ISIS 2 study: Use of aspirin to prevent cardiovascular problems

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Published: 27 Nov 2013
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Dr Conrad Keating - University of Oxford, UK

Dr Conrad Keating talks to ecancer at the 2013 Aspirin Foundation meeting in Oxford about the ISIS-2 study, which examined the use of aspirin in preventing heart attacks and additional cardiovascular problems.

Aspirin Foundation Meeting 2013

ISIS 2 study: Use of aspirin to prevent cardiovascular problems

Dr Conrad Keating - University of Oxford, UK


ISIS-2, this study that was published in 1988 looked at what we could do to people who had a first heart attack and how we could stop the second one coming. This was the collaboration, international collaboration, in sixteen countries involving 18,000 patients and it became a template for the conduct of randomised controlled trials in the future. I got involved in the study because I wrote the biography of Sir Richard Doll, the great British epidemiologist, and one of the things you notice as a historian there are so many good stories in the history of science. I was talking to a colleague and he said, ‘Look, the ISIS-2 trial with Richard Peto ran in the 1980s, it was such a fundamental trial, it used big numbers and got great results.’ So I thought, right, I’ll write a social history of this trial because all of the people involved are still alive and still sentient and it will be a chance to put my arms around this great subject that actually changed clinical practice. Most doctors’ work today, they don’t really affect that many patients beyond those that they actually see, but here was a chance for epidemiologists to do something without seeing patients themselves and actually give other doctors good knowledge about how to treat this disease of myocardial infarction, heart attack.

What used to happen in the 1980s if someone like myself had a heart attack, I’d be taken to hospital and given pain killers and the cardiologist would wait to see if I went into a lethal arrhythmia and then they’d shock me out of it, that was the treatment. So this study which was funded by a German company who made streptokinase, they paid for a study, and the great thing about the ISIS-2 study it involved nearly 18,000 patients, it was a very simple trial and it got these patients very quickly. Within three years the trial was started and ended. Often if you look at clinical trials they run out of steam, they go on, they don’t show anything but here was one where there was great planning, it was led really by Peter Sleight, the Oxford Professor of Cardiology, and he really provided the kind of excuse that other cardiologists needed to collaborate. Rather than working with boffins or statisticians they knew if Sleight’s involved it must be a good study. So because of that he led it but it was the other boffins and nerds who actually ran the study and then were able to interpret the evidence.

Of course from the point of view of today’s meeting the ISIS-2 study was three studies, really, one was streptokinase, one was aspirin and one was an epidemiological study. So it was the first study, really, that showed the benefit of aspirin. If people were given aspirin in the immediate aftermath of a first heart attack then their rate of having a second one went down by 20%, with streptokinase it went down by 40%, so it completely changed clinical practice. And, of course, the treatment regime is very cheap. So we have cheap treatments that really worked so in that way it was a tremendous template for clinical trials. In that way, when one looks at the history of clinical trials now, ISIS-2 stands out like Everest in the Himalayas.