Author + information
- Published online July 3, 2017.
- Daisuke Nakamura, MD,
- Kunihiro Shimamura, MD,
- Davide Capodanno, MD, PhD,
- Guilherme F. Attizzani, MD,
- Massimo Fineschi, MD,
- Giuseppe Musumeci, MD,
- Ugo Limbruno, MD,
- Vasile Sirbu, MD,
- Micol Coccato, MD,
- Leonardo De Luca, MD, PhD,
- Hiram G. Bezerra, MD, PhD,
- Francesco Saia, MD, PhD and
- Giulio Guagliumi, MD∗ ()
- ↵∗Cardiovascular Department, Azienda Ospedaliera Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy
In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (p-PCI), the temporal effect of statin therapy on nonculprit lipid-rich plaques (NCLPs) is unclear. To better characterize the morphological changes of NCLP according to the intensity of statin therapy, we used serial optical coherence tomography (OCT) and a validated software that permitted semiautomated, comprehensive fibrous cap (FC) quantification at each point of its luminal boundary, with higher accuracy compared with individual measurement of arbitrary points.
This is a pre-specified analysis of the OCTAVIA (Optical Coherence Tomography Assessment of Gender Diversity in Primary Angioplasty) trial, a prospective multicenter study that evaluated the mechanisms of atherothrombosis in STEMI patients who underwent p-PCI (1). By protocol, patients underwent OCT of the infarct-related artery at baseline and at 9 months. Patients with OCT scans including the proximal and/or distal segments of implanted stents were included in the present analysis. Patients who at 9 months were on a high-dose statin regimen (defined as 80 mg/day [or 40 mg/day] of atorvastatin or 40 mg/day [or 20 mg/day] of rosuvastatin) were grouped into a high-intensity statin group, and those on <40 mg/day of atorvastatin, <20 mg/day of rosuvastatin, or different statins were grouped into a low-intensity statin group. Qualitative plaque assessment was performed by dividing each cross section into 4 quadrants and labeling each quadrant according to its most prevalent component, as follows: normal, fibrous plaque, calcified plaque, or lipid plaque. Lipid-rich plaque was defined as lipid that occupied ≥2 adjacent quadrants of the cross-sectional area, and thin-cap fibroatheroma (TCFA) was defined as lipid-rich plaque with a FC of ≤65 μm. Only nonculprit segments >10 mm in length with a FC thickness <300 μm were included in this study. Quantitative metrics of a FC covering NCLP were obtained using a semiautomated method (Figure 1) (2), and included FC thickness measured at all points on the FC boundary in all frames covering the lesion, FC surface area calculated as the product of the frame interval and arc length of the FC summed over the involved frames, and FC volume determined from cross-sectional FC surface areas in individual frames using the Simpson rule. Fractional FC surface areas were also measured based on threshold values (e.g., cap thickness <65 μm, 65 μm ≤ cap thickness <150 μm, 150 μm ≤ cap thickness <300 μm).
