Brief, High-Dose Statin Therapy Reduces Lipid Content in Coronary Plaque
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco.
Source: Kini AS, et al. Changes in plaque lipid content after short-term, intensive versus standard statin therapy: The YELLOW Trial. J Am Coll Cardiol 2013; [Epub ahead of print].
Statin therapy has multiple beneficial effects on coronary plaque, including prevention of plaque progression and reduction in thrombotic events. It is not clear if the beneficial effect on clinical events is due to reduction in lipid content of plaque. To assess the short-term effects of intensive statin therapy on the lipid content of coronary artery plaque, Kini and colleagues performed a prospective, randomized trial in patients with multivessel coronary artery disease (CAD) wherein patients were randomized to either intensive statin therapy (rosuvastatin 40 mg daily) or standard-of-care lipid-lowering therapy. Using an innovative trial design, they studied patients with multivessel disease who were undergoing percutaneous coronary intervention (PCI) to one lesion, and had at least one other obstructive lesion (defined as fractional flow reserve [FFR] < 0.80) in another vessel. These non-target lesions (NTLs) were evaluated at baseline with FFR and intravascular ultrasound (IVUS). In addition, the authors also performed near-infrared spectroscopy (NIRS), which is an intra-arterial imaging system performed in a similar manner to IVUS, but using near-infrared light rather than ultrasound, that is able to identify lipid content within the vessel wall. Eighty-seven patients with chronic stable angina were randomized to intensive statin therapy (n = 44) or standard care (n = 43). After 6-8 weeks, repeat angiography, FFR, IVUS, and NIRS were performed at the same NTL previously imaged. These repeated measurements were performed before any additional PCI. Then, as indicated clinically, PCI was performed immediately after in lesions with FFR < 0.8. The primary endpoint was the change in lipid-core burden index at the 4 mm max segment (LCBI4mm max), wherever this occurred within the lesion.
Baseline demographics and angiographic features were similar between groups. Baseline LDL cholesterol was 82.8 ± 26.9 mg/dL in the standard therapy group and 79.1 ± 25.3 in the intensive therapy group (P = ns). Mean C-reactive protein was 1.7 and FFR was 0.73 in each group. At follow-up, median reduction in LCBI4mm max was greater in the intensive vs standard group (-149.1 [-210.9, -42.9] vs +2.4 [-36.1, 44.7]; P = 0.01). Serum LDL level in the intensive group was correspondingly lower compared to the standard therapy group (58.4 ± 26.3 vs 81.9 ± 27.9 mg/dL, respectively; P = 0.001). C-reactive protein and angiographic diameter stenosis did not change. FFR increased to > 0.8 in four patients in the intensive group and two patients in the standard group, and these patients avoided PCI. Clinical event rates were low and were not different between groups. Three patients in the intensive group required dose reduction. The authors conclude that short-term, intensive statin therapy may reduce lipid content in obstructive lesions, and these hypothesis-generating findings warrant confirmation in larger studies with longer follow-up.
This study shows that it takes just a few weeks for high-dose statins to favorably affect the lipid content in plaque. The very dynamic nature of atherosclerotic coronary plaque, and the beneficial effects of statins in the short term, are generally under-appreciated. Although this study was not powered to study clinical endpoints, it is likely that these changes will reduce the vulnerability of those plaques for progressing to acute coronary syndromes. However, the authors highlight the need for future clinical trials to confirm this. It is noteworthy that these were stable CAD patients and their average LDL was below the guideline goal of 100 mg/dL. Yet, they still derived visible benefit from intensive statin therapy. This is congruous with other studies showing the benefits of stains extend beyond simply lowering serum LDL.
This study has several strengths, including its randomized controlled design, the use of an independent data safety and monitoring board, and the use of a blinded core laboratory to analyze the imaging studies. These aspects strengthen the conclusions that can be drawn from the data. However, this was a small trial and was not powered to detect clinical endpoints. Despite these limitations, this study confirms the safety of high-dose statins in the short term, and sets the stage for larger clinical trials powered to assess hard clinical endpoints from high-dose statins in stable CAD patients.