It Just Doesn't Matter—Why Aspirin Matters
In his career-launching, persona-defining film Meatballs, a painfully funny love letter to sleepaway camp, Bill Murray as counselor Tripper coins a phrase rich in his unique brand of irony. In a rambling speech Tripper sparks the world's least inspiring chant to help his campers defeat their rich-kid rivals across the lake: "It just doesn't matter! IT JUST DOESN'T MATTER!"
Impossibly, the scene is rousing. It was reportedly improvised, and we watch in mirrored amazement as a cabin of hapless campers and counselors is lathered to a frenzy after first shaking their heads, then giggling self-consciously, and finally joining in. Indeed, we learn it matters—because it doesn't matter. Murray's sardonic genius captures the poetic beauty of heightened teenage summers, and common cause.
Which, obviously, makes one think of aspirin. Am I right?? History’s first pharmaceutical blockbuster, aspirin was cleverly trademarked in 1899 by a German dye company. Before that it was the folk remedy willow bark, a potent anti-inflammatory used for centuries to treat fever and pain. But when Bayer tweaked the active ingredient, mass produced it, and called it ‘aspirin’, the drug was an overnight sensation.
Today, with countless studies and one Nobel given just for showing how it works, aspirin is among the world’s most popular drugs for good reason. It saves lives during heart attacks, treats dozens of conditions, and it’s great for headaches.
Aspirin’s uses are so broad health experts long ago asked an obvious question: Should we all just take it every day?
Large trials from the 1970s-2000s found daily aspirin worked after heart attacks and strokes by preventing problems at about 1% per year. And while living longer due to the drug was rare at 1 in 300, major harms were even rarer.
But did you catch the caveat? While aspirin works great in the throes of a heart attack, long-term daily aspirin works only after a heart attack. That’s 'secondary prevention’, targeting people who already have heart disease. For primary prevention, people without known heart disease, aspirin caused as much harm as benefit, with no effect on deaths. In other words, it didn’t matter.
It just. Didn’t. Matter.
But people are drawn to a wonder drug. My father, for instance, despite no heart history, was prescribed aspirin for decades by a brilliant, kind cardiologist. Maybe, the doctor thinking goes, this person is high risk-ish. Their dad died young, or they smoked, or don’t eat right, or have diabetes, or something else. So why not? It can’t hurt, and it might help.
Then, in 2018, three massive, high quality trials were published, showing when it just doesn’t matter, it matters.
Two studied people over 65 with risk factors like obesity and hypertension, and the third studied elderly diabetics. And in a rare confluence, all three (along with a fourth Japanese trial) found the same result: Aspirin for primary prevention was harmful. Indeed, in one study aspirin was a stone-cold killer, increasing deaths by a relative 14%.
So, um, it mattered.
All of this was tough news for Bayer who a few years earlier had asked the FDA to endorse aspirin for primary prevention, which the FDA promptly rejected. So, in a public foot-shot, Bayer helped fund one of the new studies. Bad call, Ripley.
There are myriad subtleties in these trials, but one cautionary tale highlights why so many are still prescribed daily aspirin for primary prevention. In the trial of diabetics there was sleight of hand. The researchers selected 'serious events'—heart attacks, strokes, and deaths—as their primary outcome of interest. Then midway through they added TIAs to the tally. TIAs are mini-strokes that typically resolve in minutes, and while they can lead to strokes, they overwhelmingly don’t. Calling all TIAs a serious event is like calling all chest pains a heart attack. But adding TIAs allowed them to ‘find’ a 1% advantage for aspirin.
It was clear there was no benefit without TIAs, and in truth bleeding problems eclipsed benefits regardless. But it just takes a glimmer to catch the eye of a true believer, and the medical mind has believed in aspirin for so long the researchers may have put their thumbs on the scale when they saw it failing.
Which suggests the real reason aspirin ever had life as a primary prevention drug: Earlier studies barely reported or downplayed aspirin’s harms, probably for the same reasons. Under-reporting harms and over-reporting benefits is rampant in research, particularly for well-loved or exciting and new treatments.
Therefore when studies appear to suggest a drug doesn’t matter, neither helping nor hurting, it matters. Even for wonder drugs (maybe especially) it’s wise to assume the benefits are smaller and the harms are bigger. You’ll virtually always be closer to the truth.