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Disclosure
None.
Anthony S. WierzbickiDepartment of Metabolic Medicine ⁄ Chemical Pathology,
Guy’s & St Thomas’ NHS Trust, St Thomas Hospital,London, UK
Email: [email protected]
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doi: 10.1111/j.1742-1241.2011.02769.x
ED ITORIAL
The Polypill – multiple drug combinations are not theanswer
It is an interesting concept – combine multiple risk-
reducing drugs in one tablet and save the world. In
this way drugs are placed ahead of lifestyle changes
(which have often failed) and as a single pill adher-
ence to medication is projected to increase and cost
decrease. This sounds too good to be true and it
almost certainly is.
The combination proposed includes an angiotensin
converting enzyme (ACE) inhibitor, statin, thiazide
diuretic, beta blocker and aspirin, and the target
individuals are those with established vascular disease
(often referred to as secondary prevention) and those
without known vascular disease but who, as a result
of multiple risk factors, are at high risk (e.g. smok-
ers, hypertensives, diabetics, hyperlipidaemics) – so-
called primary prevention.
As a concept maximising risk reduction with
minimal inconvenience to the patient is everyone’s
therapeutic goal. The problem with the Polypill as
proposed is first that it mixes drugs that titrate to
maximal effect with those with a flat dose–response
curve. Titration of ACE inhibitor, statin and beta
Editorials 1113
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, November 2011, 65, 11, 1111–1114
blocker is not possible unless multiple drug combi-
nation variables are made which will negate the cost
argument.
The second concern is adverse effects. Thiazides
are the worst treatment with regard to causing male
erectile dysfunction. They are biochemically
unfriendly elevating blood glucose, triglycerides and
low-density lipoprotein cholesterol as well as uric
acid and they may adversely affect renal function.
ACE inhibitors can cause a dry hacking cough (often
disturbing sleep), more frequently in women and
people of Chinese origin. Simvastatin is the most
lipophilic statin with the greatest incidence of central
nervous system side effects (memory loss, depression,
lack of concentration, erectile dysfunction) and
muscular aches and pains. Beta blockers may precipi-
tate well-recognised side effects such as asthma but
also lead to fatigue, generalised aches and pains, and
a ‘zombie’ like feeling. Aspirin, especially when not
soluble, may cause varying degrees of gastric
irritation.
We therefore have the possibility of ruining a man
and woman’s sex life, disturbing their day and night
with a dry hacking cough, giving them indigestion or
even gastric bleeding and then rendering them so
lethargic it does not matter anyway, with the only
good news being the simvastatin causes them to for-
get every adverse event.
The Polypill is a blanket approach to an individual
problem which needs individual management focus-
ing on quality as well as quantity of life. To live a
longer but miserable life is not a realistic approach
to reducing risk. Combination therapy is certainly a
patient-friendly form of therapy but is currently and
most effectively composed of carefully targeted drugs.
The ‘one size fits all’ strategy is more about market-
ing than medicine, and I come back to the point that
mixing non-titratable with titratable drugs is not log-
ical. Unravelling adverse effects will add to the
patients’ and physicians’ burden.
Polypill trials will continue and no doubt combi-
nations will be patented, but managing patients as if
they were numbers is the wrong way to reduce risk.
Disclosures
None.
Graham JacksonEditor
Email: [email protected]
doi: 10.1111/j.1742-1241.2011.02819.x
1114 Editorials
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, November 2011, 65, 11, 1111–1114
