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Aspirin in the balance

MagazineFebruary 2014 (Vol. 24 Issue 11)Aspirin in the balance

Many of us take an aspirin a day as a 'just-in-case'remedy

Many of us take an aspirin a day as a 'just-in-case' remedy. New evidence suggests that the risks could be outweighing any benefits, and people need to think twice

Even people who think twice about taking a pharmaceutical don't give a moment's thought to popping an aspirin every morning. After all, it's the ultimate 'just-in-case' lifestyle pill, offering protection against heart disease and colorectal (bowel) cancer; doctors regularly recommend it as part of the general health regimes to all their patients who are 50-plus.

But a major new analysis of the risks and benefits of routine aspirin use paints a worrying picture: it could be costing as many lives as it saves.

"There is an incredibly fine balance between the possible benefits and risks
of the intervention," points out Prof Aileen Clarke, who led the team of investigators at Warwick Medical School in Coventry, UK.1

The benefits of taking aspirin are certainly real, but possibly far less impressive than doctors would have us believe. Taking an aspirin every day for 10 years can reduce the rate of major cardiovascular events like heart attacks by around 10 per cent, and coronary heart disease by 15 per cent, the Warwick researchers have discovered. That translates into 33 to 46 fewer deaths for every 100,000 people who take an aspirin every day for 10 years.

The same picture emerged for lives saved from colon cancer: after taking aspirin every day for five years, there were 34 fewer deaths per 100,000 people.

Any life saved has to be worth it, but compare that to the estimated 130,000 lives that might be saved every year from all cancers if every adult in the US took a multivitamin supplement every day.2

And the real problem is that aspirin giveth-but it taketh away just as readily. In assessing 27 large randomized trials, the Warwick researchers discovered the drug increases the rate of gastrointestinal (GI) bleeding by 37 per cent and the risk of stroke by 38 per cent. Translate that into numbers, and it means there are 117 extra cases of GI bleeding per 100,000 people taking aspirin and up to 10 additional cases of stroke, which is debilitating at best and fatal at worst.

Who's there?

The real picture could be even grimmer. It's been known for years that aspirin causes GI bleeding, but the extent and severity of the problem has remained something of a mystery. This may well be down to aspirin's positive image as a safe, everyday medication that we can all take with no worries.

This positive image means aspirin often slips under the radar, just like the murderer whom nobody suspects in a TV crime thriller. Researchers from the Eastern Virginia Medical School made just this discovery when they carried out a series of interviews with patients at a hospital specializing in GI problems. Only one in five patients had even bothered reporting the fact they were taking aspirin, as they didn't consider it to be of any consequence.

When the researchers put aspirin back into the picture, they discovered it could be killing around 20,000 Americans every year from GI complications-yet none of the deaths has ever been attributed to the drug.3

Extrapolating the figures worldwide, it could be that aspirin is responsible for around 100,000 deaths and 500,000 emergency hospital treatments each year, and yet it has never been implicated in any of them.

If the deaths and injuries haven't been attributed to aspirin and so haven't been picked up by the Warwick team, this suggests that the risks/rewards balance has now actually become heavily weighted on the risks side, so outweighing the benefits.

Not for the elderly

There's another element to the equation you have to consider before deciding whether to start taking aspirin daily: your age. As the risk of GI bleeding starts from the first day you take aspirin, but any health benefits start to kick in only after five to 10 years of daily use, starting late in life may be the same as not starting at all.

Anyone 75 years or older shouldn't start a daily aspirin regime as a lifestyle choice, suggests Prof Peter Rothwell at Oxford University. Not only will elderly persons not get any real benefit from aspirin, they will also be far more susceptible to GI bleeding.

Rothwell found a sevenfold increase in intracerebral haemorrhagic stroke (bleeding in the brain) among the over-75s.4 Although he has been unable to prove that aspirin is the cause, the rise does correlate with the increasing use of an NSAID (non-steroidal anti-inflammatory drug), which includes aspirin, in that age group to help thin the blood. Between 1981 and 1984, just 4 per cent of healthy individuals were taking aspirin or other NSAIDs as a just-in-case remedy; by 2006, this had risen to 40 per cent of the population.

