Friday, May 22nd, 2009

COULD THERE BE A POLYPILL IN YOUR FUTURE?

LET’S HOPE NOT!

Imagine a pill made from many pills that could reduce heart disease by up to 80%:

1. A blood pressure lowering diuretic – hydrocholorthiazide (12.5 mg)
2. A cholesterol lowering “statin” – pravachol (20 mg)
3. A drug that lowers blood pressure, slows the heart beat and weaken the force of heart muscle contraction, reducing the heart’s need for oxygen – atenelol (50 mg)
4. A blood pressure lowering “ACE Inhibitor”  drug that offers additional heart protection – ramipril (5mg).
5. Low dose aspirin (100 mg) to prevent platelets from forming artery blocking clots and protect against heart attacks.

Cooked up by two well meaning Drs. Wald and Law at the Univeristy of London, the “polypill” would supposedly confer a total benefit based on the additive effects of its five constituent ingredients, reducing the risk of heart disease up to a nearly miraculous 80%!

Because the polypill is made up of generic drugs, the cost could run as low as $1 a month . . . at least in some countries.

It could be given to everybody over 55, regardless of risk and whether or not they already have heart disease or not.

LIP SERVICE PAID TO LIFESTYLE

Supporters are always careful to remind us that the polypill should always be used in conjunction with diet, exercise and stress reduction – or “lifestyle modifications”.

Of course, polypill proponents don’t tell us how a physician population with virtually zero training in nutrition, exercise physiology or stress management is somehow – as if by magic – going to make meaningful changes in behavior in the usual rushed 10 minute appointment.

POLYPILL “NON-INFERIOR” TO INDIVIDUAL DRUGS

A recent trial of the polypill in India, a country with a burden of disease and poverty difficult for most Americans to even begin to imagine, tested the polypill on several hundred subjects. (Lancet, April 18-24, 2009) They compared the polypill to its individual components.  They came to the conclusion that the polypill’s measured performance was “non-inferior” to the performance of its respective parts.

“Non-inferior” is a nuanced bit of terminology that basically means the new treatment – in this case the polypill – is equivalent to the standard treatment.

The Indian study only measured biomarkers – blood pressure, LDL cholesterol, heart rate and a test for platelet function.  Because it is relatively easy to tease out individual biomarker effects then compare the polypill to individually administered drugs,

DOES THE POLYPILL SAVE LIVES?

Researchers have yet to measure the benefits of the polypill in hard outcomes, or what are called “patient-oriented outcomes”.  This means no one has conducted a study to determine whether the polypill actually saves lives.  The India study simply measured reductions in blood pressure, cholesterol and platelet inhibition, not hard outcomes like heart attacks, death from heart attacks, or death from all causes.

Interestingly, the widespread use of the polypill could be expected to cut into drug company profits from high priced blockbuster drugs still under patent.

THE SIDE EFFECT SPECTRE

There are several problems with the polypill.  One of them is side effects.  Here’s a sampling:

Hydrocholorthiazide:  Depletion of important nutrients such as magnesium and zinc.  Disruption of normal glucose metabolism and the hastening of the onset of diabetes.  Zinc and magnesium depletion are probable causes of increased risk of diabetes.

Pravachol:  Muscle aches and pains.  Memory loss and depression.  Loss of libido. Peripheral neuropathy.  Depletion of coenzyme Q10.

Atenelol:  Weight gain.  Depression. Lightheadedness and fainting.  Increased risk of diabetes.  Depletion of coenzyme Q10.

Ramipril:  Persistent dry cough.  Stomach pain, nausea, vomiting, diarrhea and rash. Dizziness, fatigue, headache, loss of appetite and numbness or tingling in the hands or feet.

Aspirin.  Gastrointestinal bleeding.

Drs. Wald and Law, the originators of the polypill idea, claim adverse effects could range between 8 and 15%.  That’s up to one in six people. But in trials of individual drugs, as many as 50% of study participants have dropped out due to adverse effects.

Future testing of the polypill will afford an interesting opportunity to measure all these side effects in one pill across a wide population.  Could embarking upon such a potentially hazardous project be malpractice?

WHY EXERCISE WHEN YOU CAN TAKE A PILL?

The polypill will may cause people to abandon a healthy diet and exercise.  I once met an overweight 40 year old drug rep already on Lipitor for high cholesterol who seemed to think his dietary indiscretions were “covered” by his drug.  I’ve heard this story from other people on these drugs – mostly middle aged men – who seem to think these drugs possess magical powers of protection against all manner of self abuse – smoking, never exercising, overeating etc.

The lip service paid to lifestyle by the medical profession continues to astound me.  The realities of 10-minute appointment (or less!) primary care medicine and the utter lack of training in nutrition and exercise promote a kind of sound bite medicine wholly inadequate to the task of getting people to change their behaviors.

Buried in the Procedures section of the Lancet study cited above is this sentence: “All participants received advice about optimum lifestyles”.  No further detail supplied.

ONE-SIZE-FITS ALL MEDICINE TAKEN TO AN ILLOGICAL EXTREME

The polypill strikes me as a kind of ultimate one-size-fits-all drug study medicine fantasy.  Right now regulatory agencies require that combination drugs come in various versions that include every dose combination of each drug.  This spells trouble for a pill with four or five components each having two to four doses.

Imagine the prescribing chaos that could create!

The leading causes of heart disease remain smoking, poor diet and physical inactivity.  There is great deal more work that needs to be done in these areas.

I fear the polypill may end up being a time consuming and costly distraction.