What the Story of a Famous Little White Pill Says About How Medical Research Works

Twenty-five years ago this month, the New England Journal of Medicine published a special report on something that’s become medical gospel:


That’s right. Not as in “take two and call me in the morning,” but in the realm of the randomized double-blinded placebo-controlled trial. Or what we generally consider the gold standard of evidence in medical research.

If you’ve often heard that bit of jargon but always wondered why it’s so exalted, break it down:

  • randomized: the assignment of the treatment (aspirin) or placebo (‘inert’ sugar pill) is not given in any planned sequence.
  • double-blinded: neither the researchers nor the subjects know who is taking what (everything is coded so that analysts can find out at the end).
  • placebo-controlled: the study compares the treatment against placebo to see if it’s helpful or harmful.

Even though acetylsalicylic acid’s properties as a pain reliever and fever reducer had been known in the time of Hippocrates, it was in 1899 that Bayer first patented and marketed what came to be known as aspirin worldwide.

A mere 89 years later, researchers from the “Physicians Health Study” did something unusual. Citing aspirin’s “extreme beneficial effects on non-fatal and fatal myocardial infarction”–doctor speak for heart attacks–the study’s Data Monitoring Board recommended terminating the aspirin portion of the study early (the study also was looking at the effects of beta-carotene). In other words, the benefit in preventing heart attacks was so clear at 5 years instead of the planned 12 years of study that it was deemed unethical to continue blinding participants or using placebo.

Turns out that aspirin inhibits platelets, tiny specialized blood cells whose job it is to stop your cuts from bleeding. In heart attacks, platelets clump inside the arteries of the heart depriving the heart muscle of vital oxygen. Using aspirin to inhibit their function is a key mechanism of preventing this phenomenon.

The amazing thing is that it took decades to organize an elegant and simple enough study with enough power (statistical heft) to show that good ol’ aspirin could really make a difference.

And that it was “just” aspirin. Shows how far we have yet to go in building medical knowledge.

John H. Schumann, MD is a general internist and medical educator at the University of Oklahoma School of Community Medicine in Tulsa, OK . He is also author of the blog, GlassHospital (@GlassHospital), where this post originally appeared.

5 replies »

  1. Wow, this is incredible piece of information. A simple drug like Aspirin can be used to treat heart attacks is really mind blowing. Over the time, lot of money has been put into development and research of medicines which help prevent heart attack when the solution was lying just before our eyes.

    I think there has to be a extended study on this and a detailed report on the side effects discussed thoroughly and implement the use of Aspirin for heart diseases.

    This should be a very helpful solution for a lot of poor patients who have no money to treat heart diseases

  2. I think that we may be surprised at a number of possible other uses for many drugs that have been developed. Each year millions of dollars are spent developing one particular cure that is rejected by the FDA as it may not necessarily address its intended ailment, yet could potentially help with another. Looking forward to seeing what lies ahead in the decades to come.

  3. Whereas the evidence for the safety and efficacy of paper record keeping has long been dispositive and simply cannot be improved upon.

  4. This study had and continues to have far reaching impact. The evidence is solid. Aspirin is cheap, safe, effective, usable, and prevents heart attacks.

    What is the evidence that CPOE and EHR devices are safe, effective, usable, and improve outcomes and prevent adverse events? Hmmm, they are not cheap.

    Aspirin appears to be orders of magnitude more cost effective than these government mandated devices that are being deployed in an unregulated experiment.