Imaging endpoints prove successful in PROSPECT trial

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The preliminary results of the ongoing PROSPECT trial, the first study using multi-modality imaging to prospectively identify vulnerable plaque, indicate that the researchers have successfully performed qualitative catheter angiography of the entire coronary tree on a millimeter by millimeter level and that three-vessel intravascular ultrasound (IVUS) imaging is feasible in most patients.

Gregg Stone, MD, of Columbia University Medical Center and the chairman of the Cardiovascular Research Foundation, presented the preliminary findings at the Cardiovascular Revascularization Therapies (CRT) 2008 meeting in Washington, DC, last week.

The researchers began the trial to determine whether baseline demographics, biomarkers, angiography, IVUS and virtual histology can identify patients and lesions at risk for future adverse cardiovascular events.

Abbott Vascular and Volcano, maker of virtual histology IVUS, are sponsoring the trial.

The PROSPECT trial has enrolled at nearly 40 worldwide sites 697 patients with acute coronary syndrome with unstable angina or non-ST-elevation MI or STEMI >24º and one-to-two vessel coronary artery disease undergoing PCI.

The researchers are seeking to compare active and inflamed plaque to inactive and non-inflamed plaque. In particular, researchers are seeking to identify thin cap fibroatheroma, the precursor lesion of plaque rupture.

The patients underwent three-vessel imaging post-PCI in the culprit artery, followed by non-culprit arteries. The researchers performed qualitative catheter angiography (QCA of the entire coronary tree), followed by IVUS, virtual histology, and palpography in about 350 patients. The doctors recommended pharmaceutical therapy of aspirin, clopidogrel – up to one year, and statin treatment.

The researchers conducted follow-up at one month, six months, one year, two years and three to five years. Stone said that they repeated imaging in patients with events.

Baseline clinical features of the 697 patients were 30.3% who underwent STEMI in less than 24 hours; 65.4% non-STEMI patients; and 4.3% patients with unstable angina and stent thrombosis changes.

The mean number of IVUS lesions per patient at baseline with a mean luminal area (MLA) of less than 4 mm2 was 0.74. Nearly 60% of 612 patients had zero lesions per coronary tree; one-quarter had one; 8% had two; 4% had three; and 3.4% had four or more. There were a total of 453 lesions.

The PROSPECT methodology of IVUS/Virtual Histology Core Lab Analysis classified the lesions into 13 main sub-types based on virtual histology composition:
1. Fibrotic
2. Fibrocalcific
3. Pathological intimal thickening
4-9. Thick-cap fibroatheromas
10-13. Virtual histology thin-cap fibroatheroma (presumed high risk)
The ischemia-producing lesions are left behind.

The baseline features revealed the presence of at least one or more virtual histology lesion subtypes in 616 patients (2,381 total lesions):
  • 16.5% fibrotic
  • 33.1% fibrocalcific
  • 73.5% pathological intimal thickening
  • 67.2% fibroatheroma
  • 58.5% thick-cap fibroatheroma
  • 28.4% thin-cap fibroatheroma
Of the 28.4% with thin caps, 18% had one lesion and 8% had two.

At least one non-culprit lesion with an IVUS MLA less than 4.0 mm2 was found in nearly half of all patients, which Stone said came as a surprise to researchers.

In the PROSPECT trial, after stenting of all visibly ruptured and angiographically significant lesions in patients with ACS, the investigators comprehensively characterized the left main and three major coronary arteries with IVUS and virtual histology in the majority of patients, with a slice-by-slice data linked to QCA.

Insights gained from the baseline findings include:
  • That at least one non-culprit lesion with an IVUS MLA <4.0 mm2 was identified in about 42% of patients.
  • That virtual histology thin-cap fibroatheromas were identified in the coronary tree in about 28% of patients, and were more widespread than previously described.
The trial is currently in the follow-up phase and will allow researchers to determine whether baseline demographics, biomarkers, angiography, IVUS, and virtual histology can identify patients and lesions at risk for future adverse cardiovascular events.