Objectives The aim of the present study was to estimate the cost-effectiveness 
of the polypill in the primary prevention of cardiovascular disease. Design A 
health economic modelling study. Setting Primary healthcare in the Netherlands. 
Participants Simulated individuals from the general Dutch population, aged 45-75 
years. Interventions Opportunistic screening followed by prescription of the 
polypill to eligible individuals. Eligibility was defined as having a minimum 
10-year risk of cardiovascular death as assessed with the Systematic Coronary 
Risk Evaluation function of alternatively 5%, 7.5% or 10%. Different versions of 
the polypill were considered, depending on composition: (1) the Indian polycap, 
with three different types of blood pressure-lowering drugs, a statin and 
aspirin; (2) as (1) but without aspirin and (3) as (2) but with a double statin 
dose. In addition, a scenario of (targeted) separate antihypertensive and/or 
statin medication was simulated. Primary outcome measures Cases of acute 
myocardial infarction or stroke prevented, quality-adjusted life years (QALYs) 
gained and the costs per QALY gained. All interventions were compared with usual 
care. Results All scenarios were cost-effective with an incremental 
cost-effectiveness ratio between €7900 and 12 300 per QALY compared with usual 
care. Most health gains were achieved with the polypill without aspirin and 
containing a double dose of statins. With a 10-year risk of 7.5% as the 
threshold, this pill would prevent approximately 3.5% of all cardiovascular 
events. Conclusions Opportunistic screening based on global cardiovascular risk 
assessment followed by polypill prescription to those with increased risk offers 
a cost-effective strategy. Most health gain is achieved by the polypill without 
aspirin and a double statin dose.