Most national newspapers have reported on a study of a ‘polypill’ that can “halve” the risk of heart disease and stroke. The Daily Telegraph said the new “five-in-one pill can significantly reduce the risk of heart disease and stroke in even healthy patients, and could save tens of thousands of lives a year”. The Independent says that the pill “costs pennies”.
The study was carried out in India as a twelve-week trial in 2,053 people (aged 45 to 80 years old) who had no known cardiovascular disease, but had at least one risk factor, such as diabetes or smoking. Some of the participants were given one “Polycap” daily, while others took different combinations of the polypill’s constituent drugs (including cholesterol-lowering drugs, aspirin, and blood pressure drugs).
The trial was well-conducted, and its findings are promising. It indicates that the formulation of this particular polypill is at least as effective as the drugs given separately (other than its effect on lipids). Whether or not it actually reduces mortality from strokes and heart disease will need to be demonstrated by larger trials.
Where did the story come from?
The trial was conducted by doctors from The Indian Polycap Study (TIPS) and funded by the makers of the Polycap, Cadila Pharmaceuticals. The study was published in the peer-reviewed medical journal The Lancet.
What kind of scientific study was this?
This was a phase II randomised controlled trial of the Polycap, a new capsule pill that combines several existing drugs that are known to reduce the risk of coronary heart disease and stroke by improving lipid profiles, blood pressure and clotting factors in the blood.
The Polycap contains
- thiazide (12.5mg)
- atenolol (50mg)
- ramipril (5mg)
- simvastatin (20mg) to lower cholesterol
- aspirin for thinning the blood (100mg)
These include aspirin, a statin, three blood pressure-lowering drugs, and folic acid.
It was, in part, a ‘non-inferiority’ trial, which means that it firstly tested whether the Polycap was no worse at improving risk factors than each drug given separately. Once the non-inferiority of the Polycap combination was confirmed, it was compared with pills containing one drug, two drugs and three drugs to observe the effect of different polypills.
The researchers recruited 2,053 people without cardiovascular disease from 50 health centres across India. The participants were aged 45 to 80 years old, and each of them had one risk factor, which included either type 2 diabetes, high blood pressure (more than 140mm Hg systolic or 90mm Hg diastolic), being a smoker within the past five years, having a large waist-to-hip ratio (a measure of abdominal obesity), or having abnormal lipids (LDL-cholesterol more than 3.1mmol/L or HDL-cholesterol less than 1.04mmol/L).
The participants were also not taking any of the study drugs, or they had more extreme levels of risk factors, abnormal liver function, asthma or were pregnant.
The participants were randomly split into nine groups, and each group were given a different treatment for 12 weeks. Of these, 412 were randomised to one Polycap daily. The other eight groups took other combinations of the constituent drugs in a similar capsule, to allow comparison. These other groups took identical-looking capsules containing one of the following:
- Hydrochlorothiazide and ramipril
- Hydrochlorothiazide and atenolol
- Ramipril and atenolol
- Hydrochlorothiazide, ramipril and atenolol
- Hydrochlorothiazide, ramipril, atenolol and aspirin simvastatin
After obtaining written informed consent, there was a three-week lead-in period while the participants’ condition at the beginning of the trial was recorded. The researchers then recorded the participants’ blood pressure and heart rate to test for the effects of medication to lower blood pressure. The participants also had blood tests for LDL-cholesterol, and a urine test for the antiplatelet effects of aspirin.
Records were made at four, eight, twelve and sixteen weeks. The rates of discontinuation of drugs was also recorded as a safety measure.
The researchers analysed the nine groups according to the groups that they had been originally allocated.
What were the results of the study?
The results were reported for the nine different formulations. The main result was that groups taking the Polycap had a reduction in systolic blood pressure of 7.4mmHg and diastolic blood pressure of 5.6mmHg. The blood pressures achieved were lower than in groups that did not receive drugs to lower blood pressure.
The blood pressure reduction was the same whether aspirin was included in the Polycap or not. The more blood pressure drugs were used, the greater the reductions in blood pressure (2.2/1.3mm Hg with one drug, 4.7/3.6mm Hg with two drugs, and 6.3/4.5mm Hg with three drugs).
The Polycap reduced LDL cholesterol by 0.70mmol/L, which was less than taking simvastatin on its own (0.83mmol/L, 0.72–0.93; p=0.04). Both these reductions were greater than that in the groups that were not given simvastatin.
The Polycap was no worse than the other combinations that contained aspirin in terms of showing the antiplatelet (blood thinning) effects of aspirin.
Tolerability of the Polycap was similar to that of other treatments, and there was no evidence that increasing the number of active components in one pill increased intolerability.
What interpretations did the researchers draw from these results?
The researchers simply say that the Polycap formulation “could be conveniently used to reduce multiple risk factors and cardiovascular risk”. They also say that they are unable to clarify why the Polycap was less effective at lowering LDL-cholesterol than when the statin, simvastatin, was used alone.
What does the NHS Knowledge Service make of this study?
This important study has been widely reported because it is the first to have tested the multiple effects of a combination pill for reducing heart and stroke risk factors in people without known cardiovascular disease. The researchers emphasise that it cannot be assumed that the effects of any type of polypill are equal to the effects of its individual components, and that each polypill needs testing individually.
This study has demonstrated that combination pills can reduce risk factors for heart disease and stroke to a similar extent as the component medications. Whether or not these pills fulfil the potential to reduce mortality from strokes and heart disease will need to be clarified with further research.
There are a few other points to note:
- Other groups of researchers around the world are investigating polypills with different formulations. Each formulation would need to be tested individually to assess its pharmacological properties.
- The researchers say that because this formulation containing 20mg of simvastatin did not reduce cholesterol as well as simvastatin on its own, it may lead to combination pills that contain alternative doses or alternative statins.
- As the study was carried out in India, it is not known whether the drugs studied would have a similar effect on other ethnic groups.
The researchers calculate the expected reduction in risk of stroke and heart attack based on the improvement in risk factors (cholesterol, blood pressure and platelet function) shown in their trial by multiplying the risk ratios together. This gives an expected reduction of 62% in the rate of coronary heart disease and 48% in the rate of stroke, over five years. However, it is not yet known if this reduction can be achieved in practice.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
BBC News, 31 March 2009
Daily Express, 31 March 2009
Daily Mirror, 31 March 2009
The Independent, 31 March 2009
The Guardian, 31 March 2009
The Daily Telegraph, 31 March 2009
Links to the science
The Lancet 2009; early online publication: March 30