By: Dr. Geoffrey Modest
The American College of Cardiology meeting this week had several papers of potential clinical importance. One was on the relative utility of using coronary CT angiography (CTA) vs stress testing (functional testing) in patients with likely symptomatic coronary artery disease (CAD) — see DOI: 10.1056/NEJMoa1415516 — the PROMISE trial, an NIH supported study.
Details:
–10,003 symptomatic patients who were felt to need non-urgent cardiac testing were randomly assigned CTA vs exercise testing (regular ETT in 10.2%, nuclear stress testing in 67.5%, or stress echo in 22.4%; 29.4% of these tests were pharmacologic), with median 25 months of follow-up.
–Mean age 60.8, 52.7% women, 22.6% minority, 87.7% had chest pain (72.7%) or dyspnea on exertion (14.9%). Mean pretest prob of CAD was 53.3%. Also 21.4% had diabetes, 65.0% hypertension, 51.1% current or past tobacco use, 32.1% had family history (and patients had a mean of 2.4 of these 5 risk factors). 25% were on b-blockers, 44% on ACE-I/ARB, 46% on statins, 45% on aspirin (which seems a bit low, to me — given the high risk, I would likely have had almost all of them on almost all of these…..)
–Assessed composite primary endpoint of death, MI, hospitalization for unstable angina, or major procedural complication; secondary end points were invasive cardiac cath that did not show obstructive CAD and cumulative radiation exposure
Results:
–primary endpoint in 3.3% of the CTA group and 3.0% of the functional-testing: adjusted HR of 1.04 (0.83-1.29), p=0.75. During followup of up to 42 months, there was pretty consistently no difference in the Kaplan-Meier estimates.
–CTA was associated with fewer caths showing no obstructive CAD (3.4% vs 4.3%), p=0.02, though more in the CTA group underwent cath within the first 90 days (12.2% vs 8.1%)
–median cumulative radiation exposure was lower in CTA group (10.0 mSv vs 11.3 mSv) but 32.6% of the functional testing group had no exposure, so the overall mean exposure was higher in the CTA group (12.0 mSv vs 10.1 mSv), p<0.001. Of note, the cumulative radiation exposure also depends on the exposure from the functional test chosen (ie, nuclear test is lots more than echo or regular ETT…), so the exposure in the group with non-nuclear functional testing was much lower than the CTA group.
–also, of those who had cath within the first 90 days, 27.9% of the CTA group and 52.5% of the functional testing group had no obstructive CAD (which raises the possible alternative and untested strategy of functional testing, which could lead to CTA prior to going to invasive cath).
–and revascularization rates (not an endpoint of the study) were higher in those in the CTA group (6.2% vs 3.2%) (and as noted there was no difference in primary endpoints, raising also the untested assumption in this study of whether all of those who had caths really needed them…)
So, I must admit that the conclusion that CTA did not improve clinical outcomes makes sense on a number of levels.
–As in many of my prior blogs, I am very concerned about radiation exposure, and almost anything that might reduce it is a positive (and this is of huge public health significance, since about 4 million stress tests are done annually in the US). And I would extend my concern to the very frequent use of nuclear stress testing
–On a physiologic level, it makes a lot more sense to do a functional test, such as an exercise test, as opposed to just looking at how the coronary arteries appear on xray. For a few reasons:
–symptoms do not necessarily correlate with degrees of stenosis (there are many asymptomatic patients who have very severe or total coronary occlusion)
–future cardiac events do not correlate with degree of stenosis (old studies have shown that 78-97% of lesions in patients with acute coronary syndromes were <75% stenotic and half were <50% stenotic, reflecting the fact that acute events tend to occur after plaque disruption, and the most disruptable plaques are those with large lipid cores, which also have more inflammatory cells inside, but also may be small in overall size)
–and, it just makes sense to look at how a potential problem affects the individual person, since our relatively primitive models do not reflect the complexity of actual diseases and how the body responds (ie, there may be large-scale changes, such as angiogenesis/developing collaterals, or small-scale ones, such as changes in microvasculature and vascular auto-regulation, and, no doubt, some we know nothing about). It’s a bit like thyroid disease. some patients with the same free T4 levels may have functional hypo- or hyperthyroidism. The best test in general is the TSH, which really reflects how the individual’s body perceives the adequacy of the circulating thyroid hormones.
–and, as another sideline, over the past several years we have been moving towards treating non-urgent angina as a medical problem and not an invasive/surgical one (a conclusion supported by but not proved by this study). I would also suggest that in patients like these, where the pretest probability of CAD was >50%, it probably would have made sense from the beginning to have been on a more aggressive medical regimen.