There is no scientific study to tell us if at all is safe to combine drugs in one poly-pill

A few years ago, the British Medical Journal wrote an editorial on the need to have a broad perspective on killer diseases like heart attacks, strokes and their risks. I was a bit confused by the editorial and the connected articles in that issue. Fiona Godlee, the editor-in-chief, and the authors of the cited articles were advocating a broad perspective in preventing cardiovascular diseases, and rightly so. However, at the same time, they were forgetting the most important aspect of the risk factors for cardiovascular diseases: the mind. Several studies, including the White Hall study, had shown that hostility, clinical depression and various other work-related stressors are risk factors. While the editor-in-chief and the contributors seemed engrossed in some of the questionable risks like cholesterol, raised sugar and arterial pressure, the vital role of the human mind was ignored.

The editorial is all about the new brahma-astra against many deadly diseases like stroke, heart attack and sudden death. The single-pill-for-life therapy is to start at the age of around 55 and go on till death! The drug, known as polypill, contains small doses of many drugs, namely, aspirin, three blood pressure (BP) lowering drugs, statins and folic acid. All the drugs are in sub-optimal doses. There is no scientific study to tell us if at all it is safe to combine these drugs in one pill. What has happened to our evidence base?

What is the basis of selecting people at the age of 55 for the pill? Many younger people die of heart attacks and stroke too. Should we not protect them also? From that point of view, it will be nice to start the polypill from birth, like the multitude of untested vaccinations that we give to kids today! I am worried about another fallout. For a healthy person aged 55, if three anti-hypertensive drugs are given unnecessarily, there is a chance of his BP plummeting. At the age of 55, most, if not all, people will have some degree of coronary artery blocks that are normal and do not produce diseases.

However, coronary filling occurs in diastole only. During sleep, these unfortunate victims’ BP could go so low that the diastolic filling in the partially blocked coronaries might get jeopardised leading to death! The multitude of possible adverse reactions of these drugs in combination could be mind-boggling. Although we have known aspirin for 350 years, we still do not know its ideal dose! That said, what of the other drugs in the polypill that haven’t stood the test of time?

All the components of the polypill are advocated in the editorial as panacea for prevention. When tested individually, even in adequate doses, it did not significantly reduce the likelihood of stroke, heart attack or death. While there were significant ‘relative’ risk reductions, the absolute risk reductions were negligible and the number needed to treat was prohibitively high, with dangerous (even fatal) adverse drug reactions. Ebrahim Shah and GD Smith went one step further to show that the ‘pooled effect’ of multiple risk-factor interventions on mortality was insignificant and very small. Professor Michael Oliver, Fellow of the Royal Society, Edinburgh, has shown that drug use for risk reduction is almost useless. GD Smith and M Egger ask a very pertinent question in their journal titled Who Benefits from Medical Interventions. All these add up to the case of the missing evidence of Sherlock Holmes. To cap it: the very basis of fat hypothesis in the causation of killer diseases is being questioned even in Western science!

All these efforts to use drugs at the drop of a hat are due to the inseparable marriage between the pharmaceutical lobby and the medical profession. In the words of one of the leaders in the field, Marcia Angell, former editor of the New England Journal of Medicine, “The ties between clinical research and industry include not only grant support, but also a host of other financial arrangements. Researchers serve as consultants to companies whose products they are studying, join the advisory boards, and the speakers’ bureaus, enter into patent and royalty arrangements, agree to be listed authors of articles ghost written by interested companies, promote drugs and devices at company sponsored symposia, and allow themselves to be plied with expensive gifts and trips to luxurious settings. Many also have equity interest in companies.” Human illness and wellness need a very broad perspective, indeed! Our present perspective will not pass the scrutiny of Sherlock Holmes.

Professor Dr BM Hegde, a Padma Bhushan awardee in 2010, is an MD, PhD, FRCP (London, Edinburgh, Glasgow & Dublin), FACC and FAMS.