“Heart patients who stop taking prescribed aspirin are two thirds more likely to suffer another attack,” the Daily Express has reported.
Taking low-dose aspirin each day is a standard treatment for preventing heart attacks in people who have a history of heart disease, but researchers estimate that around 50% of patients prescribed low-dose aspirin stop treatment. The research behind this news looked at how stopping was associated with the risk of another heart attack, as well as death related to heart disease.
Researchers compared the risks in patients who continued and recently stopped their prescriptions. They found that stopping aspirin use increased risk of a future non-fatal heart attack by 63%. For every 1,000 patients who stopped their aspirin use there were an additional four cases of non-fatal heart attacks over the course of a year compared with patients who continued their use of the drug.
Individuals on a low-dose aspirin treatment plan should not stop taking the drug without first consulting a doctor. They should discuss any concerns or side effects with their GP.
Where did the story come from?
The study was carried out by researchers from the Spanish Centre for Pharmacoepidemiologic Research, Gothenburg University in Sweden, and the Research and Development arm of AstraZeneca pharmaceutical company. It was also funded by AstraZeneca, which manufactures a blood-thinning drug often prescribed in conjunction with low-dose aspirin.
The study was published in the peer-reviewed British Medical Journal.
The findings of this study were reported accurately by BBC News. However, the Daily Express reported that the increased risk was related to seizures, which is inaccurate - the study did not look at seizures.
What kind of research was this?
This was a nested case-control study that used data from a long-running cohort study in the UK called The Health Improvement Network (THIN). The THIN database contains information on more than 3 million registered patients. The study aimed to determine how aspirin use was associated with the risk of heart attack and death from coronary heart disease in patients with a history of cardiovascular events such as heart attack or stroke. It compared the risk for people who stopped taking low-dose aspirin against the risk for people who continued taking the drug.
A case-control study is a useful way to compare characteristics of people who have a certain disease or who have experienced a health event (such as a heart attack) with those who have not experienced the disease or event. Studies of this type allow researchers to determine what characteristics are associated with an increased risk for the disease.
What did the research involve?
Researchers identified individuals in the THIN database aged between 50 and 84 with a history of cardiovascular events (such as heart attack, stroke or angina) who had been prescribed low-dose aspirin (75-300mg daily) for the prevention of further cardiovascular events. Researchers looked at records between the years 2000-2007, and identified approximately 40,000 individuals who fitted these criteria. They then identified which of these 40,000 eligible individuals went on to be admitted to hospital for a non-fatal heart attack or who had died from coronary heart disease. These individuals who died or had a heart attack were considered to be the ‘cases’.
Researchers then formed their ‘control group’ by randomly selecting 5,000 individuals from the remaining members of the eligible patient population. They matched these individuals to the cases on the basis of age, sex and calendar year of health event. For example, if an identified case was a 65-year-old female who had a non-fatal heart attack in 2005, as a control they selected a female who did not have a non-fatal heart attack and was 65 years old in 2005.
Researchers next assessed both cases and controls for factors that might be related to risk of a heart attack or death from coronary heart disease. The main factor they were interested in was low-dose aspirin discontinuation, which was identified by looking for people who had not renewed their prescription for aspirin within 30 days of the date when their last low-dose aspirin prescription would have run out.
Individuals whose prescriptions would have run out in the past 30-180 days were classified as recent discontinuers. Based on reviewing the patients’ records, the reason for discontinuation was classified as a change to a different type of treatment, safety concerns, a switch to over-the-counter aspirin instead of prescribed aspirin, or a lack of adherence (compliance with) their prescription – this last category included anyone for whom another reason for discontinuation could not be identified.
The other factors examined included:
- number of GP visits
- number of referrals to a specialist
- number of hospital admissions
- lifestyle factors, including smoking and obesity
- diagnosed diseases, including ischaemic heart disease, cerebrovascular disease, diabetes and chronic obstructive pulmonary disease (COPD)
- drug treatment other than low-dose aspirin, including other forms of blood-thinning medication, statins, nitrates, medication for high blood pressure, oral steroids or non-steroidal anti-inflammatory drugs.
What were the basic results?
The study identified 876 non-fatal heart attacks and 346 deaths from coronary heart disease in the group of 40,000 eligible patients. The overall rate of non-fatal heart attacks was 6.87 per 1,000 person years (that is, if 1,000 people were followed for one year, about seven people would be expected to have a non-fatal heart attack). The overall rate of death from coronary heart disease was 2.71 per 1,000 person years.
Researchers found that the risk of having a non-fatal heart attack increased by 63% in patients who had recently stopped taking their low-dose aspirin prescription, compared to patients who continued taking the drug (Odds Ratio [OR] 1.63, 95% Confidence Interval [CI] 1.23 to 2.14). This meant that over the course of a year there would be four more cases of non-fatal heart attack per 1,000 patients who had recently stopped taking their low-dose aspirin than there would be among 1,000 patients who continued taking the drug. Patients who had stopped taking their low-dose aspirin prescription were at no greater risk of death from coronary heart disease than patients who continued taking the drug (OR 1.07, 95% CI 0.67 to 1.69).
When researchers analysed the data according to reason for discontinuation (a change to a different type of treatment, safety concerns or a switch to over-the-counter aspirin instead of prescribed aspirin), they found:
- an 80% increased risk of having a non-fatal heart attack in those who stopped taking low-dose aspirin due to lack of adherence, compared to those who continued taking the drug (OR 1.80, 95% CI 1.31 to 2.48)
- a 119% increased risk of having a non-fatal heart attack in those who stopped taking low-dose aspirin due to a treatment change, compared to those who continued taking the drug (OR 2.19, 95% CI 1.04 to 4.60)
- no significant change in risk of having a non-fatal heart attack in those who stopped taking low-dose aspirin due to safety concerns, compared to those who continued taking the drug (OR 0.93, 95% CI 0.42 to 2.05)
- no significant change in risk of having a non-fatal heart attack in those who stopped taking low-dose aspirin due to switching to over-the-counter aspirin, compared to those who continued taking the drug (OR 0.86, 95% CI 0.25 to 2.89)
How did the researchers interpret the results?
Researchers concluded that patients with a history of cardiovascular events who stop taking low-dose aspirin are at an increased risk of future non-fatal heart attack compared to those who continue their aspirin regimen.
This was a well-designed nested case-control study, which found an association between discontinuation of daily low-dose aspirin and risk of future non-fatal heart attack in people with a history of cardiovascular disease. There are some points to note:
- The use of a well-established database of UK general practice data increases the likelihood that these results are representative of the risk in the UK.
- As with all databases, there may be some level of inaccuracy in the data or missing information. For example, reason for aspirin discontinuation may not have been recorded in all cases.
- Classification of aspirin use was based on prescription records. These records may not fully reflect a patient’s aspirin use – patients might not always take aspirin in the way their prescription directs them, or they might miss doses.
- The data analysis by reason for discontinuation resulted in larger effects seen in certain subgroups. When a body of data is broken down in this way, it reduces the number of individuals in each group. Therefore these results need to interpreted with more caution than the overall results.
- Individuals stopping aspirin may differ in other ways from those who continue to take aspirin, and this could influence the differences seen. The researchers appropriately took a number of factors that could be influencing results into account, but other unknown or unmeasured factors may be having an effect.
As with any drug, aspirin does have side effects, including gastrointestinal problems. Individuals on a low-dose aspirin treatment plan should discuss any concerns or side effects with their GP. They should not stop taking the drug without first consulting a physician.