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Should you be taking aspirin?

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A daily aspirin tablet can lower the risks of many diseases – including colorectal and breast cancer – but your age is critical to avoid bleeding in the brain. 

When he turned 55, Professor Harvey White started taking a daily dose of aspirin to lower his risk of stroke, heart attack and bowel cancer. White is one of our most prominent cardiologists, so if he’s popping a pill in middle age as a precaution, then you’d assume the rest of us should follow suit.

After all, our rates of bowel cancer are among the highest in the world, stroke is our third-largest killer and a major cause of disability, and our heart disease rate is above the OECD average. Plus the blood-thinning benefits of aspirin may extend to preventing or slowing the spread of other cancers and potentially staving off diseases of the elderly, such as macular degeneration and dementia.

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So what’s not to like? Unfortunately, quite a lot. After numerous studies, aspirin remains as controversial as it is simple and cheap.

The drug has been available as a painkilling medication for more than 100 years, but medicinal use of its active ingredient salicin, made from willow bark, stretches back into antiquity. In the 1970s, studies began to show it could prevent a further heart attack or stroke in people who had already had one. Then, in the 1980s, the Physicians’ Health Study, a large trial involving male doctors over the age of 40, was halted several years early because the benefits seemed so obvious. It found that aspirin decreased the risk of a first heart attack by 44%.

After that, low-dose aspirin became an important tool in primary prevention, and today one in five American adults takes it daily to prevent their blood cells clumping together to form a clot. White says we don’t have any data for the number of New Zealanders taking aspirin, but he reckons it’s about half the US rate.

The trouble is blood-thinning drugs carry a risk of bleeding. So yes, they reduce the chance of clots, but they increase the chance of a stroke caused by bleeding in the brain. And since aspirin can erode the stomach lining, there is more chance of bleeding in the gut as well.

The elderly have the most to gain and also the most to lose. The older you are, the higher your risk of a stroke or heart attack but also the higher the risk of a serious bleed. In fact, a recent study from the University of Oxford suggests that daily low-dose aspirin may be causing more than 3000 deaths a year in the UK and found those over the age of 75 were 10 times as likely to suffer a bleed as those not taking the drug.

Professor Harvey White. Photo/Ken Downie

A numbers game

White, director of coronary care and cardiovascular research at Auckland City Hospital, remains convinced that swallowing a daily 75-100mg of the drug is a sensible idea. For him, it’s a numbers game. He has looked at the available evidence and seen that for a man or woman in his age group, there is still considerably more chance of benefits than there is of a bleed.

“If you’re 50 to 59, you should take low-dose aspirin as a preventative,” he says. “If you’re younger, then there is less benefit as your stroke risk is lower. And if you’re older, there is more chance of bleeding. So it’s a continuum of balancing the risks.”

White refers to guidelines released last year by the US Preventive Services Task Force following a review of numerous studies. These say that if you’re healthy, without any of the risk factors for bleeding – smoking, high blood pressure, previous bleeding and diabetes – and you’re under 70, then the benefits of daily low-dose aspirin can outweigh the harms, and the recommendation is to consider taking it if you have a 10% or greater risk of cardiovascular disease or colorectal cancer.

For women, there seems to be a particularly strong stroke benefit. And to gain significant cancer prevention, people need to take aspirin for five to 10 years, so ideally they will begin between the age of 50 and 59.

Once you’re over 70, it becomes more difficult to determine whether the protective effects are outweighed by the potential for harm. “We were operating in the dark giving aspirin to older people,” says Professor John McNeil, head of Monash University’s Department of Epidemiology and Preventive Medicine in Melbourne. “There was no evidence around to tell us whether aspirin was good for primary prevention in the over seventies. It became obvious we needed a clinical trial to see whether we should be prescribing it.”

That trial is called Aspree (Aspirin in Reducing Events in the Elderly), the largest primary prevention study ever undertaken in healthy older people. Its scope extends far beyond aspirin’s effect on the risk of cardiovascular events, with sub-studies looking at whether its anti-inflammatory action could stave off depression, hearing loss, bone fragility and severe infection in older people, and whether it might help in the early stages of age-related macular degeneration and slow down cognitive decline.

