Six-month versus 12-month dual-antiplatelet therapy following long - - PowerPoint PPT Presentation

Six-month versus 12-month dual-antiplatelet therapy following long everolimus-eluting stent (total stent length >45mm) implantation: the IVUS-XPL randomized clinical trial

Myeong-Ki Hong, MD. PhD

• n behalf of the IVUS-XPL trial

investigators

Cardiology Division, Severance Cardiovascular Hospital and Cardiovascular Research Institute Yonsei University College of Medicine, Seoul, Korea

Potential conflicts of interest

Speaker's name: Myeong-Ki Hong  I do not have any potential conflict of interest  I have the following potential conflicts of interest to report: Honorarium: Institutional grant/research support: Consultant: Employment in industry: Owner of a healthcare company: Stockholder of a healthcare company: Other(s): 

Background

• Implanted total stent length per patient increased over

the past 20 years in daily clinical practice.

• However, long stent implantation for diffuse long

lesions still has a high risk of stent thrombosis, myocardial infarction and target-lesion failure even the use of new-generation drug-eluting stent (DES).

• Optimal dual-antiplatelet therapy strategies are not

clearly established in the era of next-generation DES.

Fokkema ML, et al, J Am Coll Cardiol 2013;61:1222-1230 Airoldi F, et al, Circulation 2007;116:745-754 Suh J, et al, JACC Cardiovasc Interv 2010;3:383-389 Naidu SS, et al, JACC Cardiovasc Interv 2012;5:626-635 Kereiakes DJ, et al, EuroIntervention 2011;7:74-83 Schulz-Schupke S, et al, Eur Heart J 2015;36:1252-1263 Gilard M, et al, J Am Coll Cardiol 2015;65:777-786 Feres F, et al, JAMA 2013;310:2510-2522 Valgimigli M, et al, Circulation 2012;125:2015-2026

Study Design of IVUS-XPL trial

• A randomized, multi-center trial at 20 centers in Korea
• Enrollment period: Oct 2010 and July 2014
• In the IVUS-XPL trial, participants (implanted everolimus-

eluting stent at target long lesion >28mm) were randomized to treatments using a 2 x 2 factorial design, IVUS use (IVUS- guidance versus angiography-guidance arm) and DAPT duration (6- versus 12-month arms). The effect of IVUS use on the clinical outcomes was previously reported (Hong SJ, Hong MK et al, JAMA 2015;314:2155-2163).

• Primary end point of this DAPT study

– The composite of cardiac death, myocardial infarction, stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding at 1 year, analyzed by intention-to-treat

61 3 33 Received clopidogrel more than 6 month Withdrew consent Lost to follow-up 699 Included in primary analysis 701 Included in primary analysis 699 Randomized to receive 6-m DAPT 13372 Patients underwent coronary angiography during the study inclusion period 11972 Excluded

1400 Randomized

18 35 8 Physicians’ discretion 4 Repeat PCI 2 Occurrence of stroke 2 Left ventricular thrombus 8 Complex lesion characteristics 2 Discretion of high-risk for ischemic events Failure to monitoring Patients’ willing to maintain clopidogrel

16 4 37 Discontinued clopidogrel during follow-up Withdrew consent Lost to follow-up

14 2 Physicians’ discretion 9 Occurrence of bleeding 2 Need of high-bleeding-risk procedure/surgery 1 Need of anticoagulation 2 Discretion of high-risk for bleeding events Patients’ willing to discontinue clopidogrel

701 Randomized to receive 12-m DAPT

Study Flow

6-month DAPT 12-month DAPT P-value

• No. of patients

699 701 Age (years), mean±SD 63±9 64±9 0.262 Male sex, No. (%) 470 (67) 494 (71) 0.192 Hypertension, No. (%) 443 (63) 455 (65) 0.550 Diabetes mellitus, No. (%) 249 (36) 257 (37) 0.686 Dyslipidemia, No. (%) 473 (68) 456 (65) 0.317 Current smoker, No. (%) 171 (25) 165 (24) 0.685 Clinical presentation, No. (%) 0.885 Stable angina 356 (51) 358 (51) Unstable angina 237 (34) 231 (33) Acute myocardial infarction 106 (15) 112 (16)

