A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy (‘polypill’) on cardiovascular risk factors


  • Clinical Trial Registration Number: ISRCTN43076122.

  • Disclosures
    All authors declare that they have no conflicts of interest in relation to this study.

Tom Marshall,
Public Health, Epidemiology & Biostatistics,
University of Birmingham, Birmingham, UK
Tel.: 0121 414 7832
Fax: 0121 414 7878
Email: T.P.Marshall@bham.ac.uk


Aim:  Our objective was to investigate the effects and tolerability of fixed-dose combination therapy on blood pressure and LDL in adults without elevated blood pressure or lipid levels.

Methods:  This was a double-blind randomised placebo-controlled trial in residents of Kalaleh, Golestan, Iran. Following an 8-week placebo run-in period, 475 participants, aged 50 to 79 years, without cardiovascular disease, hypertension or hyperlipidaemia were randomised to fixed-dose combination therapy with aspirin 81 mg, enalapril 2.5 mg, atorvastatin 20 mg and hydrochlorothiazide 12.5 mg (polypill) or placebo for a period of 12 months. The primary outcomes were changes in LDL-cholesterol, systolic and diastolic blood pressure and adverse reactions. Analysis was by intention-to-treat basis.

Results:  At baseline, there were differences in systolic blood pressure (6 mmHg). Taking account of baseline differences, at 12 months, polypill was associated with statistically significant reductions in blood pressure (4.5/1.6 mmHg) and LDL-cholesterol (0.46 mmol/l). The study drug was well tolerated, but resulted in the modest reductions in blood pressure and lipid levels.

Conclusion:  The effects of the polypill on blood pressure and lipid levels were less than anticipated, raising questions about the reliability of the reported compliance. There is a case for a fully powered trial of a polypill for the prevention of cardiovascular disease.