Aspirin can help protect against, from left, a heart attack and bowel cancer, but increases the risk of a stroke caused by bleeding in the brain. Photo/Getty Images

Eventually, there were 19,000 people aged 70 or more, mostly from Australia and the rest from the US, taking a daily 100mg aspirin or a placebo and being measured in various ways.

Then in June, the funding body, the US National Institute on Aging, which had been monitoring the data being collected, pulled the plug on the intervention side of the study. The Aspree participants were advised to wean themselves off their medication earlier than intended, not due to new evidence of bleeding risk but because aspirin wasn’t showing any clear benefits for the study’s main aim: to extend disability-free survival.

“It’s disappointing, but the question had to be answered one way or another, because a hell of a lot of people are taking aspirin,” says McNeil, one of the lead Aspree investigators. “And we’re still collecting and analysing the data. We might see big benefits for some people and risks for others.”

The results are due to be published in 2018, but the cancer angle will require participants to be followed for several more years. In the meantime, there isn’t enough data from Aspree to present a compelling case for the healthy elderly taking aspirin as a preventative.

For others, some persuasive evidence is out there. A 2015 study at Leiden University in the Netherlands found that patients with gastrointestinal tumours who took aspirin as part of their cancer treatment doubled their chances of survival. One theory puts this down to aspirin’s antiplatelet effect: platelets, which try to stop bleeding, tend to clump around tumour cells, making it harder for the immune system to recognise them and prevent them from spreading, but aspirin inhibits this, allowing the immune system to detect the cells and eliminate them.

The strongest connection is for colorectal cancer – studies have shown it lowers the risk of dying from it by about 30% for men and women. New research using data from the California Teachers Study has shown that regular use of low-dose aspirin also reduces the risk of breast cancer in women by 16%. This may be down to its anti-inflammatory action; but it is also a mild aromatase inhibitor, reducing the amount of oestrogen in the body.

Another large clinical trial called Add-Aspirin is being done in the UK and India to find out whether taking daily aspirin for five years after treatment for a variety of early-stage cancers can stop the disease or delay its return. So aspirin may still turn out to be a cancer hero.

Professor John McNeil.

Aspirin and strokes

It has been established that if you’ve already had a heart attack or stroke, then taking aspirin will substantially reduce the risk of suffering a second one and it is commonly prescribed. There is also an argument for taking the drug if your risk of a stroke is high.

However, when he had a series of strokes while mid-air on a flight from Sydney to Wellington, Mark Corbitt was very much low risk. He was 50, didn’t smoke or have high blood pressure and had an only slightly elevated cholesterol level.

“It pretty much came out of the blue,” he says. “Two months earlier, I’d done a 100km bike race and I was having a complete medical every two years. So I considered myself very fit and healthy.”

Corbitt had blacked out a couple of weeks earlier, but he’d put that down to tiredness as he’d been working hard in his then role as chief information officer for Contact Energy. Then on the plane, when he lost control of one side of his body and his speech became slurred, he realised what was happening and alerted the flight attendant. Half an hour later, he had a bigger stroke. “That one locked me into my seat for the remainder of the flight.”

In Wellington Hospital, the strokes kept coming, and after having a CT scan, Corbitt learnt he had a blocked artery in his brain stem. Fortunately, his treatment was successful, and two years later, he’s back to full health. He takes a combination of statins and aspirin to prevent the same thing happening again, but his neurologist told him that to maximise his chances of staying stroke-free, he also needed to revamp his diet.

“I ate a lot of meat and dairy,” admits Corbitt. “It was a standing joke in the family that if they cooked a vegetarian meal, they’d have to do a sausage for me. I haven’t had any since I left hospital. Now I eat a plant-based wholefood diet plus some fish.”

It took him three months to adjust to the change. “But if someone throws you a lifeline, you don’t question whether you should take it.”

