Peter Chow: A Polypill For All?

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The American Heart Association (AHA) reports that “the incidence of the leading cause of death, Cardiovascular Disease (CVD) in US men and women is ~40% from 40–59 years, ~75% from 60–79 years, and ~86% in those above the age of 80.”

According to the Heart and Stroke Foundation of Canada, “9 in 10 Canadians have at least one risk factor for heart disease and stroke.”

“Almost 80% of premature heart disease and stroke can be prevented through healthy behaviours, like eating healthily, exercising regularly and being active and living smoke free.”

But, it has been apparent for some time that preventative medications can help prevent premature heart disease and stroke even more.

Should everyone over 50 be taking low-dose 81 mg aspirin, ASA, to prevent heart attack and stroke?

The debate rages on in medicine.

 

Your doctor will prescribe daily aspirin therapy if:

– You’ve already had a heart attack or stroke.

– You haven’t had a heart attack, but you have had a stent placed in a coronary artery, you have had coronary bypass surgery, or you have chest pain due to coronary artery disease (angina).

– You’ve never had a heart attack, but you’re at high risk of having one.

-You have diabetes and at least one other heart disease risk factor — such as smoking or high blood pressure — and you’re a man older than 50 or a woman older than 60.

The use of aspirin to prevent heart attacks in people with diabetes but with no other risk factor, however, is controversial.

It’s a no-brainer for people at increased risk of a heart attack or stroke unless they are also at high risk of aspirin’s side effects.

 

Should every person with a strong family history of coronary artery disease take daily aspirin?

Should every person with obesity, hypertension, elevated cholesterol or high homocysteine levels take aspirin?

Should every smoker take aspirin?

Should every person with a coronary calcium scan that shows calcified plaque buildup inside their coronary arteries?

Should every diabetic??  –   A diabetic has the same risk for a heart attack as someone who has already had a previous heart attack.

 

Aspirin reduces a person’s risk of heart attack and stroke.

And most people at risk don’t know it.

That’s why some doctors suggest that it would be an overall benefit if everyone over 50 (who otherwise had no contraindications) simply went ahead and took an 81 mg baby aspirin every day.

Over half of people over 50 are at increased risk of heart attack and stroke, and aspirin would be beneficial.

But people over 50 also are at risk of intestinal bleeding if they take aspirin every day.

Aspirin roughly doubles the risk of upper gastrointestinal bleeding from  hemorrhagic gastritis or a bleeding ulcer.

Which risk is worse?

It’s a matter of weighing the benefits and harm.

The benefits of aspirin are reducing harm and death from heart attack and stroke.

The risk from aspirin is an upper gastrointestinal bleed that may lead to a stay in hospital and a blood transfusion.

Unlike heart attack or stroke, a GI bleed in this day and age is unlikely to be fatal or cause chronic/permanent disability.

While daily aspirin can help prevent a clot-related stroke, it may increase your risk of a hemorrhagic stroke, a stroke caused by bleeding in the brain.

But, the vast majority, 87%, of all strokes are ischaemic, caused by blockage of an artery, which aspirin could prevent.

Only 13% of all strokes are hemorrhagic, which aspirin could precipitate or exacerbate.

A fixed-dose 3 drug combination of aspirin, a statin (to lower cholesterol) and an ACE inhibitor (cardioprotective and anti-hypertensive) into a single pill, was proposed by the WHO as one strategy to reduce the global burden of CVD by up to 80%, given its potential for better adherence and lower costs.

The editor of the prestigious British Medical Journal, opened his June 28, 2003, editorial with this teaser:

“It’s perhaps more than 50 years since we published something as important as this cluster of papers.”

Intrigued readers pored over the papers, which described a medication that “would have a greater impact on the prevention of disease in the Western world than any other single intervention.”

The intervention turned out to be a combination of cardiovascular drugs with an unusual strategy of delivery:

The medication was called the Polypill, a combination of 5 cardiovascular medications—a statin (cholesterol lowering), an ACE inhibitor (antihypertensive/cardioprotective), a beta-blocker (antihypertensive/cardioprotective) and a thiazide (an anti-hypertensive/diuretic) —as well as aspirin (clotting inhibitor).

The study envisioned that everyone over age 55, the population segment accounting for 96% of all deaths from coronary artery disease and stroke, would take the pill every day for the rest of his or her life.

 

If all complied, 88% of heart attacks and 80% of strokes would be prevented, said the authors, who also opined that physicians need not be involved.

And if in 2003 the Polypill was just a theory, at the World Congress of Cardiology in Barcelona, the World Heart Federation president announced that a version of the Polypill would be introduced in Spain by 2009, while investigators in New Zealand and Australia were about to begin trials on alternate versions of the pill.

