There are few phrases more dangerous in medicine than “it stands to reason,” because what stands to reason may in fact not be a good idea, however brilliant it may once have seemed. This is because reality is always more complex than our theories about it; grey is theory, said Goethe, but green in the tree of life.
Perhaps the greatest single intellectual advance in the medicine of the last century was the realization that “it stands to reason” is no reason at all; everything must be studied in the light of experience. There was a good example of this necessity in a recent edition of the New England Journal of Medicine, which studied the effect of giving patients doses of aspirin or clonidine before and after undergoing non-cardiac surgery.
One of the most serious and feared complications of such surgery is heart attack, especially as the age at which people are operated on has increased. There are good theoretical reasons for believing that either aspirin or clonidine, or both, given peri-operatively might reduce the rate of heart attack in the first month after operation. Aspirin prevents the blood platelets from sticking to one another and the lining of the blood vessels, agglomeration of platelets being one of the mechanisms of heart attack; clonidine blocks the activity of the sympathetic nervous system whose overactivity is thought to be another such mechanism. Therefore it stands to reason, if anything does, that making the platelets less “sticky,” or the sympathetic nervous system less active, before, during and after operation might reduce the rate of post-operative heart attack. But does it?
A large trial was conducted in 135 hospitals in 23 countries, comparing the rates of heart attacks of people given aspirin, clonidine or placebo before and after operation. 10,010 patients were recruited in all, and the rate of follow-up was so high (99.9 percent) that it resembled the results of a Soviet-era election. Surprisingly, more than 40 percent of the patients were already taking low-dose aspirin prophylaxis when they entered the trial; but they were treated in exactly the same fashion as their peers who were not on aspirin.
The researchers found that neither aspirin nor clonidine reduced the number of heart attacks among the patients operated upon, nor their death rates. Aspirin did, however, significantly increase the number of patients with serious post-operative bleeding and clonidine increased the number of people suffering from episodes of significant low blood pressure.
So what had stood to reason turned out in fact not to be the case. Why? After all, trials have shown that people who take low dose aspirin are protected from heart attack. (Aspirin, cheap and humble, often seems like a panacea: there is hardly any disease it has not been claimed to prevent.)
The possible reasons why what stood to reason turned out not to be the case are various. The pathogenesis of post-operative heart attack might be different from other kinds of heart attack; or the drugs, aspirin clonidine, might have both positive and negative effects that cancel each other out. Thus aspirin might have saved some people by reducing the stickiness of their platelets, but harmed others by increasing their propensity to bleed, which in turn increased the likelihood of a heart attack. Similarly with clonidine, some might have been saved by blocking of overactivity of the sympathetic nervous system, but others might have had a heart attack because of the low blood pressure the drug caused. What the drugs might have done is give different people heart attacks, in total number the same.
So, where the prevention of post-operative heart attack is concerned (7 percent of the 10,000, incidentally, operated on), it is back to the drawing board. It stands to reason.
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Image via shutterstock / Shane Maritch / Lightspring
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