Coincidence? Possibly, but Rothwell doesn't believe it's worth taking the risk. "There are elderly people who take aspirin as a lifestyle choice, and, in that situation, the trials have shown there's no benefit. And what our study suggests is that, particularly in the very elderly, the risks of aspirin outweigh the benefits."4

There's also a massaging of the figures that is, at best, suspicious. Deaths from stroke have fallen significantly in the UK over the past 20 years, and doctors have been quick to champion aspirin as the reason for this victory. But, strangely, the statistics have always omitted the over-75s, the people most at risk from stroke and the group that has also seen a massive increase in stroke death, as Rothwell's own analysis discovered.

Not such a hero

Aspirin's cancer-fighting abilities may also be a little overblown. It's an idea that has been gaining potency since the 1990s, when it was first noted by doctors that people taking aspirin didn't seem to develop cancer. Researchers theorized that aspirin and other NSAIDs contained a chemical agent that blocked an enzyme that turned healthy cells into cancerous ones.

Their conjectures seemed to be confirmed by the major long-term Nurses' Health Study, which noted that those who regularly took aspirin were less likely to develop cancer; essentially, those who took between four and six aspirin tablets a week halved their risk of colorectal (colon) cancer, although the protective effect only became apparent after taking the drug for 10 years, and the benefit was delayed by a further 10 years in those taking fewer aspirins per week.5

Strangely, the Nurses' Health Study was the only one ever to discover any cancer-fighting qualities. A study of 22,000 doctors a few years later could find no protective effects, and neither did one involving nearly 40,000 women given either 100 mg of aspirin or a sugar pill (placebo) every other day for 10 years. At the end of that study, the number of cases of cancer was similar in both groups.6

So where did the cancer protection go? The good news is that it's still there, but it only seems to benefit a tiny fraction of the population.

One research team found that aspirin can protect against bowel cancer, but only in cases of a hereditary disposition known as Lynch syndrome.7 To put that in perspective, just 5,000 people in the UK have the syndrome; great news of course, but not exactly the massive breakthrough the study sponsors, Bayer Pharma and Bayer Corporation, may have been looking for. Bayer, by the way, manufactures Aspirin.

All of which pushes the balance between risk and benefit even further towards risk. What the Warwick researchers described as delicate may, in fact, be overwhelming.

Some data

> Until 1971, no one knew how aspirin worked. It took John Vale, a British pharmacologist, to work out that aspirin suppresses the production of prostaglandins and thromboxanes (hormone-like lipids) that regulate many physiological functions.

> People around the world swallow around 100 billion aspirin tablets a year, and that's increasing by around 15 per cent a year

>Aspirin's principal active ingredient, salicylic acid, was first discovered by Hippocrates, the ancient Greek physician recognized as the father of medicine, in the 5th century BC. Derived from the bark of the willow tree and the meadowsweet herb, it helps relieve pain and is antipyretic (it reduces fever)

> Aspirin was the very first drug in the family of NSAIDs (non-steroidal anti-inflammatory drugs) when Bayer, a German pharmaceutical company, began marketing it in 1899 along with one of the company's other discoveries: heroin

> Aspirin with a capital 'A' remains a protected brand owned by its original manufacturer, Bayer. As 'aspirin', it's not trademark protected, and is used in more than 50 over-the-counterpreparations either as aspirin or SA, an abbreviation of acetylsalicylic acid, Aspirin's generic name

Bryan Hubbard

References

1

Health Technol Assess, 2013; 17: 1-253

2

Nutrients, 2013; 5: 5161-92

3

Gastroenterology Insights, 2013; 5: e3

4

Lancet Neurol, 2007; 6: 487-93

5

N Engl J Med, 1995; 333: 609-14

6

JAMA, 2005; 294: 47-55

7

Lancet, 2011; 378: 2081-7


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