Download Polypill: A Means to Live Longer?

SCIENCE & TECHNOLOGY
Polypill: A Means to Live Longer?
By Max Sherman
In a New York Times editorial several years ago,
William Safire wrote an essay entitled, “Why Die?”1
According to the writer, nothing makes the
weak strong or the fearful brave as much as
the body’s innate drive to stay alive. His point
was that the genetic clock is set to run no more
than 120 years, although many people would
like to live much longer. A government report
summarized the will to survive, noting that the
inevitability of aging and the specter of dying
have always haunted human life, and the desire
to overcome age has long been a human dream.2
There are, of course, a number of suggestions for living longer. Among them are eating a
balanced diet, consuming less fat from meat and
dairy, focusing on fruits and vegetables, exercising daily, reducing stress and having routine
medical checkups. All of the suggestions are
important.
Whatever the regimen, it should be one
that prevents the major causes of premature
death: heart disease and stroke.3 Some experts
believe such a regimen could include taking
multiple drugs. It may even be more advantageous to combine all of the recommended drugs
into a single pill, a magic bullet to extend life
expectancy.
Remarkably, there is a product that may
meet this requirement. Unfortunately, it is not
available in the US.
It is, however, well known in the UK, where
it is described as the “Polypill.” The combination
drug was first proposed in 2003 by cardiologists
Nicholas Wald and Malcolm Law of Queen Mary
University of London.4 They summed up the preventive effects of a generic beta blocker, diuretic,
aspirin, an ACE inhibitor, folic acid and a statin
and concluded that combining the low doses of
all six into a once-a-day pill would lower cholesterol and blood pressure.
According to Wald and Law, the combination of drugs would decrease the incidence of
cardiovascular disease in at-risk patients by up
to 80%.5
Constituents and Early Results
One of the drugs being studied, the Polycap,
contains simvastatin (a statin), 20 mg; thiazide
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(a diuretic), 12.5 mg; atenolol (a beta blocker), 50
mg; ramipril (an ACE inhibitor), 5 mg; and aspirin, 100 mg.
Statins are used to lower cholesterol.
Thiazides are diuretics and stimulate the flow of
urine. Beta blockers block the effects of sympathetic activation and help the heart to beat with
less force. Angiotensin converting enzyme (ACE)
inhibitors lower blood pressure and help keep
blood vessels open. Aspirin is used for its effects
on platelets to reduce blood clots.
In a Phase II trial conducted in India,
Polycap lowered blood pressure, reduced concentrations of low density lipoprotein (LDL)
cholesterol, and impaired platelet activity to
broadly the same extent as its components. The
only unexpected result was that Polycap was not
quite as good as simvastatin alone at lowering
LDL cholesterol concentrations.
The drug seemed to be well tolerated and no
serious side effects emerged.6 In November 2011,
the company will launch a five-year, Phase III
study with 5,000 patients who are at low risk of
cardiovascular disease. In another 12 week, placebo-controlled study conducted in the UK with
378 patients at high risk of CVD, the investigators estimated a 60% reduction in heart disease.7
The same investigators are currently following
patients in several countries for longer periods.
The Premise
The rapidly increasing financial and socioeconomic global burdens of cardiovascular disease
call for interventions that have a populationwide effect as well as ones that identify and
protect individual patients who have a high risk
of major adverse events.
This is especially true in low- and middleincome countries, which can ill afford the huge
losses in human and financial resources that will
result from unchecked development of clinical
disease.8 Despite their potential for saving lives,
the drugs used in the Polypill have not been
used optimally in developed countries.
Poor adherence to multidrug regimens is
a common barrier to effective therapy almost
everywhere. Moreover, the availability of most
of these drugs in generic form would reduce the
cost of the Polypill. Economic analyses suggest
that such multidrug regimens would be quite
cost effective in reducing the burden of cardiovascular disease.
The Pitfalls
One of the drawbacks is patients’ complacency.
In other words, patients rely on the pill rather
than adhering to a healthy lifestyle. And, of
course, it is imperative that the Polypill’s value
be clearly demonstrated through long-term clinical studies rather than simply assuming that it
works.
There are also difficulties in conducting
studies. In the UK, for example, cardiovascular
screening requires participants in the placebo
group with problems identified by baseline
tests to get some treatment, making it harder to
show the Polypill’s effects.9 The US Food and
Drug Administration (FDA) requires evidence
of efficacy in populations with low risk as well,
perhaps as evidence that each component of the
Polypill adds something important.10
There are also side effects to consider,
i.e., aspirin-induced bleeding. In the study
mentioned above, about one in six patients
experienced a side effect in the short term. Most
were mild, but about one in 20 patients overall
stopped treatments due to side effects, indicating that treatment is best targeted to those at
elevated risk of disease.11 Side effects may take
five to seven years to emerge.12
Even though the drugs used are generic,
there are doubts as to whether developing
countries could afford to provide them broadly
to everyone over 55 years of age. Cardiologists
are critical of the one-size-fits-all treatment of
patients who may not be at risk.
Many physicians want to be involved in
personalized care.13 At least one blogger notes
that the Polypill may keep patients away from
doctors and hospitals. According to the writer,
not all patients are ready to assume self-care and
autonomy and he is against medicalization. This
is a term defined as the process by which health
or behavior conditions come to be defined and
treated as medical issues, and thus come within
the purview of doctors and other healthcare professionals to engage with, study and treat.14
Final Thoughts
According to Science News Daily, the Polypill
will be available soon in India, then elsewhere
within a few years, based on regulatory timelines
within each individual country. That may not be
true in the US, where it is more difficult to gain
approval for combination drugs.
However, there may be an alternative: the
polymeal, a safer, non-pharmacological, natural
and tastier choice. The polymeal combines seven
food components in a healthy diet: chocolate,
wine, fish, nuts, garlic, fruit and vegetables.
All are known to have a positive effect on
cardiovascular disease enjoyed by humankind
for centuries. The combined meal could reduce
heart disease by more than 75% based on the
Framingham heart study and the Framingham
offspring studies used to build life tables to
model the benefits of the polymeal in the general
population from age 50.15
References
1. Safire W. Why die? New York Times. January 1, 2000.
2. Beyond Therapy: Biotechnology and the Pursuit of
Happiness. President’s Council on Bioethics. October, 2003.
3. Watts G. What happened to the Polypill? BMJ.
2008;337:786.
4. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326:1419-24.
5. Reardon S. Experts debate Polypill: a single pill for global
health. Science. 2011;333:181.
6. Indian Polycap Study: Effects of a Polypill (Polycap) on
risk factors in middle-aged individuals without cardiovascular disease: a phase II, double blind randomized trial.
Lancet. 2009; 373(9672):1341-51.
7. Op cit 5.
8. Reddy KS. The preventive Polypill—much promise, insufficient evidence. NEJM. 2007;356(3):212.
9. Op cit 3.
10. Smith R. Take forward the Polypill idea, concludes expert
committee. BMJ. 2005; 330:8.
11. Polypill halves predicted heart disease and stroke risk,
study suggests. Science Daily. May 25, 2011.
12. Op cit 5.
13.Ibid.
14. Smith R. The Polypill is about demedicalisation not medicalisation. BMJ Group Blogs. 1 May 2009.
15. Franco OH, et al. The Polymeal: a more natural, safer
and probably tastier (than the Polypill) strategy to reduce
cardiovascular disease by more than 75%. BMJ. 2004;
329:1447-50.
Author
Max Sherman is president of Sherman Consulting Services
in Warsaw, IN. He can be reached by email at maxsherman@
kconline.com.
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