Although fixed-dose combination (or polypill) therapy has been proposed as a cost-saving approach to improve drug adherence and reduce the risk of cardiovascular disease (CVD), the long-term effectiveness of such a strategy has not yet been established, particularly in primary prevention settings. Investigators in the PolyIran study now report that a fixed-dose polypill strategy reduces the risk of cardiovascular events compared with non-pharmacological interventions.

The PolyIran study was a two-group, pragmatic study nested within the Golestan Cohort Study, a large cohort study with 50,045 participants from the Golestan region of Iran. In PolyIran, 3,421 individuals received a four-component polypill containing aspirin, atorvastatin, hydrochlorothiazide and either enalapril or valsartan, in addition to non-pharmacological intervention, which involved educational training about healthy lifestyle habits (polypill group), whereas 3,417 individuals received non-pharmacological intervention only (minimal-care group).

At the 5-year follow-up, 5.9% of individuals in the polypill group had major cardiovascular events compared with 8.8% of the minimal-care group (adjusted HR 0.66, 95% CI 0.55–0.80). This benefit was independent of whether the individual had pre-existing CVD. The reduction in risk of CVD was even more pronounced when comparing only those participants in the polypill group who had high adherence to the polypill with those in the minimal-care group (adjusted HR 0.43, 95% CI 0.33–0.55). Importantly, the rate of adverse events, such as intracranial haemorrhage, was not significantly different between the two treatment groups. Furthermore, in a post-hoc analysis, longer duration of polypill use was linked with a stronger protective effect.

“This pragmatic trial provides evidence that a polypill strategy could be considered as part of preventive programmes to reduce [CVD] burden among eligible adults, especially in [low-income and middle-income countries],” conclude the investigators.