Reed Miller

April 05, 2012

April 3, 2012 (Chicago, Illinois) — Aggressive lipid therapy with statins can significantly reduce the lipid content of atherosclerotic plaques in the span of a few weeks, a small imaging study suggests. The findings, say researchers, imply that statins may be able to stabilize plaques and prevent the need for secondary interventions in "staged" PCI patients.

Dr Annapoorna Kini (Mount Sinai Hospital, New York, NY) presented results from the randomized Reduction in Yellow Plaque by Aggressive Lipid Lowering Therapy (YELLOW) trial at the American College of Cardiology 2012 Scientific Sessions. Previous studies such as SATURN and STRADIVARIUS have shown that statins can cause nonobstructive coronary atheroma, as seen on intravascular ultrasound (IVUS), to regress, but the ability of statins to modulate coronary plaque composition or the flow physiology of obstructive lesions is so far unclear, Kini said, so YELLOW focused on this group.

YELLOW enrolled patients with multivessel, hemodynamically significant coronary lesions eligible for staged PCI at Mount Sinai Medical Center. After PCI of the target lesion, the remaining nontarget lesions were reevaluated with fractional flow reserve (FFR) imaging to determine whether they were hemodynamically significant. Patients with FFR <0.8 were enrolled in the study, and their lesions were imaged with gray-scale IVUS and near-infrared spectroscopy (NIRS) before being randomized to either continue with the statin they were on plus dual antiplatelet therapy or aggressive therapy with 40 mg/day of rosuvastatin. The imaging was repeated six to eight weeks later.

In the YELLOW study, the aggressively treated group showed a significant reduction in lipid-core burden index, as measured by NIRS, compared with the standard-therapy group. Usually, plaques with an FFR under 0.8 are treated with PCI, senior YELLOW investigator Dr Samin Sharma (Mount Sinai Hospital) told heartwire . "Maybe if these patients had come six or eight weeks later, they might have had a lower FFR. That is the clinical implication--that you can go very high on the statins, focused on this risk reduction," he said. "Once you take care of one vessel, the target vessel, in multivessel disease, maybe you can avoid the second or third stent procedure."

Concordant changes in conventional parameters measured by FFR and IVUS were not observed in YELLOW, but because the study results suggest that aggressive statin therapy can change a plaque's composition and stabilize it within two months, Kini et al are planning the YELLOW II study. YELLOW II will enroll many more patients and test this concept and determine whether changes in hemodynamic parameters appear over eight to nine months that allow patients to avoid PCIs.

"If you can reduce [second PCIs] by even just 50%, that would be a great, great victory," Sharma said. "Mechanistically, [YELLOW II] will be able to answer this question and, of course, see that they do not have any urgent events."

Kini receives institutional research support from InfraReDx.


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