Family, friends and workmates were all affected by his experience, because they had considered him to be the healthy one. “Suddenly no one was touching the chocolate afghans in meetings any more.”

Now Dunedin-based, Corbitt isn’t tempted to go back to his old high-fat diet, even though at times it can be difficult to find healthy food.

“I want to stay mobile to my late seventies like my parents. While you can’t live in fear, you have to do what you can. Unfortunately, a lot of people don’t want to change. They’d rather pop a pill.”

Professor Valery Feigin. Photo/Tony Nyberg

Lifestyle vs drugs

Auckland’s Professor Valery Feigin would agree with him. The director of AUT’s National Institute for Stroke and Applied Neurosciences is passionate about prevention and believes the emphasis should be on lifestyle rather than drugs.

“Lifestyle risk factors are responsible for three-quarters of the burden of stroke,” he says.

“And in New Zealand the prevalence of risk factors is very high: obesity, high blood pressure, our smoking, which is still high in comparison with Australia, and our blood-glucose levels, which are the highest in the world – that’s a shocking fact. We all know it causes diabetes, which is related to stroke and cardiovascular disease.”

The New Zealand health system is already struggling to adequately rehabilitate stroke survivors. Feigin believes that as our population ages and the number of survivors increases, this will threaten the sustainability of the system. And, he points out, we are seeing increasing incidences of stroke in young people.

By now, everybody knows the key to better health is to be active, eat well and avoid smoking. We’ve all been well educated in how it reduces our chances of developing a range of non-communicable diseases, including stroke, heart attack and cancer. But how many of us are following the recommendations?

“The key is motivation,” says Feigin. “And that involves telling people the truth about their individual risk. The best way to do this is mobile technology. It’s so widely used it would be stupid not to use this opportunity to provide health information.”

Feigin’s belief is that it’s not only your absolute risk you need to be aware of but your risk in comparison with healthy people your age. To that end, AUT has developed a free app, Stroke Riskometer, which to date has had more than 100,000 downloads worldwide and comes up in the No 1 spot if you search for stroke in the Apple App Store.

It takes a few minutes, covers 18 risk factors, including gender, ethnicity, family history, fruit and vegetable consumption, traumatic brain injury and medical history.

And Feigin is right. Learning that my absolute risk is 0.72% didn’t worry me, but discovering that this is twice what’s normal for my age prompted me to use the app to look further into what I’m doing wrong.

AUT has studied a group in South Auckland using the app and found it helped a significant number of them to make behavioural changes. It’s self-management,” says Feigin, “although ideally it would be combined with a doctor’s advice, because the app is not perfectly individualised.”

He is pleased that in the latest International Classification of Diseases, stroke has been listed under neurological disorders rather than cardiovascular. He was part of the World Health Organization group that advised on that change and sees it as a major shift that will have positive results both for stroke services and research.

“Stroke research has lagged so far behind. Previously, it was not a priority. Now it’s in its proper place, hopefully it will attract more funding.”

In the meantime, a daily low-dose aspirin may be worth considering for primary prevention if you’re under 70.

For those who are older, heartburn drugs known as proton-pump inhibitors can be prescribed to lower the chance of a bleed, although these carry their own side effects and hazards.

In Feigin’s opinion, medication shouldn’t be our first or only line of defence. “Aspirin is not improving your lifestyle. It’s not a magic pill.”

Gut feeling about aspirin

Some of the effects of aspirin may result from changes to the gut microbiome. Gut microbes reflect what we eat, and that includes over-the-counter aspirin.

Studies have shown it’s possible to identify regular aspirin users from the levels of certain bacteria in their gut. Aspirin users have more of four particular species, but scientists don’t yet know whether the changes reflect the use of aspirin or the underlying condition the aspirin is being used to treat.

In the US, a University of Minnesota study is investigating whether aspirin reduces the risk of bowel cancer by targeting the gut microbiome.

The clinical trial, due to be completed in August, is examining the correlation between aspirin-related changes to the microbiome and levels of inflammatory biomarkers in blood and urine.

This article was first published in the August 12, 2017 issue of the New Zealand Listener.