Population. JAMA Cardiol. Published online January 08, 2025. doi:10.1001/jamacardio.2024.4812
2. Muñoz D, Uzoije P, Reynolds C, et al. Polypill for Cardiovascular Disease Prevention in an Underserved Population. N Engl J Med. 2019;381(12):1114-1123. doi:10.1056/NEJMoa1815359
3. Jacobs JA, Addo DK, Zheutlin AR, et al. Prevalence of Statin Use for Primary Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and 10-Year Disease Risk in the US: National Health and Nutrition Examination Surveys, 2013 to March 2020 [published correction appears in JAMA Cardiol. 2023 Jul 1;8(7):710. doi: 10.1001/jamacardio.2023.1358]. JAMA Cardiol. 2023;8(5):443-452. doi:10.1001/jamacardio.2023.0228
4. Yancy CW, Fonarow GC. Genius and the CVD Polypill—A Step Toward Achieving Health Equity? JAMA Cardiol. Published online January 08, 2025. doi:10.1001/jamacardio.2024.4820