The Polypill idea was radical, because physicians generally prescribe cardiovascular medications to healthy people only if they are at extremely high risk.

But proponents contend that anyone living in the Western world today falls into the high-risk category and needs to reduce each of many cardiovascular-disease risk factors, not just the one or two surpassing some arbitrary threshold.

Otherwise, those proponents warn, many of us could become part of the third of the population who die from an almost completely preventable disease.

A study, named PolyIran, published in the Lancet in August 24, 2019, was based in more than 100 villages in Iran and about 6,800 people took part.

The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, a statin, a thiazide diuretic, and either enalapril (an ACE inhibitor) or valsartan (an ARB or Angiotensin Receptor Blocker) for primary and secondary prevention of cardiovascular disease.

Half the people were given the polypill and advice on how to improve their lifestyle, with the other half just getting the advice.

Two formulations of polypill tablet were used in this study.

One formulation contained hydrochlorothiazide 12·5 mg (diuretic/antihypertensive), aspirin 81 mg, atorvastatin 20 mg (cholesterol lowering statin), and enalapril 5 mg (ACE inhibitor – antihypertensive/cardioprotective).

Participants who developed cough from the ACE inhibitor  component switched to polypill two, which included valsartan 40 mg instead of enalapril 5 mg.

6,838 individuals were enrolled into the study—3,417  in the minimal care group and 3,421  in the polypill group, followed for 5 years.

The primary outcome—occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)—was centrally assessed by the study team.

301 (8·8%) of 3,417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group.

The polypill group had 1/3 fewer cardiac events.

The frequency of adverse events was similar between the two study groups.

There were 10 intracranial haemorrhages in the polypill group and 11 in the minimal care group.

There were 13 upper gastrointestinal bleeds in the polypill group and 9 in the minimal care group.

The idea of the polypill has been around since 2001 but this was the first major trial to prove its effectiveness.

The subsequent polypill, produced in Iran by an order from the  Imam Khomeini, was designed 14 years ago and called “PolyIran”.

The Population Health Research Institute (PHRI), a joint institute of McMaster University and Hamilton Health Sciences conducted an international study, TIPS-3 (The International Polycap Study- 3),  which evaluated the efficacy and safety of the polypill, Polycap, as compared with a placebo.

The study followed 5,714 people with no previous heart disease or stroke, but at intermediate risk, men over 50 and women over 55, in 89 centers from nine countries for an average of 4.6 years and was published in The New England Journal of Medicine in January 21, 2021.

Polycap (Cadila Pharmaceuticals of India) is a polypill consisting of 40 mg simvastatin (cholesterol lowering statin); 100 mg of atenolol (beta-blocker antihypertensive/cardioprotective); 25mg of hydrochlorothiazide (diuretic/antihypertensive), and 10 mg of ramipril (ACE inhibitor – antihypertensive/cardioprotective).  75 mg of aspirin, ASA, (to inhibit blood clotting) was added separately.

The polypill (Polycap) plus ASA reduced the risk of major cardiovascular events including heart failure, stroke,resuscitated cardiac arrest, angioplsty or coronary artery bypass surgery by almost 30%.

The combination of the polypill (Polycap) plus aspirin administered for a mean of 4.6 years in a primary-prevention population at intermediate risk led to a reduction in death from cardiovascular causes, myocardial infarction, or stroke, by 32%.

The polypill tested in this trial is available in India and in a few countries in Africa.

There are different polypills available in Europe, South America and South Korea, and new polypills are being developed in North America and China.

Polypills are easier for patients, who don’t have to juggle fistfuls of daily medications, increasing compliance, and for doctors who’d only have to write one prescription.

A single pill also is cheaper to market and distribute.

The fact that the component medications in a polypill are generic is a double-edged sword, because no Big Pharma company is willing to invest a lot of money in developing and marketing a polypill.

It may require either health insurance companies or governments or charitable organizations to develop polypills.

The potential implications in terms of CVD burden around the world, particularly in low- and middle-income countries, are huge, especially if the polypill is inexpensive.

The Polycap in India costs approximately USD$15 per month.

The polypill, given in addition to lifestyle modification, would be part of a comprehensive strategy for the prevention of cardiovascular diseases, the world’s leading cause of death.

As noted already, no Big Pharma company is willing to invest a lot of money in developing and marketing a polypill, because all of the components are generic.

Health Canada and the Heart and Stroke Foundation of Canada could get together and develop a Canadian polypill, as the government of Iran did with their PolyIran pill and India did with their Polycap.

Or, Canada could make a deal with Cadila Pharmaceuticals of India for the Polycap capsule (only USD$15 per month!!).

We could rebrand it as POLYCAN.

Our member of parliament could initiate this, stamping his legacy forever for saving countless years of Canadian lives.

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