To take or not to take
New research is helping balance the risks and harms of aspirin.
Working out who should be prescribed aspirin to prevent heart attacks and stroke and who should not is the subject of a three-year, $600,000 research effort at the University of Auckland.
Public health physician Vanessa Selak is leading efforts to develop a risk-benefit chart that will enable doctors to readily measure when the adverse effects of aspirin – gastrointestinal or brain bleeds – outweigh its anti-clotting benefits.
People who’ve already had a heart attack or stroke are usually prescribed aspirin in conjunction with other drugs, including medicines to reduce blood pressure and cholesterol.
But the advice is less clear-cut for those who haven’t had a cardiovascular event but are nonetheless at high risk.
In New Zealand, aspirin isn’t generally recommended for people whose five-year risk of a heart attack or stroke is estimated at less than 20% – a much higher threshold than in the United States, where advice suggests it’s useful when the 10-year risk is as low as 10% (roughly equivalent to a five-year risk of 5%).
It’s a group for whom the balance of benefits and harms is most uncertain, says Selak. “The assumption that you should be starting a medication when your risk of a cardiovascular event is above a certain threshold is based on the assumption that the benefits will outweigh the harms – and that the harms stay about the same, irrespective of cardiovascular risk.
“But it’s more subtle and more complex than that.
Aspirin isn’t generally recommended for people whose five-year risk of a heart attack or stroke is estimated at less than 20% – a much higher threshold than in the US.
“It’s hard to make that statement without understanding what the risk of a bleed is, and that’s a fundamental piece of information that’s missing, because it underpins everything.”
The main risk factor for
an aspirin-related bleed is older age, but gender also comes into play, with men at higher risk than women. Diabetes, hypertension and smoking – all things that increase the risk of cardiovascular disease – also increase the risk of a bleed. The question is by how much.
“Balancing up the risks and harms is quite an art form,” says Selak. “What I’m trying to do is help doctors to unpack that in a more objective way.”
Selak’s Health Research Councilfunded work uses data gathered by Auckland professor of epidemiology Rod Jackson over the past 15 years from more than 500,000 New Zealand patients who’ve had cardiovascular risk assessments through their GPs. By tracking their outcomes, he has produced the Predict computer algorithm for New Zealand patients, which advises doctors about when to start treating patients and with what. It calculates an individual patient’s risk of heart attack or stroke based on factors including age, blood pressure, cholesterol level, smoking and diabetes.
Now Selak hopes her work, assessing the risk of treating with aspirin, will become an add-on to the Predict program. She says it could be available in general practice as early as the end of 2018.
In people aged 60-69 without diabetes and without a history of cardiovascular disease, the rates of major bleeds in those not on aspirin are 4.61 per 1000 person years in men and 3.45 in women. But if they receive aspirin, the expected rate of major bleeds rises to 7.10 in men and 5.31 in women.
The algorithms doctors currently use to guide patients on what treatment to have and when to start it – which are soon to be replaced by Jackson’s – were based on heart disease risk scores from patients in the long-running Framingham study in the US.
But Jackson has found those scores overestimate actual risk by nearly 100% when compared with the New Zealand cohort. That’s largely because the Framingham study started in 1948, but coronary death rates have been plummeting since the late 1960s.
Jackson says this negates the effect of the differences in the percentage thresholds being used in the US and
New Zealand to begin treatment.