Thin-Cap Fibroatheromas May Help Explain Poor PCI Outcomes in Diabetic Patients

After undergoing successful PCI, diabetic patients with ACS have a markedly higher risk of major adverse cardiac events—particularly those arising from nonculprit lesions—when at least one IVUS-identified thin-cap fibroatheroma (TCFA) is present, an analysis of the PROSPECT study shows. But among patients without this feature, outcomes are similar regardless of diabetes status.

The presence of untreated TCFAs explains “to a large extent the poor prognosis of the high-risk diabetic cohort,” lead author Elvin Kedhi, MD, PhD (Isala Klinieken, Zwolle, the Netherlands), and colleagues report in a study published online June 29, 2016, ahead of print in JACC: Cardiovascular Imaging.

According to Pedro Moreno, MD (Mount Sinai Hospital, New York, NY), who was not involved in the research, the study is an important addition to the literature on the controversial vulnerable plaque hypothesis—namely, that plaques most likely to rupture and cause events can be identified and potentially treated to prevent poor outcomes.

The vulnerable plaque field has suffered because patient selection has been challenging, he told TCTMD. “It is certainly a field that is promising, but the selection needs to be tailored to high-risk patients who will actually benefit from potential therapies before the vulnerable plaque evolves into a major cardiovascular event,” he said.

The main findings of the PROSPECT study showed that certain IVUS-identified high-risk plaque characteristics, including TCFA morphology, were associated with an increase in cardiovascular events, but they were present in only about 5% of the study population, Moreno noted.

The current analysis is significant, he said, in that it identifies a subgroup with a very high risk for events—diabetics with TCFA morphology.

It is already known that diabetics carry an elevated risk of cardiovascular events and need very aggressive therapy to control risk factors, but before moving forward with an imaging-based approach to treatment, the field requires confirmation of the vulnerable plaque hypothesis in prospective studies, Moreno said.

The current analysis “is hypothesis-generating and the best [next step] will be to design a randomized trial with enough power in diabetic patients to see if the segment-related therapies with drug-eluting stents, bioresorbable scaffolds, or others will reduce events,” he said.

Significance of TCFA

PROSPECT enrolled 697 patients with ACS (17.7% with diabetes) after successful and uncomplicated PCI of all angiographically-evident culprit coronary lesions. The current analysis was aimed at clarifying the contribution of TCFA morphology to the higher risk seen in patients with diabetes.

In an unadjusted analysis, the 3-year rate of MACE (death from cardiac causes, cardiac arrest, MI, or rehospitalization due to unstable or progressive angina) was, as expected, higher in patients with versus without diabetes (29.4% vs 18.8%; P = 0.01). The difference was driven primarily by a higher rate of events arising from nonculprit lesions (18.7% vs 10.4%; P = 0.02). The findings were similar in a propensity-matched analysis, although the difference in nonculprit MACE fell shy of statistical significance, “likely because of reduced power,” the authors say.

Among diabetic patients, those who had at least one TCFA had a higher risk of nonculprit MACE at 3 years compared with those who had none (27.8% vs 8.9%; HR 3.56; 95% CI 0.98-12.96; P = 0.04).

Diabetic patients with no TCFAs had a similar risk of nonculprit MACE compared with all nondiabetic patients (8.9%; HR 1.09; 95% CI 0.27-4.41) and nondiabetic patients who did not have TCFAs (5.2%; HR 1.69; 95% CI 0.28-10.10).

The authors say their work extends the results of a prior study showing that patients with versus without diabetes were more likely to have at least one nonculprit lesion that contained multiple high-risk plaque features associated with future unanticipated MACE.

Vulnerability of the Whole Patient

In an accompanying editorial, Stephen Nicholls, MBBS, PhD (South Australian Health and Medical Research Institute, Adelaide, Australia), and colleagues, note that the heterogeneity of cardiovascular risk in diabetic patients has spurred a search for ways to identify those who would benefit from more intensive interventions.

“This is one area in which arterial wall imaging presents considerable opportunity, by virtue of the ability to reliably visualize the full extent of atherosclerotic plaque within a range of vascular territories,” they say.

The new findings “add to a growing body of evidence and interest in the concept that atherosclerotic plaque imaging may play an important role in identifying patients who should be treated more intensively,” Nicholls et al say, adding, however, that “whether plaque imaging can identify a patient who is more likely to benefit from use of more intensive therapeutic intervention remains to be determined.”

Despite interest in the concept of vulnerable plaque, however, “there has been increasing recognition that not all events are precipitated by plaque rupture,” the editorialists write, pointing to plaque erosion as another potential mechanism. Also, they say, events can arise from lesions that do not meet criteria for plaque vulnerability.

“This continues to reinforce that it is the vulnerability of the whole patient, as opposed to individual lesions, which is more likely to be of use in risk prediction and triage of patients to additional interventions,” they argue.

“Whether measures of plaque composition truly provide incremental risk prediction above and beyond plaque burden remains debatable,” they conclude. “To what degree this truly influences cardiovascular outcomes remains poorly studied in prospective, randomized clinical trials. The time has come for those trials to provide such data to inform how best to integrate imaging into our practice.”

Note: Two of the study authors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.



Related Stories:

  • Kedhi E, Kennedy MW, Maehara A, et al. Impact of thin-cap fibroatheromas on unanticipated ischemic events in medically-treated patients with diabetes mellitus: insights from the PROSPECT study. JACC Cardiovasc Imaging. 2016;Epub ahead of print.

  • Nicholls SJ, Andrews J, Psaltis PJ. Using imaging to identify the high-risk diabetic patient: are we any closer? JACC Cardiovasc Imaging. 2016;Epub ahead of print.

  • Kedhi and Moreno report no relevant conflicts of interest.
  • Nicholls reports being a principal research fellow of the National Health and Medical Research Council of Australia; having received research support from AstraZeneca, Cerenis, Novartis, Eli Lilly, Amgen, Resverlogix, InfraReDx, The Medicines Company, Sanofi-Regeneron, and Anthera; and serving as a consultant for AstraZeneca, Amgen, Eli Lilly, Pfizer, Merck, Takeda, Roche, CSL Behring, Boehringer Ingelheim, and Sanofi-Regeneron.

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