PROSPECT Assesses Impact of Nonculprit Lesions

September 25, 2009—Gregg W. Stone, MD, presented results from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study showing that culprit and nonculprit lesions contribute equally to the risk of 3-year adverse events in acute coronary syndrome (ACS) patients treated with stents and medical therapy. The data were presented at the Transcatheter Cardiovascular Therapeutics (TCT) 2009 annual scientific symposium in San Francisco and reported in the conference's newspaper, TCT Daily. Abbott Vascular (Santa Clara, CA) sponsored the study.

According to Dr. Stone, the PROSPECT investigators sought to quantify the clinical event rate due to atherosclerotic progression and to identify those lesions that place patients at risk for unexpected adverse cardiovascular events.

TCT Daily reported that PROSPECT is the first prospective natural history study of atherosclerosis using multimodality imaging to characterize the coronary tree. The study found that identification of lesions can be enhanced by intravascular ultrasound (IVUS) and virtual histology (VH). Dr. Stone stated that most cases of sudden cardiac death and myocardial infarction (MI) are believed to arise from plaque rupture with subsequent thrombotic coronary occlusion of angiographically mild lesions (vulnerable plaques) but the prospective detection of which has not been achieved. The event rate attributed to progression of such lesions has never been prospectively studied, he added.

PROSPECT included 700 patients with ACS—either ST-elevation myocardial infarction (STEMI) within 24 hours (30.3%), non-STEMI (65.6%), or unstable angina with electrocardiogram changes (4.2%)—who underwent successful percutaneous coronary intervention in one or two major coronary arteries at 37 centers in the United States and Europe. The investigators performed quantitative coronary angiography of the entire coronary tree, IVUS, and VH.

Over a median follow-up period of 3.4 years, the culprit and nonculprit lesions led to similar levels of major adverse cardiac events (MACE), a composite of cardiac death, cardiac arrest, MI, unstable angina, and increasing angina. Half of the events occurred within 1 year, and half occured between 1 and 3 years.

The nonculprit lesions were not linked to any cases of cardiac death or arrest but were most commonly associated with increasing angina (8.5%), unstable angina (3.3%), and MI (1%). If all of the deaths that could not be definitively linked to either a culprit or nonculprit lesion were attributed to the nonculprit lesions, the worst-case scenario would be a combined cardiac death/cardiac arrest/MI rate of 3.3% in that group, Dr. Stone said.

Baseline clinical and angiographic factors were poor predictors of nonculprit lesion-related events. Insulin-dependent diabetes was the strongest risk factor (hazard ratio = 4.07; 95% confidence interval, 1.75–9.46). IVUS characteristics and VH plaque type, however, were much more informative. Among them, multivariable analysis found five independent predictors of events.

According to Volcano Corporation (San Diego, CA), which provided the VH imaging technology for PROSPECT, its VH IVUS uses spectral analysis of the ultrasound signal to classify atherosclerotic disease into different plaque components. By using these four plaque components, the PROSPECT investigators grouped the baseline lesions into five distinct lesion types (fibrotic, fibrocalcific, pathological intimal thickening, thick-cap fibroatheroma, and thin-cap fibroatheroma) in order of hypothesized risk.

"The prospective identification of nonculprit lesions prone to develop MACE within 3 years can be enhanced by characterization of underlying plaque morphology with virtual histology, with virtual histology thin-cap fibroatheromas (VH-TCFA) representing the highest-risk lesion type," concluded Dr. Stone. "Specifically, the combination of large plaque burden detected by IVUS and a large necrotic core without a visible cap, that is, a VH-TCFA, identifies lesions that are at especially high risk for future adverse cardiovascular events."