From Alzheimer’s to Zebrafish: Eclectic Science and Regulatory Stories 162
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 govern-
ment 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 angiotensin converting enzyme (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 thia-
zide (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. 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 2 trial conducted in India, Polycap lowered blood pressure, reduced con-
centrations 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 3 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 esti-
mated 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 dis-
ease call for interventions that have a population-wide 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 middle-income countries, which can ill afford
the huge losses in human and financial resources that will result from unchecked
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 govern-
ment 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 angiotensin converting enzyme (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 thia-
zide (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. 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 2 trial conducted in India, Polycap lowered blood pressure, reduced con-
centrations 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 3 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 esti-
mated 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 dis-
ease call for interventions that have a population-wide 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 middle-income countries, which can ill afford
the huge losses in human and financial resources that will result from unchecked