Richard Lehman: Polypills and Roses

Last month, the first large trial of a Polypill with five-year follow up appeared in The Lancet. Called PolyIran, it was a cluster randomised trial conducted mainly in the villages of a north-eastern province of Iran bordering on the Caspian Sea. The province was redefined in 1997 and now bears the name Golestan, meaning place or land of roses, whereas from the earliest Indo-European times the region had been called the land of wolves. In a relatively untreated population, the four-ingredient polypill achieved a relative reduction in major cardiovascular events of over a third in those who claimed to be compliant. This is a very striking result, especially since recordings of blood pressure and lipids suggest that many of those who presented empty pill containers had not in fact been taking the contents.

As the world contemplates the meaning of this success, one of the investigators asked if I might try and review the study in the style of my once-regular weekly reviews of the journals. I decided to take inspiration from the name of the province where the trial took place. 

Gulistan (or Golestan) was born in the mind of the Persian poet Sa’di in the middle of the thirteenth century. For the next seven centuries, his Place of Roses (Gulistan) was the most widely quoted work of literature from Istanbul to Northern India. “Every word of Sa’di has 72 meanings” is still a popular saying in Iran. His book is a collection of stories and poems illustrating various aspects of human life from a standpoint of compassionate realism. Here’s a new one:

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“In the land of Persia there is a seldom-visited domain called the Place of Wolves, where dwells a people whose tribes once lived from the land and the sea. But a time came when the sea was poisoned by the hand of man: its fish, once numerous, delightful to the eye and heavy upon the table, now lay rotting on the shores. The land too became barren, for the sons of the land would not remain with their fathers to cultivate it, but departed to find wealth in distant cities.

The elders of Persia said among themselves, ‘Let us call this Place of Wolves the Place of Roses, Golestan, that people will once again wish to live there. Moreover, let us give them a Capsule of Longevity, which will render them free from diseases of the heart.’ Apothecaries laboured to find the finest ingredients to preserve the lives of the Golestanis, and to mix them cunningly into such capsules. And to prove that they truly worked, the elders and apothecaries decreed that some villages would receive the capsules, while others would not: and that account should be made of all that died from diseases of the heart in all the villages for a period of five years. 

So preachers from afar came to the villagers of Golestan, bidding them to abstain from fat and sugar and to smoke neither tobacco nor opium. In some villages they also distributed the Capsules of Longevity. The people wondered at this: for if they followed the advice of the preachers, what pleasures would be left to them? As for the capsules, who knew what they contained? It came to pass that none among the people followed the advice of the preachers, yet many were willing to take the capsules: for they hoped to increase the number of their days. But of those who started taking them, most grew forgetful and stopped. Nevertheless they could see that it pleased the preachers from afar if they came back to receive more. To this end they showed them empty packets in proof that they had remembered to take the capsules; and they also submitted to have their blood taken for tests.  

Now when five summers were come and gone, the preachers departed the land called Golestan, bearing scrolls whereon were written the numbers of those who had taken the capsules, and who had died or sickened during that time; and also whatsoever meanings were revealed within their blood. And when account was rendered, it was seen that most of the people who came for more capsules had not been taking them, for this was revealed in the fats of their blood. Yet among those who presented empty packets for 5 years, fewer were stricken with diseases of the heart than those who did not. But death was equal among them.

The elders and apothecaries pondered these matters and took counsel among themselves. Some among them said, ‘Let us not perplex ourselves, but rather rejoice. Let it be noised in the world that our capsules have worked and we have preserved the hearts of many in Golestan.’ But others said, ‘It is true that we have gathered wisdom and done good, yet we have not won the trust of the people despite all our preaching. Let us diligently seek ways to understand the minds of those we serve, that they may live happier and better lives howsoever long they may be placed upon the earth.’

In the villages, the people pondered. The shores of the sea receded further, and more dead fish appeared. The sheep were eaten by wolves, for the shepherds had departed. Wild roses sprang up in the untilled fields. For such is it called the Land of the Roses.”

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All men are members of the same body, Created from one essence.
If fate brings suffering to one member, The others cannot stay at rest.
You who remain indifferent
To the burden of pain of others,
Do not deserve to be called human.

The final words are those of the real Sa’di (1256), woven into a carpet which hangs in the council chamber of the United Nations.

Richard Lehman is professor of the shared understanding of medicine at the Institute of Applied Health Research, University of Birmingham.

Competing interests: None declared