Polypill and Minipill: ‘Miracle’ tablets or plain hype?

Years ago fixed drug combinations started mushrooming in the market as Pharma companies in their quest for newer products — and often to beat price control — began to mix and match ingredients into a single molecule to market them as newer remedies. The Health Ministry hitherto banned 344 fixed drug combinations as their use proved detrimental. 

Paradoxically, for over a decade, doctors have been dreaming of having a single daily pill combining aspirin, cholesterol medicine and blood pressure drugs - everything people need to prevent heart attacks and strokes in a cheap, generic form. This dream became a reality with the advent of the so-called “Polypill”.

The “Polypill” concept for prevention of cardiovascular disease received a shot in the arm with the results of a multi-centre trial jointly carried out by Indian and Canadian scientists, published in the ‘Lancet’ years ago. Doctors who conducted the research (on Indians) were over-excited about their findings: “patients suffering from (or at risk of cardio-vascular diseases) benefit from the 5-in-1 wonder with no greater incidence of side effects.”

The ‘Lancet’ multi-centre study tested the polypill on 2,053 Indians aged 48-80 years who did not have heart disease. They had a single risk factor like raised BP, diabetes, obesity or smoking. When the pill was given to this population – the study concluded - it had the potential to reduce risk of heart disease by 62% and of stroke by 48%.  

What is Polypill? It is a single pill that contains five life-saving drugs to combat bad cholesterol, high blood pressure and clotting, at one go.  Its ingredients are 1) STATIN, to lower levels of blood cholesterol. 2) ASPIRIN, to thin blood. 3) BETA-BLOCKER, to reduce the effect of harmful adrenaline on the heart. 4) ACE INHIBITOR, to lower the levels of an enzyme that can raise blood pressure. 5) DIURETIC, to bring about salt and water loss from body to lower blood pressure.

The ‘Lancet’ study gave us many reasons to be happy: 1) First, the convenience and psychological advantage of having to take one preventive pill instead of five. 2) Second, since the trial was conducted in Indian population we didn’t have to extrapolate data from foreign studies. 3) Third, the experimental combo super-pill seemed really effective in decreasing the incidence of strokes and heart attacks with no greater side effects.

But soon we became aware of the drawbacks of the ‘Lancet’ study (and the polypill). 1) The Indo-Canadian was a small study just 12 weeks long. 2) Multiple drugs did not allow doctors the flexibility in modifying drug combinations to suit individual patients. 3) Five medicines rolled into a single pill could, despite all, mean five times more side effects. 4) In fixed-dose combinations, evidently, some people would get more drugs than they need, others would get too little. “One-size-fits-all” turned out to fit very few.  5) Polypill never secured wholehearted FDA approval; establishing proper doses of ingredients in the polypill became a regulatory nightmare. 

Many doctors also held the viewpoint that the “miracle-pill” or “magic bullet” was nothing more, or nothing less, than uncalled-for “shotgun therapy” – to further the interests of pharma companies. Predictably, Indian pharmaceutical companies lost no time in introducing “drug combos” in spite of the fact that current evidence is not strongly supportive of the polypill hypothesis.

Even as we found ourselves engaged in a debate over the “polypill” here’s a brand new Lancet study which claims that a new “ultra-low dose pill” is 100% effective in lowering BP. High blood pressure -- which affects around 1.1 billion people worldwide -- is one of the major risk factors for heart attack, stroke, dementia and kidney disease.

Researchers from the University of Sydney in Australia, prescribed a “quadpill” -- a single capsule containing four of the most commonly used blood pressure-lowering drugs each at a quarter dose (irbesartan 37.5 mg, amlodipine 1.25 mg, hydrochlorothiazide 6.25 mg, and atenolol 12.5 mg) -- or a placebo to 18 patients in Sydney over four weeks.

The results revealed that “100 per cent of patients in the trial saw their blood levels dropping below 140 over 90, whereas just 33 per cent of patients on the placebo could achieve this.  In this small experiment blood pressure control was achieved for everyone." 

Patients who consume the commonly available hypertension-lowering drugs singly at prescribed doses experience side-effects which can vary from swollen ankles to kidney abnormalities depending on the type and class of the drug. However, “the new pill has no such side-effects”, the researchers said.

We know that high blood pressure is a precursor to stroke, diabetes and heart attack. The need for even lower blood pressure levels than we often achieve has been widely accepted in the last few years. So this could be an incredibly important step in helping to reduce the burden of disease globally. Will the study prove its worth in the long run? Sit expectare et videre!

Earl Wilson poignantly wrote, “One way to get high blood pressure is to go mountain climbing over molehills.” For those of us prone to be over-reactive and histrionic even over minor issues, any medical innovation that promises control of blood-pressure with least side-effects is good news indeed. Let’s hope the latest Lancet study withstands the test of time.

(Dr. Francisco Colaço is a seniormost consulting physician, pioneer of Echocardiography in Goa.)