MESA Analysis: CAC Scores Predict Aspirin Benefit in Primary Prevention

May 06, 2014

MINNEAPOLIS, MN — Predicted benefit from daily aspirin therapy for primary prevention exceeds risk when coronary artery calcium (CAC) imaging scores reach or exceed 100, whereas the risks surpass benefits at a CAC score of 0, in both cases regardless of risk by Framingham criteria, suggests analysis of a Multi-Ethnic Study of Atherosclerosis (MESA) cohort[1]. Those with CAC scores of 0 or >100 accounted for three-fourths of the ethnically diverse (only 37% white) population of >4200 nondiabetic persons not on aspirin at baseline.

In such patients, who may be considered candidates for the daily therapy by conventional criteria, calcium scores "have potential utility to decide who should take aspirin and who shouldn't," Dr Michael D Miedema (Minneapolis Heart Institute, MN) told heartwire . Miedema is lead author on the analysis, published online today in Circulation: Cardiovascular Quality and Outcomes.

Based on pre-2013 guidelines from the American Heart Association, in which persons with a 10-year CHD risk of at least 10% qualified for daily aspirin, he said, almost a third of the current cohort who met those criteria had a CAC score of 0, suggesting they would be better off not taking it. And about a tenth of those not qualifying for daily aspirin had CAC scores of at least 100 and so would likely have gained from it, the research indicates.

The MESA analysis complements other research, including another from a MESA cohort published three years ago (and reported then by heartwire ), that concludes similarly about CAC scores and statin therapy, Miedema observed. In it, CAC scores using much the same cutoff values as the current analysis, in a statin-eligible cohort that would have qualified for the JUPITER trial, effectively stratified patients for risk of CVD and CHD events.

"These findings, combined with the results of our analysis, suggest that CAC may be useful in determining the potential benefit of both aspirin and statin therapy, thus increasing the use of CAC as a tool for improved clinical decision making," he and his colleagues write.

The group looked at 4229 MESA participants, without diabetes and not on aspirin at baseline, according to CAC scores and outcomes over the study's follow-up, averaging 7.6 years. After adjustment for potential confounders and other features, including Framingham risk level, the hazard ratios (HR) for "hard" CHD events (including nonfatal MI, resuscitated cardiac arrest, and CHD death) and of hard CVD events (including CHD events and fatal and nonfatal stroke) for CAC >100 vs CAC=0 went up by factors of 4 and nearly 3, respectively.

Adjusted* Hazard Ratios (95% CI) by CAC Burden vs CAC=0 in Nondiabetic, Nonaspirin MESA Cohort

CAC Score Range Population (%) CHD HR (95% CI) CVD HR (95% CI)
0 55.8 1.00 1.00
1–99 25.8 2.09 (1.18–3.70) 1.88 (1.21–2.92)
> 100 18.3 4.19 (2.36–7.43) 2.85 (1.81–4.50)
*Adjusted for age, sex, race, MESA site, smoking status, cigarette pack-years, body-mass index, LDL cholesterol, HDL cholesterol, dyslipidemia medication use, hypertension, antihypertensive medication use, MI family history, education level, and Framingham risk score

Looking at their cohort by sex, the group saw that CAC scores >100 signified a projected net benefit from daily aspirin for both men and women regardless of whether they qualified for daily aspirin by conventional guidelines. The risk/benefit equation pointed to greater risk from daily aspirin for men with a CAC score of 0 regardless of conventional guidelines. But for women, a CAC score of 0 was associated with a net harm from aspirin only if they were also at low risk by standard criteria; those at increased risk by standard criteria had a predicted net benefit from aspirin regardless of CAC score.

CAC screening was oversold for risk stratification, based on a thin evidence base, when it was introduced a few decades ago, Miedema observed. Also, it was prohibitively expensive for most people. "But now that the data have come out, it's clearly the best risk-stratification tool that we have, especially compared with any of the blood-based biomarkers." Although the price per scan varies around the US and "is mostly out of pocket," he said, in Minnesota, "most places charge $99 per scan, even $50 sometimes. So the cost has gone down pretty substantially. The radiation dose has been cut a fair amount too. We're down to about a half of a milliSievert, which is less [radiation exposure] than a mammogram, and we're talking about a one-time test that can decide whether [or not] you should take a medication."

On May 2, the Food and Drug Administration formally positioned itself against "the general use of aspirin for primary prevention of a heart attack or stroke," without broaching the subject of risk stratification in the primary-prevention setting for identifying potential aspirin candidates. It took the stance while squarely supporting aspirin for secondary prevention.

The agency said it is issuing the statement now because it "recently denied a request submitted by Bayer HealthCare," a citizen petition filed in February 2003, asking for a change in aspirin labeling that would allow its marketing for primary prevention. The FDA said it waited until now to allow consideration of aspirin primary-prevention studies in diabetics and patients with peripheral artery disease, which "did not demonstrate a significant benefit."

Interestingly, the FDA's letter denying Bayer's petition rejected the idea of "risk-based" labeling that would consider benefit in primary-prevention "subpopulations defined by demographics, risk assessments, or a combination of demographics and risk."

The authors had no disclosures.



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