An X-ray test commonly used to assess hardening of the arteries could help doctors decide whether the benefits of taking aspirin to prevent a first heart attack or stroke outweigh the risks of bleeding from its use, UT Southwestern research suggests.
The findings could give doctors and patients more concrete guidelines for making this important decision.
Due to its anti-clotting properties, aspirin is widely prescribed as a preventive measure to patients who have already had cardiovascular events, such as a heart attack or ischaemic stroke. However, aspirin’s role in primary prevention – averting first heart attacks and strokes – has been unclear, explains study leader Dr Amit Khera, professor of internal medicine.
After decades of commonly prescribing aspirin for primary prevention, recent guidelines from the American Heart Association (AHA) and American College of Cardiology (ACC)recommend more select use for those with the highest risk of cardiac events due to the increased risk of bleeding.
“We used to say for aspirin, generally yes, occasionally no,” Khera says. “With these new guidelines, we’ve flipped that on its head and are saying that we should not use aspirin for most people in primary prevention.”
However, he adds, it’s been unclear how to select which patients might still benefit most from aspirin therapy, taking into account the risk of bleeding. “We need tools to find that sweet spot where aspirin is most beneficial and offsets the associated risks,” he says.
In the study, Khera and his colleagues looked to a diagnostic test – coronary artery calcium (CAC) scanning – to see if it could help doctors make this important decision.
CAC scanning, a CT scan that scores the amount of calcium that lines the heart’s arteries, is commonly performed to detect hardening of the arteries and risk of a heart attack or stroke.
The researchers gathered data from the Dallas Heart Study, an ongoing study that tracks the development of cardiovascular disease in more than 6,000 adults in Dallas County. Initially, participants were invited to three visits for the collection of health and demographic information, laboratory samples, and various imaging studies, including CAC scanning. These volunteers were then followed for 12 years on average to track those who had heart attacks, died from heart disease, or had a nonfatal or fatal stroke – medical problems collectively called atherosclerotic cardiovascular disease – and/or who had a bleeding event that caused hospitalization or death.
The researchers used data from 2,191 participants with a mean age of 44 years who had CAC scans and follow-up information available. About 57% were female and 47% were Black.
Overall, about half of the participants had a CAC score of 0, suggesting little to no calcium build-up in their arteries. About 7% had a CAC score of more than 100, suggesting heavy calcium build-up. The rest had values in the middle (1-99).
When Khera and his colleagues examined the rates of atherosclerotic cardiovascular disease (ASCVD) and bleeding in the study group, they found that both events increased in a graded fashion as CAC scores rose. However, when they used statistical modelling to see how many of the ASCVD events may have been prevented by aspirin use – based on values gleaned from a recent meta-analysis that informed the AHA and ACC guidelines – they found that aspirin’s benefits only outweighed its risks for those with CAC scores above 100. For this group, the risk of ASCVD was about 15-fold and the bleeding risk about threefold of those with a CAC score of 0.
Yet, this effect only held true for those whose inherent risk for bleeding was already low, Khera says, meaning that in practice, as mentioned in the guidelines, if someone has had prior significant bleeding episodes, risk factors for bleeding, or was on medications that increase bleeding, they should not take aspirin for primary prevention regardless of their CAC score.
Together, Khera says, the findings reinforce new guidelines suggesting that aspirin for primary prevention is only appropriate for select patients and that CAC scanning can help doctors and patients make that decision.
“Aspirin use is not a one-size-fits-all therapy,” says Khera, who holds the Dallas Heart Ball chair in hypertension and heart disease. “CAC scanning can be a valuable tool to help us tailor care to help more patients avoid a first heart attack or stroke.”
This study was supported by grant UL1TR001105 from the National Centre for Advancing Translational Sciences, National Institutes of Health. Relevant financial interests of the authors are noted in the manuscript.
Importance: Higher coronary artery calcium (CAC) identifies individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk. Whether it can also identify individuals likely to derive net benefit from aspirin therapy is unclear.
Objective: To examine the association between CAC, bleeding, and ASCVD and explore the net estimated effect of aspirin at different CAC thresholds.
Design, Setting, and Participants: Prospective population-based cohort study of Dallas Heart Study participants, free from ASCVD and not taking aspirin at baseline. Data were analyzed between February 1, 2020, and July 15, 2020.
Exposures: Coronary artery calcium score in the following categories: 0, 1-99, and 100 or higher.
Main Outcomes and Measures: Major bleeding and ASCVD events were identified from International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes. Meta-analysis–derived aspirin effect estimates were applied to observed ASCVD and bleeding rates to model the net effect of aspirin at different CAC thresholds.
Results: A total of 2191 participants (mean [SD], age 44 [9.1] years, 1247 women [57%], and 1039 black individuals [47%]) had 116 major bleeding and 123 ASCVD events over a median follow-up of 12.2 years. Higher CAC categories (CAC 1-99 and ≥100 vs CAC 0) were associated with both ASCVD and bleeding events (hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; HR, 2.6; 95% CI, 1.5-4.3; HR, 4.8; 95% CI, 2.8-8.2; P < .001; HR, 5.3; 95% CI, 3.6-7.9; P < .001), but the association between CAC and bleeding was attenuated after multivariable adjustment. Applying meta-analysis estimates, irrespective of CAC, aspirin use was estimated to result in net harm in individuals at low (<5%) and intermediate (5%-20%) 10-year ASCVD risk and net benefit in those at high (≥20%) ASCVD risk. Among individuals at lower bleeding risk, a CAC score of at least 100 identified individuals who would experience net benefit, but only in those at borderline or higher (≥5%) 10-year ASCVD risk. In individuals at higher bleeding risk, there would be net harm from aspirin irrespective of CAC and ASCVD risk.
Conclusions and Relevance: Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. A high CAC score identifies individuals estimated to derive net benefit from primary prevention aspirin therapy from those who would not, but only in the setting of lower bleeding risk and estimated ASCVD risk that is not low.
Ezimamaka Ajufo, Colby R Ayers, Rebecca Vigen, Parag H Joshi, Anand Rohatgi, James A de Lemos, Amit Khera