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While there is clear evidence that aspirin use provides protection against secondary cardiovascular events in those at high risk, its role in primary prevention is more complicated because of the potential bleeding risk. Three recent randomized trials indicated that the benefit of aspirin was at best marginal in primary prevention and associated with significant bleeding risk.^1-3 The results from these trials caused the 2019 American College of Cardiology/American Heart Association (ACC/AHA) Primary Prevention guideline to downgrade their recommendation for consideration of aspirin to those at higher atherosclerotic cardiovascular disease (ASCVD) risk who were not also at an increased risk for bleeding鈥攁 difficult determination.⁴ The use of CAC to help identify appropriate candidates for aspirin is complicated by the increased bleeding risk in patients at increased cardiovascular risk.

Ajufo and colleagues examined observed bleeding and ASCVD events after a median follow-up of 12.2 years in a prospective population-based analysis of the Dallas Heart Study (DHS) cohort to characterize the association between CAC, bleeding, and ASCVD in 2191 participants (mean age 44; 57% women; 47% black) with no ASCVD or aspirin use at baseline.⁵ Participants included those at increased risk for bleeding. Patients also underwent CAC testing and were stratified into groups based on CAC score of 0, 1-99, and 鈮�100. The investigators then applied meta-analysis鈥揹erived aspirin effect estimates to observed ASCVD and bleeding rates to model the net impact of aspirin at different CAC thresholds.

There were 116 major bleeding and 123 ASCVD events over the entire follow-up period. Those in the highest CAC group had an unadjusted hazard ratio (HR) of 2.6 (95% CI, 1.5-4.3; P<.001) for bleeding events and 5.3 (95%CI, 3.6-7.9; P<.001) for ASCVD events compared with those in the lowest CAC group. The adjusted HR for bleeding in those with CAC considered high (鈮�100) versus low (0) was reduced after accounting for multivariable risk factors (1.5, 95% CI, 0.8-2.6; P=.19). However, the association between CAC and ASCVD events remained significant. The findings did not change in the subset of patients without incident aspirin use.

Aspirin use resulted in net harm among those with low (<5%) and intermediate (5%-20%) 10-year ASCVD risk regardless of CAC score, according to meta-analysis estimates. But aspirin use resulted in a net benefit in those at high (20%) 10-year ASCVD risk. The meta-analysis also found that those with a CAC score of at least 100, a lower bleeding risk, and a 10-year ASCVD score of at least 5% would have a net benefit. Those at higher bleeding risk would experience a net harm with aspirin use, regardless of their CAC score or 10-year ASCVD risk.

鈥淥ur study demonstrated that there may be subgroups of individuals for which aspirin may still be net beneficial for primary prevention of ASCVD,鈥� says the study鈥檚 senior author, Amit Khera, MD, MSc, director, preventive cardiology, UT Southwestern Medical Center. 鈥淭hese individuals include those with CAC >100 who are at low bleeding risk. Our results suggest that in this group, the number of ASCVD prevented with ASA is greater than the number of major bleeding events caused.鈥�

Based partly on these findings, a scientific statement from the National Lipid Association recently recommended that daily aspirin use in patients with CAC 鈮�100 is reasonable for those not at high risk for bleeding.⁶ The lead author of that scientific statement provided additional perspective on the current and future clinical utility of CAC scoring. 鈥淐AC scoring is an important tool to help us to properly allocate important preventive therapies, including statins, non-statin lipid lowering therapy, aspirin and anti-hypertensive drug therapy,鈥� says Carl E. Orringer, MD, director of preventive cardiovascular medicine at the University of Miami Miller School of Medicine.

鈥淣ew vistas for coronary calcium scoring include the development of new scoring systems that improve on the Agaston scoring system for ASCVD risk prediction, and include, in addition, quantification of calcification in the aortic valve and aorta, and measurement of epicardial, pericardial, and liver fat,鈥� added Orringer.

Khera says further work is needed to generalize the findings from this and other studies. 鈥淲e need to determine if these results are consistent in different demographic groups before applying these results more broadly.鈥� Nevertheless, he says, the current primary prevention guidelines⁴ should be updated to include the subset of patients who may benefit from aspirin. 鈥淥ur study provides a subgroup where aspirin may still be beneficial, based on CAC results, which is a well-established marker of risk.鈥�

Published: March 04, 2021