Impact of ezetimibe on stabilization & regression of - PowerPoint PPT Presentation

Osaka National Hospital Impact of ezetimibe on stabilization & regression of intracoronary plaque as assessed by angioscopy Yasunori Ueda, MD, PhD, FACC, FESC Director, Cardiovascular Division, Osaka National Hospital President, Japanese Association of Cardioangioscopy

The Japanese Circulation Society COI Disclosure Yasunori Ueda : Remuneration for lecture: Sanofi. Scholarship fund: Abbot Vascular and Bayer. Osaka National Hospital

Process of atherosclerosis & acute MI onset From angioscopic viewpoint Angioscopy can visualize full-color real-time 4D image Osaka National Hospital

Normal Coronary Artery = No yellow plaque 1 14 1 14 2 2 13 13 3 3 12 12 LAD:1-6 LAD:1-6 LCx:7-10 LCx:7-10 64y.o. female 64y.o. female RCA:11-14 RCA:11-14 4 4 10 10 11 9 8 7 5 6 11 9 8 7 5 6 Osaka National Hospital Osaka Police Hospital

Unstable Angina = Yellow plaque & thrombus Osaka National Hospital Osaka Police Hospital

Acute Myocardial Infarction = Yellow plaque & thrombus 1 2 3 9 4 5 6 7 8 9 1 Osaka National Hospital Ueda et al. J Invasive Cardiol. 2006

Culprit of Acute Coronary Syndrome Acute MI Unstable angina Osaka National Hospital Osaka Police Hospital

Vulnerable plaque Grade 0 Grade 1 Grade 2 Grade 3 Disruption = having thrombus = rupture or erosion Incidence of plaque disruption PCI Target Lesions Non-Stenotic Yellow Plaques (%) (%) 100 † 100 * p<0.05 vs. Grade 1 * p<0.05 vs. Grade 1 † p<0.05 vs. Grade 2 † p<0.05 vs. Grade 2 80 80 . 60 60 . † * 40 40 . n=26 * n=187 20 20 . n=104 n=721 n=61 n=345 n=73 0 0 1 2 3 0 1 2 3 Yellow color grade Yellow color grade Osaka National Hospital Ueda et al. Am Heart J 2004

Acute MI in young patients (<40 yrs) N=893 Thrombogenic white lesion = Plaque erosion Yellow + Yellow – <40yrs 40–50yrs ≥50yrs Yellow+ 44% 91% 94% Smoking 88% 62% 48% Ueda et al. J Am Coll Cardiol. 2001 Osaka National Hospital Ueda et al. J Interven Cardiol, 2007

Majority of ACS is caused by yellow plaque 92.7% 94.7% 47.2% Pathologically, 30%: erosion and White 70%: rupture Yellow Angioscopically, both rupture and erosion occur at yellow plaque Acute MI Unstable AP Stable AP Osaka National Hospital Osaka Police Hospital

Ruptured plaque & Non-ruptured (erosion) plaque = Yellow plaque Non-Ruptured plaque Ruptured plaque Similar VH findings between ruptured and non-ruptured plaques Osaka National Hospital Sanidas et al. Am J Cardiol. 2011

Progression of Atherosclerosis and Acute MI Onset Plaque formation Plaque Myocardial disruption infarction Osaka National Hospital Osaka Police Hospital

Vulnerable patient = Multiple yellow plaques 12 1 12 1 11 11 7 7 1 12 1 12 8 8 2 2 9 9 11 11 2 3 2 3 10 10 4 4 Culprit lesion Culprit lesion 5 5 3 3 10 10 6 6 4 9 4 9 5 7 8 6 5 7 8 6 Osaka National Hospital Asakura and Ueda et al. J Am Coll Cardiol. 2001

Number of Yellow Plaque and Future ACS (%) Incidence of ACS events 14 12 10 NYP ≥ 2 8 p=0.02 6 4 2 NYP =0,1 0 0 1 2 3 4 5 6 7 (yrs) Follow-up period Osaka National Hospital Ohtani and Ueda et al. J Am Coll Cardiol. 2006

Number of Yellow Plaque and Future ACS Incidence of ACS events (%) 20 P=0.02 3.8-fold 15 2.2-fold 10 15.6% 9.0% 5 4.1% 0 NYP=0/1 NYP>2 NYP>5 Osaka National Hospital Ohtani and Ueda et al. J Am Coll Cardiol. 2006

Silent Plaque Disruption w/o ACS Onset Approximately Yellow Plaques 4 yellow plaques, 1 grade-3 yellow plaque and N=651 1 disrupted yellow plaque (in 165 pts) were detected per vessel. Disrupted Non-disrupted Plaques Plaques N=168 (26%) N=483 (74%) ACS Culprit Non-ACS Culprit Non-Culprit N=56 (33%) N=31 (19%) N=81 (48%) Masumura and Ueda et al. Circ J. 2010 Osaka National Hospital

From Plaque Rupture to Acute MI Onset 2 weeks later Unstable angina Osaka National Hospital Ueda et al. Herz 2003

Silent Plaque Rupture w/o ACS Onset Osaka National Hospital Osaka Police Hospital

From Plaque Rupture to Acute MI Onset Myocardial infarction Unstable angina Healed rupture Plaque disruption Osaka National Hospital Ueda et al. J Invasive Cardiol. 2006

