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

Fatemeh Malekzadeh (1) , Tom Marshall (2) , Akram Pourshams (1) , Mina Gharravi (1) , Afshin Aslani (1) , Alireza Nateghi (1) , Mansoor Rastegarpanah (1) , Masoud Khoshnia (1) , Shahryar Semnani (3) , Rasool Salahi (3) , Neil Thomas (4) , Bagher Larijani (1) , Kk Cheng (4) , Reza Malekzadeh (1)

1 Tehran University of Medical Sciences
2 Public Health, Epidemiology and Biostatistics
3 Golestan University of Medical Sciences
4 University of Birmingham [Birmingham]

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 eight 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. Results: At baseline there were differences in systolic blood pressure (6 mm Hg). Taking account of baseline differences, at 12 months polypill was associated with statistically significant reductions in blood pressure (4.5/1.6 mm Hg) and LDL-cholesterol (0.46 mmol/L). The study drug was well tolerated but resulted in 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 reported compliance. There is a case for a fully powered trial of a polypill for prevention of cardiovascular disease.

Mots clés: Medicine

Fatemeh Malekzadeh, Tom Marshall, Akram Pourshams, Mina Gharravi, Afshin Aslani, et al.. A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy (“polypill”) on cardiovascular risk factors. International Journal of Clinical Practice, 2010, 64 (9), pp.1220. ⟨10.1111/j.1742-1241.2010.02412.x⟩. ⟨hal-00555329⟩