Whatever happened to the polypill?BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j1474 (Published 27 March 2017) Cite this as: BMJ 2017;356:j1474
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To have an opinion about the polypill it would be useful to define what the polypill is and what it is supposed to be used for and for whom.
The initial promise of Wald and Law was to reduce cardiovascular events by 80% and, thus, extend the time free from cardiovascular events by 11 years by medicating all people aged 55 years or older .
This was based on the observation that in a population at an epidemiologic level lowering of some risk factors was related to fewer CV events. So reducing actively these risk factors with medication in a larger healthy population would lower CV events too and would have better results than treating only at risk population assuming that “A large number of people at a small risk may give rise to more cases of disease than the small number who are at high risk”.
The initial polypill combined six drugs: a low dose of aspirin to reduce platelet aggregation, folic acid to lower homocysteine levels, three low doses of antihypertensive drugs (the suggested combination included low doses of hydrochlorothiazide, angiotensin converting enzime inhibitors, and beta-blockers), and atorvastatin 10 mg or simvastatin 40 mg.
From the start, Salim Yusuf, a Canadian cardiologist and director of the Population Health Research institute was involved in this project and anticipated, by calculating the effects of the different combined drugs, a reduction of mortality by 75%.
After many years and studies aspirin and folic acid were discarded because of no effects or negative effects .
The question was posed about the interest of lowering blood pressure in patients with normal blood pressure. This question was challenged by the SPRINT trial that was stopped prematurely and presented as conclusive and a landmark study in order to change guidelines for blood pressure management in the healthy population. In fact this study was riddled with methodological flaws and it raised concerns about adverse effects of polypharmacy in patients at low risk for CV events. Although there were only a mean one more drug in the intensive treatment group (1,9 vs 3) the rate of serious adverse effects was double in the intensive treatment group (4,8 vs 2,5%) .
The HOPE 3 trial is not immune from critics. The trial has multiple primary outcomes, it wasn’t blinded since cholesterol was monitored and also groups taking rosuvastatine were pooled for the final analysis . It also raises concerns about adverse effects since dizziness, lightheadedness and hypotension were a cause of discontinuation of treatment for 388 patients (6,1%) in the treatment group and 212 (3,3%) in the placebo group (number needed to harm 35 in the treatment group) .
Quality of life was not assessed. This is important because the corollary for drugs that are meant not to need prescription or controls is that their prescription relies only in the fact that everyone is confident that benefits will be much greater than harms. Moreover since there isn’t any possible control for effectiveness, the drugs would be stopped only if there are adverse effects identified.
In the USA, 64,8% of people aged 65 years and over are currently taking at least three drugs . Polypharmacy has been shown to be an independent predictor for frailty in elderly people  and adverse effects are thought to be the 4th or 6th cause of death in the USA with 44 000 to 98 000 deaths every year .
There are also concerns about conflicts of interests since the studies carried out by the Population Health Research institute, with Salim Yusuf as its director, seem to have been mainly funded by pharmaceutical companies as is shown in the 2006 PHRI report.
Competing interests: No competing interests
I do hope the idea is not gaining ground, but if it is it needs to be based on proper statistics.
Anthony Viera quotes the HOPE-3 trial as showing a 29% reduction in cardiovascular events. While one might argue that it is unclear which of the polypill constituents might be responsible, he notes - in the same sentence - that the events rate dropped from 5% to 3.6%. That is not 29%. It is 1.4%. To blast an entire population with polypharmacy for the sake of such a small reduction seems absurd.
Competing interests: No competing interests