A Pilot Double-blind Randomised Placebo-controlled Trial of the Effects of Fixed-dose Combination Therapy (‘polypill’) on Cardiovascular Risk Factors

Aim: Our objective was to investigate the effects and tolerability of _xed-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 undertaken in residents of Kalaleh, Golestan, Iran. Following an eight week placebo run-in period, 475 participants, aged 50 to 79 years, who had no cardiovascular disease, hypertension or hyperlipidemia were randomised to _xeddose 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 into account the baseline differences, at 12 months, the polypill was associated with statistically signi_cant 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 reported compliance. There is a case for a fully powered trial of the polypill for prevention of cardiovascular disease.