IBIS-4: High-Dose Statin Therapy May Reverse Atherosclerosis in STEMI

BARCELONA, Spain—High-dose rosuvastatin appears to reduce atherosclerotic burden in patients with ST-segment elevation myocardial infarction (STEMI) who have undergone successful primary percutaneous coronary intervention (PCI), according to an imaging study presented on September 2, 2014, at the European Society of Cardiology Congress and simultaneously published online in the European Heart Journal. The treatment did not, however, affect plaque composition or phenotype. 

 Lorenz Räber, MD, of Bern University Hospital (Bern, Switzerland), and colleagues looked at data from the Integrated Biomarkers and Imaging Study-4 (IBIS-4), a substudy nested within the COMFORTABLE-AMI trial of STEMI patients undergoing PCI with either the biolimus-eluting stent with a biodegradable-polymer coating (BioMatrix; Biosensors Europe SA; Morges, Switzerland) or a BMS (Gazelle; Biosensors Europe SA).
Overall, 103 patients (mean age 58.2 years; 9.7% female) at 5 centers in Switzerland and Denmark met criteria for inclusion in the substudy:
  • Age < 90 years
  • Preserved renal and liver function
  • Hemodynamic stability
  • TIMI flow ≥ 2 in the infarct-related artery after primary PCI
  • Presence of 2 non-infarct-related epicardial coronary arteries that had anatomy suitable for intracoronary imaging and were free from obstructive CAD
All patients in the substudy received rosuvastatin 20 mg/day for 2 weeks before starting on a dose of 40 mg/day for the rest of the 13-month study period. Atherosclerotic burden was assessed in the proximal segments of the arteries using IVUS and radiofrequency IVUS at baseline and 13 months; 82 patients had successful imaging at both time points.

Treatment Reduces Atherosclerosis

During the study period, average LDL cholesterol decreased from 127 to 73 mg/dL and average HDL cholesterol increased from 43 to 46 mg/dL (P < .0001 for both).

At the same time, IVUS-derived percent atheroma volume (primary endpoint) decreased by 0.93% (95% CI 0.25%-1.56%). Most patients (74%) had regression in at least 1 of the non-infarct-related arteries and 54% had regression in both.

The regression tended to be less substantial in patients with diabetes (P = .054 for interaction) and was larger in the patients with the greatest improvements in LDL and HDL cholesterol (P = .02 for both).

Rosuvastatin did not affect radiofrequency IVUS-derived percent necrotic core (secondary endpoint), which was 21.14% at baseline and 21.02% at 13 months (P = .93). However, the proportions of calcified tissue components increased (P < .0001) and fibrous tissue components decreased (P = .003).

There was no change from baseline to 13 months in the percentage of lesions that were thin-cap fibroatheromas (75.2% vs 70.3%; P = .15).

Discrepancy Between IVUS Findings and Clinical Impact 

Discussant Steven Nissen, MD, of the Cleveland Clinic (Cleveland, OH), said the study is consistent with prior larger IVUS studies looking at atherosclerosis regression with high-dose statin therapy, although it is uniquely the first in STEMI patients.

He described the plaque regression observed in all of the studies as modest, which raises the question of how high-dose statins produce large reductions in cardiovascular events with such small reductions in plaque burden. Some have proposed the “vulnerable plaque hypothesis,” which points to potential beneficial changes in plaque composition, to explain the discrepancy, Dr. Nissen said. However, he added, IBIS-4—with the lack of change in percent necrotic core and in the number of thin-cap fibroatheromas—does not provide any support to that hypothesis.

“It is my belief that the vulnerable plaque hypothesis is not based on sound science, that the reason people have events is not based necessarily on plaque composition but on many things, including platelet activation [and] inflammation…,” he said. “So focusing all of this attention on plaque may be misguided.”

But Dr. Räber was not ready to give up on the concept that changes in plaque composition could be contributing to the benefits of high-dose statins.

“My conclusion is that probably we need more highly sophisticated imaging methods to be able to detect statin-mediated alteration of the vessel wall,” he said, noting that results of an optical coherence tomography substudy are still pending.


Räber L, Taniwaki M, Zaugg S, et al. Effect of high-intensity statin therapy on atherosclerosis in non-infarct-related coronary arteries (IBIS-4): a serial intravascular ultrasonography study. Eur Heart J. 2014;Epub ahead of print.

Related Stories:

Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

Read Full Bio
  • IBIS-4 was supported by the Swiss National Science Foundation and funded by Biosensors Europe SA, the Swiss National Science Foundation, and Volcano.
  • Dr. Räber reports receiving a research fellowship from the Swiss National Science Foundation.