Polypill Therapy, Subclinical Atherosclerosis, and Cardiovascular Events – Implications for the Use of Preventive Pharmacotherapy: Multi-Ethnic Study of Atherosclerosis (MESA)

Study Questions:

Can the coronary artery calcium score (CAC) be used to define the target population to treat with a polypill?


Participants from MESA (the Multi-Ethnic Study of Atherosclerosis) were stratified using the criteria of four polypill studies (TIPS, Poly-Iran, Wald’s, and the PILL collaboration). The authors compared coronary heart disease (CHD) and cardiovascular disease (CVD) event rates, and calculated 5-year number needed to treat (NNT) after stratification based on the CAC score.


Among MESA participants eligible for the TIPS, Poly-Iran, Wald’s, and PILL collaboration, a CAC = 0 was observed in 58.6%, 54.5%, 38.9% and 40.8%, respectively. While the rate of CHD events among those with CAC = 0 varied from 1.2-1.9 events per 1,000 patient-years, those with CAC 1-100 had event rates ranging from 4.1-5.5, and in those with CAC >100, the event rate ranged from 11.7-13.3. The estimated 5-year NNT to prevent one CVD event ranged from 84-134 for patients with CAC = 0, 40-55 for those with CAC 1-100, and 19-21 for those with CAC >100.


Among individuals eligible for treatment with the polypill, the majority of events occurred in those with CAC >100. The group with CAC = 0 had a very low event rate and a high projected NNT. The avoidance of treatment in individuals with CAC = 0 could allow for significant reductions in the population considered for treatment.


The CAC score is very appealing compared to risk factor estimated event rates because it provides direct evidence for preclinical atherosclerosis and has been validated to define high risk. However, considering the objective is to extend life free of CV events, there are not adequate data to support withholding a theoretical polypill in persons at low or intermediate risk with a low or zero CAC score.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Atherosclerotic Disease (CAD/PAD)

Keywords: Metabolic Syndrome X, Iran, Ethnic Groups, Coronary Artery Disease, Dyslipidemias, Atherosclerosis, Calcinosis, Risk Factors, Coronary Vessels

< Back to Listings