By Lilian Anekwe
A randomised controlled trial of a polypill for the primary prevention of cardiovascular disease has found that the effects of the drug on blood pressure and lipids were ‘less than anticipated'.
A debate has raged for several years around whether a combination polypill – including antiplatelet agents, blood pressure-lowering and lipid-lowering drugs – could reduce the incidence of cardiovascular disease, or prevent the onset of cardiovascular disease in at-risk patients.
A team of researchers from the UK and Iran randomised 475 patients aged 50 to 79 without cardiovascular disease, hypertension or hyperlipidaemia, following an eight-week placebo run-in period, to either a fixed-dose combination therapy with aspirin 81mg, enalapril 2.5mg, atorvastatin 20mg and hydrochlorothiazide 12.5mg or placebo for 12 months.
Despite baseline differences in systolic blood pressure of 6 mmHg, patients on the polypill showed a 4.5 mmHg systolic and 1.6 mmHg diastolic reduction in blood pressure and a 0.46 mmol ? l or 16% reduction in LDL-cholesterol – the equivalent of a 34% reduction in CHD risk and a 21% reduction in stroke.
But the researchers described the reduction as ‘statistically significant, but unexpectedly modest reductions'.
This is because a half standard dose of thiazide and quarter standard dose of ACE inhibitor would be expected to lower blood pressure by 6.5m mmHg systolic and 2.0 mmHg diastolic, in this population with a mean blood pressure of 125 /78 mmHg.
But the observed effect was only three quarters of the expected reduction.
Similarly atorvastatin 20 mg would be expected to reduce LDL-cholesterol by 43%, so the observed 16% reduction was about one-third of that predicted.
Overall, compliance was estimated at between 65-70%. This level of compliance suggests that the drug may have been less efficacious than predicted.
Researcher Dr Tom Marshall, senior lecturer in public health and epidemiology at the University of Birmingham concluded in the Interrnational Journal of Clinical Practice: ‘The effects of the polypill on blood pressure and lipid levels were less than anticipated, raising questions about the reliability of the reported compliance.'
‘Indications from this pilot study are that a four component polypill has the potential to reduce the incidence of CVD by about one third. This effect size may be sufficient to be cost-effective.'
In an accompanying editorial, Dr Rubin Minhas, a GP and clinical director of the BMJ evidence centre, wrote: ‘These studies show that a formulation of 4–5 drugs for cardiovascular prevention is possible and seems to be safe in long-term therapy. However, all these therapies require long-term adherence to have the desired effects so this implies their greater utility in secondary prevention.'
International Journal of Clinical Practice, published online 13 July 2010Patients on the polypill showed modest reductions in BP and lipids