High-Dose Statins Reduce Plaque Volume in STEMI Patients: IBIS-4

September 02, 2014

BARCELONA, SPAIN — The use of high-dose statin therapy in STEMI patients undergoing primary PCI for an infarct-related artery significantly reduces plaque burden in the non–infarct-related coronary arteries, according to the results of the new Integrated Biomarker Imaging Study (IBIS-4)[1].

In the study, presented today here at the European Society of Cardiology 2014 Congress and published simultaneously in the European Heart Journal, the investigators report that while treatment with rosuvastatin (Crestor, AstraZeneca) 40 mg/day resulted in a regression of coronary atherosclerosis, it did not have an impact on the plaque morphology, such as changes in the necrotic core.

"The proximal segments of non–infarct-related arteries in STEMI patients feature a high atherosclerotic plaque burden, with a majority of lesions characterized by thin-cap fibroatheromas," explained lead investigator Dr Lorenz Räber (Bern University Hospital, Switzerland). "High-intensity statin therapy throughout 13 months was associated with a significant reduction in coronary atherosclerosis. However, high-intensity statin therapy did not change the proportion of necrotic core and plaque phenotypes."

Speaking with the media during a press conference, Räber said that high-intensity statins have been shown previously to regress coronary atherosclerosis in stable CHD patients. Compared with stable patients, those with acute coronary syndrome (ACS) are at a higher risk for recurrent events, he noted, and this is related to the multifocal nature of their disease and the prevalence of vulnerable plaques that extend beyond the culprit lesion. The PROVE-IT study, reported by heartwire 10 years ago, was one of the first to demonstrate the clinical benefit of using high-dose statin therapy for the reduction of recurrent events in ACS patients.

Dr Lorenz Räber

The IBIS-4 study was nested within the COMFORTABLE-AMI study and included 103 STEMI patients treated with high-dose rosuvastatin who underwent intravascular ultrasound (IVUS) and radiofrequency ultrasound (RF-IVUS) of the two non–infarct-related coronary arteries following successful primary PCI.

After 13 months, serial IVUS was available in 82 patients with 146 non–infarct-related arteries. In terms of the primary IVUS end point, the percent atheroma volume (PAV) in the non–infarct-related arteries was reduced 0.9%, a statistically significant reduction from baseline. Using RF-IVUS, the researchers reported no change in the percent necrotic core between baseline and follow-up and no improvement in lesion phenotype (no reduction in RF-IVUS–defined thin-cap fibroatheromas).

Dr Keith Fox

Dr Keith Fox (University of Edinburgh, Scotland), the moderator of the press conference, told heartwire that ACS patients should be taking a high-dose statin based on the clinical guidelines. IBIS-4, he said, is an interesting mechanistic study to determine whether that statin affects atheroma volume. "Is it impacting the thin-cap fibroatheromas?" he asked. "Not at this time. My own view is that might take longer to show that type of effect."

Also, Fox suggested that IVUS might not be sensitive enough to identify phenotypic changes in the necrotic core.

Identifying At-Risk Non–Infarct-Related Arteries

Earlier this week, the Complete Versus Lesion-Only Primary PCI Trial (CvLPRIT) showed that treating non–infarct-related arteries with PCI significantly reduced the risk of major adverse cardiac events. IBIS-4 differed from CVLPRIT in that the non–infarct-related arteries in IBIS-4 did not qualify for coronary revascularization, explained Räber.

"In the absence of angiographically significant stenosis, the plaque burden in these STEMI patients is still tremendously high," he said. As a result, IBIS-4 highlights the importance of high-dose statin therapy in ACS patients who don't appear to have significant disease when assessed by angiography.

Fox pointed to the PROSPECT study, saying that rupture often occurs in lesions not large enough to cause obstruction. "One of our real challenges in acute cardiology is identifying the lesions that are not big enough to deal with but will go on to plaque rupture and thrombosis," said Fox. In another ESC session this week, as reported by heartwire , Dr Gregg Stone (Columbia University, New York), the lead investigator of PROSPECT, said physicians need to stop relying on the angiogram. "Angiograms are terrible for telling you how severe a lesion actually is," according to Stone.

ESC spokesperson Dr Jurriën ten Berg (St Antonius Hospital, Nieuwegein, the Netherlands) said there is ample evidence showing that these STEMI patients should be treated with high-dose statin therapy. He, however, is interested in the timing of statin therapy. He told heartwire that if a high-dose statin is given to non-STEMI patients before going to the cath lab, this reduces renal insufficiency. In ACS patients, there is also a suggestion that early administration can prevent early clinical events following PCI. "If it's safe, why not give it early on?"

Dr Richard Chazal (Lee Memorial Health System, Fort Myers, FL), who was not affiliated with the study, told heartwire that while the mechanistic study failed to demonstrate a change in the composition of plaque in the non–infarct-related arteries, he suspects the mechanism of benefit might be related to inflammatory pathways. Still, the study, which demonstrated a clear reduction in plaque volume after just 13 months, is good news. STEMI patients will be treated with high-dose statins long term, so further regression of plaque in these arteries could be expected.

The study was funded by the Swiss National Science Foundation, Biosensors Europe, and Volcano. Räber is the recipient of a research fellowship funded by the Swiss National Science Foundation.

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