in a new analysis from the large randomized ASPREE trial released as part of the annual Digestive Disease Week.
The analysis identified several independent risk factors for major GI bleeding – advanced age, hypertension, obesity, smoking, and chronic kidney disease – according to Suzanne E. Mahady, MBBS, PhD, a gastroenterologist and clinical epidemiologist at Monash University in Melbourne.
“To date, there [are] no comparable data assessing aspirin-related bleeding in older healthy people from a large randomized, controlled trial. Previous data [have] been observational, with variable definitions of significant bleeding, and retrospective. We derived a standard definition for bleeding, used physicians to adjudicate bleeding endpoints, and followed older people for 5 years,” she explained in an interview.
“Our data on bleeding [are] novel,” Dr. Mahady added. “It will help clinicians assess who is most at risk of bleeding with aspirin and target modifiable bleeding risk factors where possible.”
ASPREE was a double-blind trial including 19,114 apparently healthy Australian and American adults age 70 or older, or age 65-plus for blacks and Hispanics in the United States. Participants were randomized to 100 mg/day of enteric-coated aspirin or placebo. At a median 4.7 years of follow-up, there was no between-group difference in major adverse cardiovascular events, a lack of benefit accompanied by a 38% greater risk of major hemorrhage risk and a statistically significant 14% increase in all-cause mortality in the aspirin group. (N Engl J Med. 2018 Oct 18;379:1509-18). The chief contributor to the excess mortality in the aspirin group was their 31% greater risk of cancer-related death (N Engl J Med. 2018 Oct 18;379:1519-28).
The new analysis of severe GI bleeding documented an absolute 5-year risk of 0.2% for 70-year-olds and 0.4% in 80-year-olds on aspirin. In 80-year-olds with additional GI bleeding risk factors as identified in the study, the rate reached up to 5.5%. The risk of major upper GI bleeding events was 87% greater in the aspirin group, compared with placebo-treated controls, and the risk of serious lower GI bleeding was increased 36%.
ASPREE coinvestigator Andrew T. Chan, MD, said that the bleeding data should prove useful in future efforts to appropriately weight the risks and benefits of low-dose aspirin treatment.
“We need to better understand how to incorporate bleeding risk in clinical decision making about how to use aspirin among older adults because aspirin has many potential benefits, including prevention of colorectal cancer,” said Dr. Chan, a gastroenterologist and professor of medicine at Harvard Medical School and director for cancer epidemiology at Massachusetts General Hospital, both in Boston.
However, ASPREE has soured cardiologists on the decades-long practice of recommending aspirin for primary prevention of cardiovascular disease in older individuals. In response to the publication of primary outcomes in ASPREE, which was closely bracketed by publication of the largely negative results of the randomized ARRIVE and ASCEND trials in a collective 47,000-plus randomized patients, the American College of Cardiology/American Heart Association clipped aspirin’s role for primary prevention of atherosclerotic cardiovascular disease. The current recommendation is that low-dose aspirin should not be administered on a routine basis for primary cardiovascular prevention in people above age 70, nor in adults at any age at increased bleeding risk, although the practice “might be considered” for primary prevention in select higher atherosclerotic cardiovascular disease–risk 40- to 70-year-olds, provided they are not at increased bleeding risk (J Am Coll Cardiol. 2019 Sep. doi: 10.1016/j.jacc.2019.03.010).
Dr. Mahady reported having no financial conflicts of interest. Dr. Chan serves as a consultant to Bayer Pharma, Janssen, and Pfizer.