From Plaque Formation to ACS Onset ACS Healed Thrombosis Plaque rupture +Spasm ACS Osaka National Hospital

Repeated Rupture Forms Large Plaque Burden Osaka National Hospital Burke A P et al. Circulation 2001

Time From Plaque Rupture to ACS Onset <1 day 1-5 days 211 STEMI <6hrs after onset >5 days Osaka National Hospital Rittersma S Z et al. Circulation. 2005;111:1160-1165

Time From Plaque Rupture to ACS Onset <1 day 1-5 days >5 days >5 days <1 day 1-5 days 211 STEMI <6hrs after onset Osaka National Hospital Rittersma S Z et al. Circulation. 2005;111:1160-1165

Time From Plaque Rupture to ACS Onset Silent plaque rupture Unstable angina Acute MI Thrombus formation Healed Healed ½: <24hrs ½: Days to weeks Osaka National Hospital

Determinants of ACS Onset after Plaque Rupture Plaque burden Lumen area ACS Healed Size and morphology of Blood thrombogenicity rupture Osaka National Hospital

PROSPECT study A Prospective Natural-History Study of Coronary Atherosclerosis (PROSPECT study) Event Rates for Lesions at a Median FU of 3.4 Years Osaka National Hospital Stone GW et al. N Engl J Med 2011

Highly Thrombogenic Blood in Acute MI Measured by MC-FAN Acute Myocardial Infarction Control Osaka National Hospital Matsuo and Ueda et al. Thromb Res. 2011

Highly Thrombogenic Blood in Acute MI Measured by MC-FAN BVI Blood thrombogenicity increases transiently 9000 8000 Transient increase of blood thrombogenicity in the acute phase of MI 7000 may be the cause of MI onset 6000 5000  ǂ 4000 3000 2000 1000 0 Acute Chronic Control  p<0.001 vs. Acute Myocardial Infarction ǂp<0.001 vs. Control Osaka National Hospital Matsuo and Ueda et al. Thromb Res. 2011

How to Prevent ACS Onset and How to Assess It No yellow plaque Plaque formation By lipid-lowering ? Plaque No plaque with thrombus disruption By anti-inflammation ? Occlusive No ACS event thrombus By anti-platelet/ anti-coagulation ? formation ACS Onset Osaka National Hospital

Neointima in BMS ～ Sealing effect BMS, Immediate 3 3 4 4 STENT STENT 4 4 3 3 1 1 2 1 2 1 Disrupted yellow plaque Osaka National Hospital Ueda et al. J Am Coll Cardiol. 1994

Neointima in BMS ～ Sealing effect BMS, 3 months 4 3 4 3 STENT STENT 4 4 3 3 1 1 Stent was covered 1 1 2 2 by neointima Yellow plaque was also covered by neointima Osaka National Hospital Ueda et al. J Am Coll Cardiol. 1994

Neoatherosclerosis in BMS = Yellow plaque is the cause of event BMS, 3 years BMS, 8 years Disrupted yellow plaque No yellow plaque Unstable angina No event Osaka National Hospital Osaka Police Hospital

DESNOTE study Detect the Event of very late Stent failure from the drug- eluting stent NOT well covered by nEointima determined by angioscopy Single center, prospective, follow-up study to examine if angioscopic findings (yellow color, poor neointima coverage, and thrombus) at 1 year after implantation of DES can predict the event of very late stent failure (death or MI/ UA/ revascularization at the target stent). Enrollment started in 2004. Follow up for events of very late PCI with 1Y FU with stent failure (death, DES Angioscopy MI, UA or TLR) (Enrollment) Osaka National Hospital Ueda et al. JACC Interv. 2015

DESNOTE study 1 st Endpoint vs. Osaka National Hospital Ueda et al. JACC Interv. 2015

DESNOTE study Multivariable Cox regression analysis to evaluate the risk factors of VLSF including the data at the end of follow-up Hazard ratio [95% CI] P value Presence of yellow plaque 8.55 [1.13–66.7] 0.03 Low-density lipoprotein cholesterol change from baseline to the end of follow-up 1.03 [1.01–1.04] 0.001 (mg/dL) Low-density lipoprotein cholesterol at the 0.98 [0.97–1.00] 0.07 end of follow-up (mg/dL) Stent diameter (mm) 0.28 [0.08–1.00] 0.05 Stent type (1st vs. 2nd generation), age, gender, hypertension, diabetes mellitus, current smoking, stenting for acute coronary syndrome, serum low-density lipoprotein cholesterol, serum high-density lipoprotein cholesterol, serum triglyceride, serum low-density lipoprotein cholesterol change from baseline to follow-up, serum high-density lipoprotein cholesterol change from baseline to follow-up, serum triglyceride change from baseline to follow-up, aspirin use, ticlopidin/clopidogrel use, statin use, stent diameter, total stent length, presence of yellow plaque, presence of thrombus, and minimum neointima coverage grade were included as variables. Osaka National Hospital Ueda et al. JACC Interv. 2015

Atherosclerosis in Aorta Osaka National Hospital Komatsu et al. Circ J 2015; 79 :742-750

Atherosclerosis in Aorta ４ ５ 4 3 ６ ３ 5 2 6 7 ２ ７ Osaka National Hospital By courtesy of Dr. K. Kodama.

Atheromatous embolization Ruptured plaque Plaque debris embolization Mizote and Ueda et al. Circulation. 2005 Osaka National Hospital