A Pilot Double-Blind Randomised Placebo-Controlled Trial of the Effects of Fixed-Dose Combination Therapy ('Polypill') on Cardiovascular Risk Factors

Int J Clin Pract. 2010 Aug;64(9):1220-7. doi: 10.1111/j.1742-1241.2010.02412.x.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / pharmacology*
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology*
  • Aspirin / administration & dosage
  • Aspirin / pharmacology
  • Atorvastatin
  • Blood Pressure / drug effects*
  • Cardiovascular Diseases / etiology
  • Cholesterol, LDL / drug effects*
  • Chronic Disease
  • Double-Blind Method
  • Drug Combinations
  • Enalapril / administration & dosage
  • Enalapril / pharmacology
  • Female
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / pharmacology
  • Humans
  • Hydrochlorothiazide / administration & dosage
  • Hydrochlorothiazide / pharmacology
  • Male
  • Middle Aged
  • Pilot Projects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology*
  • Pyrroles / administration & dosage
  • Pyrroles / pharmacology
  • Risk Factors
  • Tablets

Substances

  • Anticholesteremic Agents
  • Antihypertensive Agents
  • Cholesterol, LDL
  • Drug Combinations
  • Heptanoic Acids
  • Platelet Aggregation Inhibitors
  • Pyrroles
  • Tablets
  • Hydrochlorothiazide
  • Enalapril
  • Atorvastatin
  • Aspirin

Associated data

  • ISRCTN/ISRCTN43076122