• No. of treated lesions per patients, mean±SD

1.4±0.6 1.4±0.6 0.876

• No. of stents per patients, mean±SD

1.6±0.7 1.6±0.8 0.203 Total stent length per patients (mm), mean±SD 46.5±19.7 48.2±20.2 0.107 Stent length of target long lesion (mm), mean±SD 38.6±12.5 39.8±13.0 0.066 Use of intravascular ultrasound, No. (%) 355 (51) 353 (50) 0.872

• No. of all treated lesions

944 950 Coronary arteries, No. (%) 0.744 Left anterior descending artery 518 (55) 530 (56) Left circumflex artery 187 (20) 175 (18) Right coronary artery 239 (25) 245 (26) Baseline quantitative coronary angiographic data Minimum lumen diameter (mm), mean±SD 0.84±0.44 0.84±0.43 0.877 Diameter stenosis (%), mean±SD 70.76±14.50 70.95±13.98 0.778 Lesion length (mm), mean±SD 31.7±11.7 32.4±11.9 0.237 Adjunct post-dilatation, No. (%) 614 (65) 619 (65) 0.958 Post-intervention quantitative coronary angiographic data Total stented length per lesion (mm), mean±SD 34.4±13.5 35.6±14.0 0.079 Minimum lumen diameter (mm), mean±SD 2.61±0.44 2.61±0.43 0.919 Diameter stenosis (%), mean±SD 12.71±8.19 13.19±8.87 0.251

Baseline Characteristics

6-month DAPT (n=699) 12-month DAPT (n=701) Hazard ratio (95% CI) P-value by log- rank Primary End Point The composite of cardiac death, MI, stroke, or TIMI major bleeding 15 (2.2%) 14 (2.1%) 1.07 (0.52 – 2.22) 0.854 Clinical events Death from any cause 5 (0.7%) 10 (1.5%) 0.50 (0.17 – 1.45) 0.193 Cardiac death 3 (0.4%) 5 (0.7%) 0.60 (0.14 – 2.50) 0.474 MI 1 (0.1%)

• Repeat revascularization of stented lesions

31 (4.7%) 21 (3.1%) 1.49 (0.86 – 2.59) 0.157 Repeat revascularization of target long lesions 29 (4.4%) 21 (3.1%) 1.39 (0.73 – 2.44) 0.247 The composite of cardiac death, MI, or repeat revascularization of stented lesions 35 (5.2%) 25 (3.8%) 1.40 (0.84 – 2.35) 0.193 The composite of cardiac death, target long lesion related MI, or target long lesion revascularization 33 (4.9%) 25 (3.8%) 1.32 (0.79 – 2.22) 0.290 Definite or probable stent thrombosis 2 (0.3%) 2 (0.3%) 1.00 (0.14 – 7.11) 0.999 Acute 1 (0.1%) 1 (0.1%)

• Sub-acute

1 (0.1%)

• Late

1 (0.1%)

• Stroke

6 (0.9%) 3 (0.4%) 2.00 (0.50 – 7.99) 0.318 TIMI major bleeding 5 (0.7%) 7 (1.0%) 0.71 (0.23 – 2.25) 0.563

Clinical Outcomes at 1 Year

Kaplan-Meier Curves for Primary End Point

Subgroup Analysis of the Primary End Point

• In this randomized, multicenter trial with patients who

received long-length everolimus-eluting stent implantation (mean total stent length per patient >45mm), 6-month DAPT was not associated with higher risk of the composite outcome of cardiac death, myocardial infarction, stroke and major TIMI bleeding compared to 12-month DAPT.

• Moreover, these findings were consistent in the subgroup

patients with acute coronary syndrome and with diabetes mellitus.

• This paper is accepted in J Am Coll Cardiol Interv (in

press)

Conclusions