Overall, 108 of 140 patients in OCTAVIA fulfilled the entry criteria for the present analysis. At baseline, there were 72 NCLPs (66.7%). Of the 72 NCLPs, 33 (45.8%) were TCFAs. At follow-up, 72 patients (67%) were on a high-intensity statin regimen compared with 78 patients at baseline. Significantly greater changes in total and low-density lipoprotein cholesterol were observed in the high-intensity statin group (−1.1 ± 1.1 mmol/l [interquartile range (IQR): −44 ± 44 mg/dl] vs. −0.4 ± 1.4 mmol/l [IQR: −17 ± 53 mg/dl]; p = 0.006, and −1.2 ± 1.0 mmol/l [IQR: −45 ± 40 mg/dl] vs. −0.6 ± 1.1 mmol/l [IQR: −24 ± 41 mg/dl]; p = 0.02, respectively). Compared with baseline, there was a decrease at follow-up in the proportion of lipid plaque components (11.9% [IQR: 5.0% to 22.9%] to 8.2% [IQR: 2.5% to 16.5%; p < 0.001), length of lipid plaque (3.4 mm [IQR: 2.2 to 4.9 mm] to 2.4 mm [IQR: 1.4 to 3.8 mm]; p < 0.001), maximum lipid arc angle (134.5° [IQR: 104.0° to 190.0°] to 94.0° [IQR: 79.0° to 128.3°]; p < 0.001), FC surface area (7.4 mm2 [IQR: 4.0 to 13.7 mm2] to 3.8 mm2 [IQR: 2.1 to 7.6 mm2]; p < 0.001) and FC volume (1.4 mm3 [IQR: 0.7 to 3.0 mm3] to 0.8 mm3 [IQR: 0.5 to 1.7 mm3]; p = 0.001), whereas the minimum FC thickness was significantly increased (66.0 μm [IQR: 51.0 to 83.3 μm] to 91.5 μm [IQR: 66.0 to 122.0 μm]; p < 0.001). The proportion of TCFA decreased significantly from baseline to follow-up in the high-intensity statin group (26.4% [n = 19] vs. 9.7% [n = 7]; p = 0.002) compared with the lower-intensity group (38.9% [n = 14] vs. 25% [n = 9]; p = 0.180). In addition, the proportion of TCFA in high-intensity statin group was significantly smaller than in lower-intensity group at follow-up (9.7% [n = 7] vs. 25% [n = 9]; p < 0.001). In 20 of 33 cases (61%), TCFAs observed at baseline were converted into non-TCFAs (i.e., FC >65 μm). FC surface area <65 μm further increased in 3% of NCLPs located distally to the implanted stent, compared with 16% of NCLPs located proximally. Patients were divided into 2 groups based on the statin intensity at 9 months. Status of statin intensity was changed in 12 of 108 (11%) patients during follow-up, and this should be acknowledged as a study limitation.
In STEMI patients undergoing p-PCI, most of the untreated TCFAs along the infarct-related artery vary into a more stable phenotype after 9 months of statin therapy, particularly when higher doses are used.
Please note: Dr. Capodanno has received speaking/consulting fees from Bayer, Eli Lilly, The Medicines Company, AstraZeneca, and Abbott Vascular. Dr. Attizzani has received consulting fees from St. Jude Medical; is a proctor for Edwards Lifesciences and Medtronic; and serves on the Speakers Bureau of Abbott Vascular. Dr. Fineschi has received consulting fees/honorarium from St. Jude Medical, Boston Scientific, and AstraZeneca. Dr. Musumeci has received speaking/consulting fees from Eli Lilly, Daiichi-Sankyo, The Medicines Company, AstraZeneca, St. Jude Medical, and Abbott Vascular. Dr. Limbruno has received speaking/consulting fees from Eli Lilly, The Medicines Company, Abbott Vascular, and AstraZeneca. Dr. Sirbu has received grant support from St. Jude Medical. Dr. De Luca has received speaking/consulting fees from Eli Lilly, Daiichi-Sankyo, The Medicines Company, AstraZeneca, Bayer, Menarini, Abbott Vascular, and Boehringer Ingelheim. Dr. Bezerra has received consulting fees from St. Jude Medical. Dr. Saia has received consulting fees from Abbott Vascular, AstraZeneca, Eli Lilly, The Medicines Company, and St. Jude Medical; and has received speaking fees from AstraZeneca, Eli Lilly, Terumo, Boston Scientific, Biosensors, Terumo Menarini, Servier, and Edwards Lifesciences. Dr. Guagliumi has received consulting fees from Boston Scientific and St. Jude Medical; and has received grant support from St. Jude Medical, Boston Scientific (grant number ISROTH10105), and Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Optical Coherence Tomography Assessment of Gender Diversity in Primary Angioplasty. The OCTAVIA Trial [OCTAVIA]; NCT01377207)
- 2017 American College of Cardiology Foundation