Houston, Texas, USA : The jury is still out on whether people at moderate risk of a first heart attack or stroke should take daily aspirin to lower their risk, according to late breaking results from the ARRIVE study presented today in a Hot Line Session at ESC Congress 2018 and with simultaneous publication in the Lancet.
Taking a low-dose aspirin every day has long been known to cut the chances of another heart attack, stroke or other heart problem in people who already have had one, but the risks don’t outweigh the benefits for most other folks, major new research finds.
Although it’s been used for more than a century, aspirin’s value in many situations is still unclear. The latest studies are some of the largest and longest to test this pennies-a-day blood thinner in people who don’t yet have heart disease or a blood vessel-related problem.
One found that aspirin did not help prevent first strokes or heart attacks in people at moderate risk for one because they had several health threats such as smoking, high blood pressure or high cholesterol.
Another tested aspirin in people with diabetes, who are more likely to develop or die from heart problems, and found that the modest benefit it gave was offset by a greater risk of serious bleeding.
Aspirin did not help prevent cancer as had been hoped.
And fish oil supplements, also tested in the study of people with diabetes, failed to help.
“There’s been a lot of uncertainty among doctors around the world about prescribing aspirin” beyond those for whom it’s now recommended, said one study leader, Dr. Jane Armitage of the University of Oxford in England. “If you’re healthy, it’s probably not worth taking it.”
Professor J. Michael Gaziano, principal investigator, of the Brigham and Women’s Hospital, Boston, US, said: “Aspirin did not reduce the occurrence of major cardiovascular events in this study. However, there were fewer events than expected, suggesting that this was in fact a low risk population. This may have been because some participants were taking medications to lower blood pressure and lipids, which protected them from disease.”
The benefit of aspirin for preventing second events in patients with a previous heart attack or stroke is well established. Its use for preventing first events is controversial, with conflicting results in previous studies and recommendations for and against its use in international guidelines. Recommendations against its use cite the increased risk of major bleeding.
The ARRIVE study assessed the impact of daily aspirin on heart attacks, strokes, and bleeding in a population at moderate risk of a first cardiovascular event. Moderate risk was defined as a 20-30% risk of a cardiovascular event in ten years. The study enrolled individuals with no prior history of a vascular event, such as stroke or heart attack. Men were at least 55 years old and had two to four cardiovascular risk factors, while women were at least 60 years old with three or more risk factors. Risk factors included smoking, elevated lipids, and high blood pressure.
A total of 12,546 participants were enrolled from primary care settings in the UK, Poland, Germany, Italy, Ireland, Spain, and the US. Participants were randomly allocated to receive a 100 mg enteric-coated aspirin tablet daily or placebo. The median follow-up was 60 months. The primary endpoint was time to first occurrence of a composite of cardiovascular death, myocardial infarction, unstable angina, stroke, and transient ischaemic attack.
The average age of participants was 63.9 years and 29.7% were female. In the intention-to-treat analysis, which examines events according to the allocated treatment, the primary endpoint occurred in 269 (4.29%) individuals in the aspirin group versus 281 (4.48%) in the placebo group (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.81-1.13, p=0.60). In the per-protocol analysis, which assesses events only in a compliant subset of the study population, the primary endpoint occurred in 129 (3.40%) participants of the aspirin group versus 164 (4.19%) in the placebo group (HR 0.81, 95% CI 0.64-1.02, p=0.0756).
In the per-protocol analysis, aspirin reduced the risk of total and nonfatal myocardial infarction (HR 0.53, 95% CI 0.36-0.79, p=0.0014; HR 0.55, 95% CI 0.36-0.84, p=0.0056, respectively). The relative risk reduction of myocardial infarction in the aspirin group was 82.1%, and 54.3% in the 50-59 and 59-69 age groups, respectively.
All safety analyses were conducted according to intention-to-treat. Gastrointestinal bleedings, which were mostly mild, occurred in 61 (0.97%) individuals in the aspirin group versus 29 (0.46%) in the placebo group (HR 2.11, 95% CI 1.36-3.28, p=0.0007). The overall incidence of adverse events was similar between treatment groups. Drug-related adverse events were more frequent in the aspirin (16.75%) compared to placebo (13.54%) group (p<0.0001), the most common being indigestion, nosebleeds, gastro-oesophageal reflux disease, and upper abdominal pain.
