Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019
Key result
CAC ≥100 identifies net benefit from primary prevention aspirin with a 5-year NNT of ~140.
- NNT 140
- NNT 140
- n=6,470
Why the study?
Guidelines recommend considering low-dose aspirin in adults 40 to 70 years old at higher ASCVD risk without high bleeding risk, but how to best identify these patients remains unclear.
Does coronary artery calcium (CAC) scoring improve the personalized allocation of aspirin for primary prevention compared to pooled cohort equations in adults <70 years without high bleeding risk?
Population
6470 participants from the MESA Study
Comparison
CAC score strata vs pooled cohort equations ASCVD risk strata
Design
Observational cohort study with modeled benefit-harm analysis
Authors
Discussion
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Member takes
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Even if we're treating people optimally right now with the usual preventive therapies, which usually means treating their blood pressure and giving them cholesterol lowering medication if they need it, there are still people who are on all of those appropriate treatments and get a heart attack, so there's an interest in trying to find additional ways to help people prevent heart attacks and seeing if aspirin is one of the ways that we could do that.”
“We know that aspirin can reduce nonfatal CVD in primary prevention, but the number-needed-to-treat for this is about 250 patients, so most primary-prevention adults taking aspirin don't stand to benefit. Also, the number needed to harm is also about 200 to 250 patients, mostly from bleeding. Elevated CAC is one way to identify adults where the NNT is more favorable than the average of 250 and where the benefit ratio for a given primary-prevention adult justifies consideration of aspirin and a discussion with the patient.”
“Numerous studies have shown that coronary artery calcium score can identify people at risk of future heart attack and stroke above and beyond traditional risk factors such as cholesterol and blood pressure. Similarly, several studies including MESA (the largest multi-ethnic study of heart disease in the US) have demonstrated that individuals without a history of heart disease but with a high coronary calcium score can benefit from aspirin. This should be highlighted in the recent news related to the updated ACC/AHA Guidelines published last week.”
Implication
May refine aspirin allocation in primary prevention; leaves open whether randomized trials will confirm benefit over risk equations.
Key Points
- To assess the value of coronary artery calcium (CAC) scoring compared with standard pooled cohort equations for guiding low-dose aspirin allocation in the primary prevention of cardiovascular disease.
- Evaluated 6,470 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) stratified by pooled cohort equation 10-year risk (<5%, 5% to 20%, >20%) and baseline CAC scores (0, 1 to 99, ≥100, ≥400).
- Restricted primary benefit/harm calculations to aspirin-naive participants <70 years of age without high bleeding risk features (n=3,540), modeling a 12% relative risk reduction for cardiovascular events and a 42% relative risk increase for major bleeding.
- Overall, the 5-year number needed to treat (NNT5) to prevent 1 cardiovascular disease event was 476, which was unfavorable compared to the 5-year number needed to harm (NNH5) of 355.
- A CAC score ≥100 identified individuals who derived net benefit (NNT5=140 vs NNH5=518) and independently predicted cardiovascular events compared to CAC=0 (HR 3.9, 95% CI 2.5 to 6.1).
- A CAC score of 0 identified participants where aspirin was projected to cause net harm (NNT5=1190 vs NNH5=567), a pattern that persisted even among individuals with estimated 10-year risk >20%.
Study Design
Type
Cohort (n=6,470)
Multicenter
Yes
Structured PICO
Does coronary artery calcium (CAC) scoring improve the personalized allocation of aspirin for primary prevention compared to pooled cohort equations in adults <70 years without high bleeding risk?
P
Population
6,470 adults aged 45 to 84 years free of baseline cardiovascular disease, with a subgroup of 3,540 aspirin-naive participants under 70 without high bleeding risk followed for over 14 years to assess CAC-guided aspirin allocation.
E
Exposure
Modeled allocation of low-dose aspirin for primary prevention based on coronary artery calcium (CAC) score.
C
Comparator
Modeled allocation based on pooled cohort equations (PCE) estimated 10-year ASCVD risk.
O
Outcome
5-year number needed to treat (NNT5) for cardiovascular disease events (composite of fatal/non-fatal MI, fatal/non-fatal stroke, and other CVD death) versus 5-year number needed to harm (NNH5) for major bleeding events.composite
Main Result
Number Needed to Treat: 140
Number Needed to Treat: 140
Coronary artery calcium scoring may be superior to pooled cohort equations for identifying patients who will derive a net benefit from aspirin in primary prevention, particularly those with CAC ≥100.
Limitations
- Heterogeneity in the meta-analysis populations used for relative risk reduction and increase estimates.
- Inability to assess certain high bleeding risk features like history of gastrointestinal ulcers at baseline.
- Use of ICD codes for bleeding events may have led to false positives.
- Small sample size of statin users precluded subgroup analyses by baseline statin use.
- Observational design means findings are hypothesis-generating and require experimental confirmation.
- Heterogeneous populations in the pooled meta-analysis compared to MESA
- Limited ability to identify individuals with high bleeding risk (e.g., history of GI ulcers not assessed)
- Ascertainment of hospitalized bleeding cases using ICD codes may have led to false positive events
- Subgroup analyses by baseline statin use precluded by sample size
- Atherothrombotic and bleeding events assumed to be equivalent
- Observational nature of the study
Cite This Study
Cainzos‐Achirica et al. (2020) conducted a cohort in Primary prevention of cardiovascular disease (n=6,470). Coronary artery calcium (CAC) score ≥100 vs. CAC = 0 was evaluated on 5-year Number Needed to Treat (NNT) to prevent 1 cardiovascular disease event (NNT 140). A coronary artery calcium score ≥100 identified individuals likely to derive net benefit from aspirin for primary prevention, with a 5-year number needed to treat of 140 versus a number needed to harm of 518.