Behind the headlines – the Aspirin Component of the Physicians’ Health Study
Led by Dr. Charles Hennekens, the Steering Committee of the Physicians’ Health Study was charged with investigating the effect of aspirin on the risk of a person suffering a first cardiovascular event. Beginning in 1982, extensive preliminary screening eliminated individuals who had any of the following medical conditions:
Heart attack, stroke, transient ischemic attack (mini-stroke), cancer, liver or kidney disease, stomach ulcer or gout. Other exclusionary conditions included persons sensitive to aspirin or those currently taking aspirin.
Screening reduced a population of 59,285 willing participants to a final selection of 22,071 healthy male physicians ranging in age from forty (40) to eighty-four (84). The test subjects were divided into four groups of equal size:
- Group A took 325 milligrams (mg) of Bufferin every other day and 50 mg of beta-carotene on alternate days.
- Group B took 325 mg of Bufferin every other day and a placebo (in place of beta carotene) on alternate days.
- Group C took a placebo in place of Bufferin every other day and 50 mg of beta carotene on alternative days.
- Group D took placebos in place of both Bufferin and beta carotene.
A total of 11,037 physician volunteers took Bufferin and 11,034 received a placebo. It should be noted that Bufferin contains aspirin but is not pure aspirin. Bufferin is a compound that includes calcium carbonate and magnesium oxide – added to moderate stomach acidity and the irritation that aspirin is known to cause.
The headline: A 44 percent reduction in risk among physicians taking Aspirin!
Sixty months later as reported in the July 20, 1989 New England Journal of Medicine:
“Aspirin reduced the risk of first myocardial infarction by 44 percent… There were too few strokes or deaths upon which to base sound clinical judgment regarding aspirin and stroke or mortality… Beta-carotene produced neither benefit nor harm.”
Let’s take a look behind the headlines
There were a total of 139 heart attacks in the Bufferin group; 239 in the placebo group. If we attribute the difference (100) to a beneficial effect of aspirin – or was it magnesium in the Bufferin – we could conclude that 100 heart attacks were prevented by Bufferin. Thus the fraction of the Bufferin group that benefited is 0.00906 (100 people who did not have a heart attack divided by 11,037, total number of Bufferin takers).
Less than 1 percent of Bufferin-takers benefited (0.906 percent). Although 99 percent in the Bufferin group received no benefit at all – the final report and media reported a 44 percent reduction in risk of a heart attack among Bufferin-takers. So how did the researchers produce the headline-grabbing 44 percent risk reduction?
They took the number of people who didn’t have a heart attack because of taking Bufferin (100) and looked at it as a percentage of the number of people who did have a heart attack and didn’t take Bufferin (239). The less than 1 percent of Bufferin-takers who actually benefited are the same 44 percent who benefited from a “risk reduction among those who had heart attacks.”
This is the magic of relative risk statistics; taking unimpressive results and making them look nothing less than spectacular. This is how most drug study benefits are reported (and increasingly how nutritional supplement study benefits are reported). The lesson here is not – “don’t take aspirin” – that’s for you to decide – but to be on guard for relative risk statistics that turn a very small absolute benefit into a spectacular “risk reduction” benefit that can be used to promote and sell drugs.
The total number of deaths in both groups was the same!
Of the 22,071 study participants – those who took Bufferin and those who took a placebo – there were 88 cardiovascular deaths; 44 in each group (only 0.4 percent of the participating physicians died). As noted above, this healthy group of physicians fared much better than expected. The average number of deaths in a group of men in this age range over 60 months would have been much higher – 3.3 percent or about 700 deaths.
While those taking Bufferin suffered fewer first heart attacks and fewer fatal heart attacks, the reduction was exactly offset by a higher mortality from stroke, ischemic heart disease, sudden cardiac death and other cardiovascular events in the Bufferin group. (There were a total of 119 strokes among Bufferin-takers and only 98 in the placebo group.)
Conclusion: While the “relative risk” headlines of the Physicians Health Study promoted a surge in the use of aspirin, the “absolute benefit” of 11,037 physicians taking a buffered compound of aspirin during a 60 month period in the 1980s was – at best – quite small.
This link takes you to Harvard’s Physicians Health Study site: http://bit.ly/bfHn8w
Category: 'Bad' Science