Professor Gaziano said: “Participants who took aspirin tended to have fewer heart attacks, particularly those aged 50-59 years, but there was no effect on stroke. As expected, rates of gastrointestinal bleeding and some other minor bleedings were higher in the aspirin group, but there was no difference in fatal bleeding events between groups.”
He concluded: “The decision on whether to use aspirin for protection against cardiovascular disease should be made in consultation with a doctor, considering all the potential risks and benefits.”
Sources of funding: Bayer.
Disclosures: R Coppolecchia is an employee of bayer healthcare. All other members of the executive committee are consultants to bayer and received person fees.
Aspirin For People With Diabetes?
People with diabetes have a higher risk of heart problems and strokes from a blood clot, but also a higher risk of bleeding. Guidelines vary on which of them should consider aspirin.
Oxford researchers randomly assigned 15,480 adults with Type 1 or 2 diabetes but otherwise in good health and with no history of heart problems to take either aspirin, 1 gram of fish oil, both substances, or dummy pills every day.
After seven and a half years, there were fewer heart problems among aspirin users but more cases of serious bleeding, so they largely traded one risk for another.
Fish oils do not prevent heart attack or strokes in people with diabetes
Fish oil supplements do not prevent heart attacks or strokes in patients with diabetes, according to late breaking results from the ASCEND trial presented today in a Hot Line Session at ESC Congress 20181 and published in the New England Journal of Medicine.
In observational studies, higher consumption of fish is associated with lower risks of coronary artery disease and stroke. However, previous randomised trials have not been able to show that taking fish oil supplements containing omega-3 fatty acids reduce the risk of having cardiovascular events.
The ASCEND trial (A Study of Cardiovascular Events iN Diabetes)2 examined whether fish oil supplements reduce the risk of a cardiovascular event in patients with diabetes. Between 2005 and 2011, 15,480 patients with diabetes but no history of cardiovascular disease were randomly assigned to fish oil supplementation (1 g daily) or matching placebo.
The primary efficacy outcome was first serious vascular event, which included non-fatal heart attacks, non-fatal strokes or transient ischaemic attacks (sometimes called “mini-strokes”), or deaths from a cardiovascular cause (but excluding any intracranial haemorrhage; i.e. bleeding in the head or brain3).
During an average of 7.4 years of follow-up, a first serious vascular event occurred in 689 (8.9%) participants allocated fish oil supplements and 712 (9.2%) participants allocated placebo. There was no significant difference between the two groups: rate ratio of 0.97 (95% confidence interval 0.87-1.08, p=0.55).
Dr Louise Bowman, principal investigator, Nuffield Department of Population Health, University of Oxford, UK, said: “Our large, long-term randomised trial shows that fish oil supplements do not reduce the risk of cardiovascular events in patients with diabetes. This is a disappointing finding, but it is in line with previous randomised trials in other types of patient at increased risk of cardiovascular events which also showed no benefit of fish oil supplements. There is no justification for recommending fish oil supplements to protect against cardiovascular events.”
“We feel very confident that there doesn’t seem to be a role for fish oil supplements for preventing heart disease,” said study leader Dr. Louise Bowman of the University of Oxford.
The British Heart Foundation was the study’s main sponsor. Bayer and Mylan provided aspirin and fish oil, respectively. Results were published by the New England Journal of Medicine.
The study was designed and run independently of the funders by the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) in the Nuffield Department of Population Health (NDPH). The lead investigators abide by the CTSU guidelines not to accept payment or honoraria from drug companies.
Other studies are testing different amounts and prescription versions of fish oil, “but I can’t tell people go spend your money on it; we think it’s probably better to eat fish,” said Dr. Holly Andersen, a heart disease prevention specialist at New York-Presbyterian/Weill Cornell who was not involved in the study.
The new research doesn’t alter guidelines on aspirin or fish oil, said Dr. Nieca Goldberg, a cardiologist at NYU Langone Medical Center and an American Heart Association spokeswoman. They recommend fish oil only for certain heart failure patients and say it’s reasonable to consider for people who have already suffered a heart attack.
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