Shortness of breath is a very unpleasant sensation and people with chronic obstructive pulmonary disease (COPD) have it chronically. It is not something that you can ever get used to, breath being so essential to life, and the disease worsens relentlessly; without medical attention one dies slowly of suffocation. That is a horrible way to die. Though COPD will become less common in time, thanks to a reduction in smoking (except in Colorado), it is still the third most common cause of death among adults in America.
As yet there is no cure and perhaps there will never be one, short of lung transplant; but it has been reported many times in the medical press that statins, drugs taken to reduce the risk of heart attack among the otherwise susceptible, ameliorate the symptoms and reduce the frequency of acute exacerbations.
Patients who have COPD and are taking statin drugs to reduce their risk of heart attack or stroke have been thought to experience fewer acute exacerbations of the disease and as a consequence to live longer. There is biological plausibility to this observation, for statins have an anti-inflammatory effect and exacerbations of COPD are caused by infection and its consequent inflammation.
In a paper published recently in the New England Journal of Medicine, researchers performed a prospective, double-blind trial of the best-known statin, simvastatin, in COPD, to see whether it really did exert a protective effect. All reports hitherto have been retrospective, and one of the great medical lessons learned in the last century was that, when it comes to evaluation of the therapeutic worth of a treatment, an ounce of prospection is worth a ton of retrospection.
Patients were recruited from no fewer than 45 centers, 29 in the U.S. and 16 in Canada. Since only 878 patients were in the end recruited, this illustrates a general principle of medical research, namely that patients who seem common as muck before a research protocol has been devised suddenly become much rarer after it has been devised.
The patients were divided into two groups, one who took the statin and one who took a placebo. They were followed up for between one and three years. All of them had a history of at least 10 pack-years: that is to say of having smoked at least one pack of 20 cigarettes a day for 10 years.
The results, unfortunately, were unequivocal: simvastatin failed to help those with COPD. They developed acute exacerbations of their disease just as quickly and seriously while they took the drug as while they took a placebo. The trial, in fact, was halted early because of its “futility,” that is to say the absence of any effect of the supposedly active drug.
An editorial by different authors that accompanied the report of the trial denied, however, that the trial itself had been futile. If it had not been performed, doctors would have continued to take retrospective reports of simvastatin’s efficacy in COPD as a reason to prescribe it; and this would have led to an immense waste of time, effort and money. Negative results are as important in their way as positive. If they don’t lead to advance, they at least prevent retrogression.
There is one intriguing question that neither the authors of the trial paper nor those of the editorial ask: how came it that the statins retrospectively seemed so efficacious in COPD? In part this was a matter of reporting bias: those clinicians who observed no such effect would not bother to report that they had not observed the effect. Second, people tend to find evidence of what they are searching for. Perhaps, also, the drug exerted a placebo effect, which is always better than nothing. Once again we have reason to thank one of the greatest discoveries in the history of medicine, that of the double-blind trial.
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images via shutterstock / Alila Medical Media / Protasov AN / Iaroslav Neliubov
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