Statin Effects in Nonobstructive CAD Hinge on Plaque Burden, CTA Reveals

Even in patients without obstructive coronary disease, the amount of coronary plaque seen on coronary CT angiography (CTA) tracks directly with the risk of subsequent MI and all-cause death, a large, observational study out of Denmark makes clear. Importantly, however, the impact of statins in attenuating that risk is also proportional to the amount of plaque burden.

The data offer support not only for the use of CTA in the setting of a chest-pain workup, but also for use of the information gleaned to guide statin prescription and other preventive medicine, the authors say. “The present study supports a new paradigm in which decision-making on preventive therapy is based on detection and quantification of CAD obtained from coronary CTA rather than a risk assessment based on traditional cardiovascular risk factors,” write Kristian A. Øvrehus, MD, PhD (Odense University Hospital, Esbjerg, Denmark), and colleagues.

Their paper, drawing on over 33,500 patients in the Danish National Patient Registry, was published online today in JACC: Cardiovascular Imaging.

Prior studies have carved out a role for coronary CTA in chest-pain patients, established the benefits of statins in patients with nonobstructive CAD, and linked plaque burden to events in stable CAD. But how the amount of plaque relates to outcomes in the setting of symptomatic nonobstructive disease or how plaque burden influences the correlation between statin prescription and events have been unclear.

Øvrehus and colleagues looked at outcomes a median of 3.5 years following CTA in 33,552 symptomatic patients found to have either no CAD (n = 19,669) or nonobstructive CAD (n = 13,883). Rates of MI or death ranged from four in 1,000 among those found to have no coronary disease up to 32 per 1,000 among those with severe nonobstructive CAD (coronary artery calcium score ≥ 400).

Statin therapy in the trial was assessed using national databases indicating filled and repeat prescriptions, both 90 days prior to coronary CTA and 90 days after, Øvrehus stressed to TCTMD—at least in theory a better indicator that patients were actually taking their medication than relying on self-report, as many other studies have done. Here, after multivariable adjustment, statin therapy was associated with a roughly 50% reduction in events across all categories of CAD (none, mild, moderate, or severe), but the number needed to treat (NNT) fell as plaque burden increased. So, in patients with mild nonobstructive disease, the NNT was 36 to prevent a death or MI, but fell to 13 in patients with severe, nonobstructive CAD.

“I think the 50% reduction of events by statins and the exact numbers needed to treat should be interpreted with some caution,” Øvrehus told TCTMD, given the retrospective nature of the data set and unmeasured confounders. “But I think the signal is there that there is a reduction.”

Even if confounders not accounted for in the modeling were responsible for 15% or 20% of the difference, the reduction in events would be in line with what’s been seen in the major statin trials, he said. “So I don't think the numbers are far off. I think it is quite reasonable to believe that [the reduction] is somewhere in that range. . . . I think the message is that the more coronary artery disease you have, the higher the risk. This can be modulated by statins, and it is worthwhile considering doing that.”

Image-Guided Therapy

Commenting for TCTMD, Benjamin Chow, MD (University of Ottawa Heart Institute, Canada), said the large observational study supports a number of findings established or hinted at in earlier studies—some of them hotly contested—including the notion that “image-guided medical therapy” can improve patient outcomes.

Chow gave the example of the randomized SCOT-HEART trial, in which patients randomized to a chest-pain workup strategy that included CTA fared better over the next 5 years than patients managed according to standard pathways. “This study supports the observation of the SCOT-HEART trial in which CCTA patients likely benefited from intensification of medical therapy” as a result of plaque visualization on imaging, Chow said in an email.

There are plenty of confounders to consider in the current paper, Chow added, including the lack of information on cardiac deaths, statin doses, and lifestyle changes. The takeaway appears to be that “the use of statins was associated with improved outcome, but the benefit and number needed to treat improved with the severity of nonobstructive plaque,” he said.

Coronary CTA in Denmark has been used as a first-line diagnostic tool for the better part of a decade, Øvrehus noted, telling TCTMD that he believes their study is not “affirmative” that it is the best approach in these patients. Rather, he said, it’s “supportive” of CTA as a helpful prognostic tool.

Chow, likewise, noted that many countries have endorsed the use of coronary CTA as a first-line diagnostic test for symptomatic patients and recommendations for it are widely expected to be strengthened in the upcoming American Heart Association/American College of Cardiology chest-pain guidelines.

“I agree that CCTA should play a greater role in diagnosis of patients with suspected CAD,” although it does have limitations, Chow said. “There are situations when other noninvasive or invasive tests may be more appropriate. Therefore CCTA is not a be-all-and-end-all test.

“Nonetheless,” he continued, “the results are exciting and [the study] brings us one step closer to ‘precision/individualized medicine,’ because it gives us the opportunity to tailor medical therapy according to the presence plaque—plaque that would otherwise not be visualized or detected with some of the other noninvasive cardiac modalities.”