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


CONCLUSIONS
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.
Malekzadeh
F
F
Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Marshall
T
T
Pourshams
A
A
Gharravi
M
M
Aslani
A
A
Nateghi
A
A
Rastegarpanah
M
M
Khoshnia
M
M
Semnani
S
S
Salahi
R
R
Thomas
G N
GN
Larijani
B
B
Cheng
K K
KK
Malekzadeh
R
R
D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000209:etiology; D008078:Cholesterol, LDL / Q000187:drug effects*; D002908:Chronic Disease; D004311:Double-Blind Method; D004338:Drug Combinations; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D012307:Risk Factors; D013607:Tablets
D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D008078:Cholesterol, LDL; D004338:Drug Combinations; D006538:Heptanoic Acids; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D013607:Tablets; D006852:Hydrochlorothiazide; D004656:Enalapril; D000069059:Atorvastatin; D001241:Aspirin