Coronary Artery Calcium Trial Fails to Impress

CAUGHT-CAD is actually a randomized controlled trial using CAC, but it fails to support use of CAC imaging. It is the Study of the Week.

The Journal of the American Medical Association published an actual randomized controlled trial for coronary artery calcium (CAC).

As a skeptic of this imaging test, I saw the headline and thought: finally, we will learn whether patients who have their chest radiated have better outcomes.

Better outcomes, such as fewer heart attacks or strokes, or longer life, is why we interact with healthcare. For instance, we don’t take a medicine to achieve a lower level of a lab test or a smaller size of tumor on a scan; we take the medicine in hopes of living longer with fewer bad events.

Same with imaging tests. When you have your body interrogated, you do so in hopes that it produces better outcomes. For instance, when we do a coronary angiogram during an acute myocardial infarction (MI) we know—from trials—that doing so leads to opening of a closed artery, and that strategy is better than giving a clot-busting drug.

Alas, the positive CAUGHT-CAD trial in JAMA does not study use of the CAC score to improve an important clinical outcome.

The Trial

The authors asked the question of whether combining CAC score with a preventive strategy can be used to reduce plaque progression in intermediate-risk patients with a family history of CAD.

This was a prospective randomized open-label trial done in 7 hospitals in Australia. Patients were asymptomatic adults who had a first degree relative with CAD before age 60.

The authors randomized about 450 patients to either the CAC-score informed group vs standard care. The mean CAC score in both groups was 64-72. The average estimated 10-year risk (from the pooled cohort equation) was 6.6%-7.2%, so, basically, this trial studied patients just below the ACC, AHA threshold for statins at 7.5%

The CAC-informed group was nurse led in which the participants CAC images were used to communicate about disease. And, importantly, after all this education, everyone in the intervention group started lipid-lowering therapy, most often with a statin.

The usual care group had standard education about CAD prevention from their general practitioner who was blinded to the CAC score. None of these patients were recommended for statins.

The primary endpoint of this trial was not MI, stroke, or CV death; it was total plaque volume, with further analysis for calcified and noncalcified plaque volume on a coronary CT scan done at three years. IOW, the primary outcome was a surrogate measure for an important outcome. (I will come back to this.)

Trial Results

After 3 years of follow-up, the CAC score-informed group showed significantly greater reductions LDL-C levels compared to usual care. This however should be obvious because one group got statins and the other did not.

The primary outcome of total plaque progression was significantly lower in the CAC score-informed group compared to usual care (15.4 vs. 24.9 mm³, p=0.009).

Trial Conclusions and Editorials

The authors wrote that

“these data support the use of CAC score to assist intensive preventive strategies in intermediate-risk patients.”

Two editorials accompanying the manuscript were highly supportive.

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My Comments

I don’t agree. For two main reasons.

A weak surrogate endpoint: Plaque imaging is a surrogate measure of coronary artery disease. It’s difficult to measure, as evidence by exclusion of 13% of individuals excluded because of technical imaging issues.

But even if imaging were perfect, no one knows whether reducing plaque on a scan reduces important outcomes like heart attack or stroke or death from heart disease.

I realize that sentence may seem strange to some readers. Because it makes sense that less plaque would lead to better outcomes.

The problem is that surrogate markers of health don’t always pan out. For instance, Dr David Brown and colleagues studied nearly every trial in atherosclerotic heart disease and found that the outcome of myocardial infarction (actual heart attack) was a poor surrogate for death or CV death.

This was a disruptive paper because you would think that an intervention that led to fewer MIs would reduce the odds of dying from heart disease, but it did not. And it was especially true in recent years, because, as MIs become easier to diagnose through super-sensitive enzyme tests (high-sensitivity troponin), their value as a surrogate measure of heart health lessened.

So…if an actual MI is a poor predictor of heart health, than an image of a blood vessel is even less valuable as a surrogate.

A flawed comparison: But even if we pretend that plaque imaging was a reasonable measure of health, CAUGHT-CAD is really a study of a strategy of statin use vs non-statin use.

The authors suggest that a nurse showing patients an image of the scan helped them live better over the three years, which then led to better scans.

But the nurse-led group also received a medicine known to reduce LDL-C while the other group did not get the statin. I don’t see how CAC figures in the outcome given this huge difference in strategy.

Final Conclusion

I stand by the argument that Andrew Foy and I made that CAC imaging has no role in improving cardiovascular health.

The Internet overflows with stories—often from tech titans—where a CAC scan led to a lifesaving stent in a previously unknown coronary obstruction. But we know from many clinical trials that outside of an acute MI, revascularization (stenting) does not lead to better outcomes over simple medical and lifestyle therapy.

The proponents of CAC imaging, however, could persuade me.

To do so, they need to randomize enough patients to a trial of CAC imaging vs no-CAC imaging to show that radiating a person reduces future major adverse cardiac events. Studies like CAUGHT-CAD don’t come close to that.

Proponents of CAC might say such a trial can’t be done because it would require too many patients. A statement that supports my point.