Approximately half of the acute coronary syndromes that recur within 3 years of an index ACS treated percutaneously involve a different lesion that was visualized on angiography at that time but was not severe enough to require treatment, according to a report in the Jan. 20 issue of the New England Journal of Medicine.
Dr. Gregg W. Stone
The rate of recurrent major adverse cardiovascular events was 20% in this multicenter prospective study involving 697 patients with ACS who were successfully treated with PCI and medical therapy, then followed for 3 years, said Dr. Gregg W. Stone of Columbia University Medical Center/New York Presbyterian Hospital and the Cardiovascular Research Foundation, New York, and his associates.
They conducted the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study using new imaging tools that help characterize the content of coronary lesions, to identify factors that raise the risk for recurrent ACS.
The study, conducted at 37 medical centers in the United States and Europe, was funded by Abbott Vascular and Volcano. Abbott participated in the study design, site selection, data collection, and data analysis.
Study subjects were enrolled after undergoing successful and uncomplicated PCI for all coronary lesions thought to be responsible for their index ACS. At that time, the subjects underwent angiography, then conventional gray-scale intravascular ultrasonography and the newly available radiofrequency intravascular ultrasonography of the left main coronary artery and the proximal 6-8 cm of each of the major epicardial coronary arteries.
Unlike the other imaging techniques, radiofrequency intravascular ultrasonography provides data about tissue composition. It allowed the investigators to classify coronary lesions as thin-cap fibroatheroma, thick-cap fibroatheroma, pathologic intimal thickening, fibrotic plaque, or fibrocalcific plaque.
The median age of the study subjects was 58 years; 24% were women, and 17% had diabetes.
"We found that approximately one in five patients with [ACS] ... had recurrent major adverse cardiovascular events within 3 years. Events were nearly equally divided between those related to initially treated lesions and those related to previously untreated lesions," Dr. Stone and his colleagues said.
"Most events were rehospitalizations for unstable or progressive angina; death from cardiac causes, cardiac arrest, and MI were less common," they noted.
Radiofrequency intravascular ultrasonography at baseline revealed that most of the "nonculprit" coronary lesions – those that had been considered mild on the index angiography and were not treated at that time – were characterized by a large plaque burden, a small luminal area, or both. Half of them also were thin-cap fibroatheromas. These traits had not been visible on conventional angiography.
In contrast, no major events arose from arterial segments with a plaque burden that blocked less than 40% of the lumen. And nonfibroatheromas rarely caused such events, regardless of their plaque burden or the luminal area they blocked.
These study findings suggest that thin-cap fibroatheromas, lesions with a large plaque burden, and lesions with a small luminal area are particularly prone to cause recurrent ACS.
However, "there are several reasons why the methods we have used are not currently suitable for clinical application as a means of identifying sites in the coronary vasculature for potential intervention," the investigators noted (N. Engl. J. Med. 2011:364:226-35).
First, this method lacks specificity at present. Radiofrequency intravascular ultrasonography identified a total of 595 thin-cap atheromas in these subjects, but only 26 of them caused recurrent ACS. Similarly, fewer than 10% of the lesions that carried plaque burdens of 70% or more and the lesions with a 4-mm or smaller luminal area caused recurrent ACS.
"Even when all three predictive variables were present, the event rate rose to only 18%," they said.
Second, catheters used for this type of ultrasonography could only access the proximal 6-8 cm of the coronary tree. This meant that only 51 of the 106 "nonculprit" lesions seen on angiography could be evaluated by radiofrequency intravascular ultrasonography.
Third, the technique was associated with very serious adverse events in 11 patients in this study: 10 coronary dissections and 1 perforation, which in turn caused 4 nonfatal MIs.
And fourth, it is still unclear what therapies should be used when the technique identifies these high-risk lesions.
CLARIFICATION, 1/26/2011: The original version of this article did not list disclosures, which are included below.
PROSPECT and was funded by Abbott Vascular and Volcano. Abbott participated in the study design, site selection, data collection, and data analysis.
Dr. Stone reports receiving grant support, consulting fees, and/or lecture fees from numerous pharmaceutical and device firms, including Abbott Vascular, TherOx, the Medicines Company, Boston Scientific, Merck, Edwards Lifesciences, Bioabsorbable Therapeutics, Asten BioPharma, AstraZeneca, Prescient, Eli Lilly, Bristol-Myers Squibb,and Sanofi-Aventis; and owning stock or stock options in numerous companies including CoreValve, Savacor, Xtent, FlowCardia, Ovalum Vascular, and MediGuide. Other investigators reported financial relationships with Abbott Vascular, Boston Scientific, Volcano, Bristol-Myers Squibb, Sanofi-Aventis, the Medicines Company, and others.