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High-dose statin therapy significantly reduces the lipid content of coronary atherosclerotic plaque in severely obstructive lesions in the short term, but without affecting markers of ischemic risk, according to a small pilot study.

The findings, recently presented by Annapoorna S. Kini, MD, of Mount Sinai Hospital (New York, NY), at the annual American College of Cardiology/i2 Scientific Session in Chicago, IL, raise hope that such atherosclerotic changes may contribute to plaque stabilization and potentially improved prognosis.

For the single-center YELLOW (Reduction in YELlow plaque by aggressive lipid LOWering therapy) trial, Dr. Kini and colleagues looked at 87 asymptomatic patients with multivessel disease who had undergone stenting of the target vessel and were scheduled for staged PCI of a second, obstructive lesion. The patients were randomized to receive intensive statin therapy (rosuvastatin 40 mg daily; n = 44) or standard statin care (simvistatin, atorvastatin, or rosuvastatin < 40 mg; n = 43). In all cases, the second lesion was determined to be functionally significant by fractional flow reserve (FFR ≤ 0.8).

Triple Assessment

All lesions were characterized with IVUS, FFR, and near-infrared spectroscopy at baseline and after 6 to 8 weeks of statin therapy.

At 2 months, the lipid core burden index, a grading (range 1-1,000) of the lipid composition of a vessel segment based on chemical spectra, showed an absolute reduction of 33 in the aggressive therapy arm (P = 0.0008) and no change in the standard arm (P = 0.47). The same pattern held true when shorter vessel segments with higher lipid concentrations were analyzed (for 10 mm, -118 and for 4 mm, -154; P < 0.0001 for both).

Moreover, in the aggressive therapy arm total cholesterol had declined substantially from baseline to 6 to 8 weeks (143.8 ± 26.4 mg/dL to 123 ± 27 mg/dL) as had LDL cholesterol (79.1 ± 25.3 mg/dL to 60 ± 5 mg/dL), whereas in the standard therapy arm both cholesterol values were virtually unchanged. Although C-reactive protein levels fell somewhat from baseline in the aggressive therapy arm, the reduction was not significant—probably because the inflammatory marker tends to be less prevalent in stable patients, Dr. Kini told TCTMD in a telephone interview (table 1).

Table 1. Lipid Parameters, Baseline to 6 to 8 Weeks

By contrast, over the same time frame, no differences were seen between the 2 arms in changes in morphological and functional parameters (table 2).

Table 2. IVUS/Angiographic/FFR Parameters, Baseline to 6 to 8 Weeks

 
A distinguishing feature of this study is its focus on obstructive lesions over the short term, Dr. Kini told TCTMD. “Everybody says there are changes in plaque atheroma volume [with statin therapy], but we are the first to show that what actually changes acutely is the lipid,” she observed.

More Lesion Improvement to Come?

Despite the absence of change seen in the 2-month results, Dr. Kini said she believes that over a longer period statin therapy may also promote remodeling in the rest of the plaque, potentially changing an obstructive lesion into one that is no longer functionally significant. Hints of that trend were seen in 6 patients (2 in the standard care arm and 4 in the aggressive statin arm) whose obstructions improved from measuring below to above the FFR cutpoint. As a result, she reported, these stenoses were not stented.

According to Dr. Kini, it is too early to know whether spectroscopic assessment of a lesion’s lipid core can be used to tailor patient treatment. “We are not to that level yet,” she said, “but within the next couple of years we can probably come to a decision about whether this [technology] will become a clinical tool or will stay a research tool.” 

A large randomized trial designated YELLOW II is slated to take this research to the next stage, Dr. Kini said. Not only will the new study include clinical follow-up out to 1 year but it also will assess changes in another key plaque component, the fibroatheroma cap, using optical coherence tomography, she reported, adding that a thicker cap tends to stabilize plaque, rendering it less likely to rupture. 

In a telephone interview with TCTMD, Peter H. Stone, MD, of Brigham and Women’s Hospital (Boston, MA), called the study very interesting, adding that “it may very well be important for the future.”

Meaning of Lipid Index Unclear

However, he was unclear just what the lipid core burden index represents, and said more clarification would be helpful.

“But if [the index] is a meaningful representation of the amount of lipid core within the artery wall,” Dr. Stone continued, “then these results are extremely important, showing that aggressive lipid lowering facilitates the removal of cholesterol from the arterial wall and that this removal can be quantified in vivo.”

He noted that the absence of a reduction in the degree of stenosis is potentially much less important than the reduction in lipid content. “What often leads to problems is not the magnitude of the obstruction per se but the tendency [of plaques] to become disrupted or rupture, which is typically related to the amount of lipid core and inflammation within it,” he explained.

At the moment, it is unclear whether a reduction in the lipid core should influence a decision about whether to intervene in an obstructive lesion, Dr. Stone said. “But if you can make the plaque less vulnerable to rupture or reduce its size by getting rid of some of the contents, it may limit the need to do angioplasty on each of the obstructions observed,” he added.

Dr. Stone said a study including more patients followed for a longer period that correlates plaque and clinical data would help shore up the findings. But even now the data “are very suggestive and going in the absolute right direction,” he observed. “It’s very encouraging.”

Note: Coauthors Roxana Mehran, MD, and George D. Dangas, MD, PhD, are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

  

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Source:
Kini AS. Does aggressive statin therapy reduce coronary atherosclerotic plaque lipid content? Results from: Reduction in YELlow plaque by aggressive lipid LOWering therapy (YELLOW) trial. Presented at: American College of Cardiology Scientific Session; March 25, 2012; Chicago, IL.

 

 

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