PROSPECT Study of Coronary Atherosclerosis Published

January 20, 2011—In the New England Journal of Medicine, Gregg W. Stone, MD, et al have published findings from PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), a prospective natural history study of coronary atherosclerosis (2011;364:226-235).

According to the PROSPECT investigators, atherosclerotic plaques that lead to acute coronary syndromes often occur at sites of angiographically mild coronary artery stenosis but lesion-related risk factors for such events are poorly understood.

As detailed in the New England Journal of Medicine, 697 patients with acute coronary syndromes underwent three-vessel coronary angiography and grayscale and radiofrequency intravascular ultrasound (IVUS) imaging after percutaneous coronary intervention. Subsequent major adverse cardiovascular events (death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization due to unstable or progressive angina) were adjudicated to be related to either originally treated (culprit) lesions or untreated (nonculprit) lesions. The median follow-up period was 3.4 years.

The investigators reported that the 3-year cumulative rate of major adverse cardiovascular events was 20.4%. Events were adjudicated to be related to culprit lesions in 12.9% of patients and to nonculprit lesions in 11.6%. Most nonculprit lesions that were responsible for follow-up events were angiographically mild at baseline (mean [± SD] diameter stenosis, 32.3% ± 20.6%). However, on multivariate analysis, nonculprit lesions that were associated with recurrent events were more likely than those that were not associated with recurrent events to be characterized by a plaque burden of 70% or greater (hazard ratio [HR], 5.03; 95% confidence interval [CI], 2.51–10.11; P < .001), a minimal luminal area of 4 mm² or less (HR, 3.21; 95% CI, 1.61–6.42; P = .001), or on the basis of radiofrequency IVUS as thin-cap fibroatheromas (HR, 3.35; 95% CI, 1.77–6.36; P < .001).

The investigators found that in patients who presented with an acute coronary syndrome and underwent percutaneous coronary intervention, major adverse cardiovascular events occurring during follow-up were equally attributable to recurrence at the site of culprit lesions and to nonculprit lesions. Although nonculprit lesions that were responsible for unanticipated events were frequently angiographically mild, most were thin-cap fibroatheromas or were characterized by a large plaque burden, a small luminal area, or some combination of these characteristics, as determined by grayscale and radiofrequency IVUS, the investigators concluded.

Abbott Vascular (Santa Clara, CA) and Volcano Corporation (San Diego, CA) sponsored the PROSPECT study.

According to Volcano, the study showed that grayscale IVUS and Volcano's virtual histology (VH) IVUS tissue-characterization software enable physicians to more accurately assess the risk of individual blockages than with the use of the current standard-of-care, angiographic imaging alone. Volcano stated that the PROSPECT study showed that of the 55 imaging parameters measured, grayscale IVUS and VH IVUS identified the only individual parameters that could statistically predict lesion risk for future clinical events. When used together, grayscale IVUS and VH IVUS uncovered lesion characteristics that PROSPECT showed to predict the highest lesion risk for future clinical events.

“The landmark PROSPECT study has confirmed two key principles that will be relevant as we continue to innovate and improve our treatment of cardiovascular disease,” commented Dr. Stone. “First, angiographic guidance alone is not a good predictor of future events; grayscale IVUS is much better than angiography at determining the severity of plaque, and which blockages are most likely to cause future events. Second, all coronary artery disease is not the same, and differences in underlying tissue type can in fact change the risk profile of a lesion. Some blockages are more active and can quickly progress to a clinical event. Other blockages are more stable, and when combined with proper medical therapy, have an extremely low risk of causing a future event. For the first time, we have been able to prospectively identify these lesions both by size and by tissue type using VH IVUS.”