Intravascular ultrasound IVUS in the treatment of long

Intravascular ultrasound (IVUS) in the treatment of long and diffuse lesions– summary of key articles Prepared by Radcliffe Cardiology 21 November 2016

Abbreviations CABG: coronary artery bypass grafting CAD: coronary artery disease FFR: fractional flow reserve ISR: in-stent restenosis IVUS: intravascular ultrasound LAD: left anterior descending artery LCX: left circumflex artery LM: left main coronary artery MACE: major adverse cardiac events MLA: minimal lumen area MSA: minimum stent area MLD: minimal lumen diameter PCI: percutaneous coronary intervention 2 POC: polygon of confluence

Randomized comparison of clinical outcomes between intravascular ultrasound angiography-guided drug-eluting stent implantation for long coronary artery stenoses Kim, J. S. , Kang, T. S. , Mitz, G. S. , et al. , JACC Cardiovasc Interv, 2013; 6: 369 -76 3

IVUS vs angiography for long lesions, Kim et al, 2013 Background: Implantation of long stents associated with worse outcomes Data in BMS era (TULIP trial) suggests that IVUS improves outcomes in patients with long lesions Methods: • 543 patients treated with stents ≥ 28 mm randomized to IVUS guided (n = 269) or angiography guided (n = 274) DES implantation 4

IVUS vs angiography for long lesions, Kim et al, 2013 Deviations from protocol: • 13 patients (4. 8%) in the IVUS guided arm did not have IVUS guidance during PCI (reasons were patient refusal in 5, technical failure to deliver the IVUS catheter in 3, and physician decision due to severe tortuosity in 5 patients. • 41 patients (15. 0%) in the angiography-guided arm had IVUS guidance during PCI (reasons were angiographically ambiguous anatomy in 20, and operator preference in complex lesions in 21 patients). 5

IVUS vs angiography for long lesions, Kim et al, 2013 Results: At 1 year follow-up: • No difference in terms of MACE and MLD (intention to treat) • But when analysed in terms of actual treatment received (perprotocol analysis: • MLD 2. 58 vs 2. 51 mm, p = 0. 04 • MACE rates 4. 0% vs 8. 1%, p=0. 048 in IVUS vs angiography groups 6

IVUS vs angiography for long lesions, Kim et al, 2013 Intention to treat and per-protocol analysis: rates of MACE at 1 year 7

IVUS vs angiography for long lesions, Kim et al, 2013 Conclusions: • IVUS guidance during treatment of long lesions appears associated with better outcomes • Needs to be confirmed in larger studies 8

Intravascular ultrasound-guided percutaneous coronary intervention improves the clinical outcome in patients undergoing multiple overlapping drug-eluting stents implantation Ahn, S. G. , Yoon, J. , Sung, J. K. , et al. Korean Circ J, 2013; 43: 231 -8 9

IVUS in multiple overlapping DES implantation, Kim et al, 2014 Background: • IVUS guided treatment of long lesions may lead to improved clinical outcomes Methods: • Single, centre registry study, 85 consecutive patients treated with at least 64 mm multiple overlapping DES • IVUS guidance performed at operator’s discretion in 49 patients 10

IVUS in multiple overlapping DES implantation, Kim et al, 2014 Results: At 2 year follow up • Significantly lower rate of MACE (8% vs. 33. 3%, p=0. 005) • Significantly lower rate of TLR (0% vs. 27. 8%, p<0. 001) in IVUS-guided procedures vs. angiography guidance 11

IVUS in multiple overlapping DES implantation, Kim et al, 2014 Rates of MACE at 2 years 12

IVUS in multiple overlapping DES implantation, Kim et al, 2014 Conclusions: IVUS-guided implantation of multiple overlapping DES may improve outcomes in patients with long diffuse coronary lesions 13

Differential prognostic effect of intravascular ultrasound use according to implanted stent length Ahn, J. M. , Han, S. , Park, Y. K. , et al Am J Cardiol 2013; 111: 829 -35 14

IRIS-DES, Ahn et al, 2013 Background: • Aimed to discover whether IVUS guidance mitigated increased risks from long stent implantation Methods: • 3, 244 consecutive patients from IRIS-DES registry • Divided into groups according to length of implanted stent (≤ 22, 23 to 32, and ≥ 33 mm) and by IVUS use before and/or after the procedure 15

IRIS-DES, Ahn et al, 2013 Results: At 2 years follow up: • In IVUS group, no significant differences in MACE according to stent length • in the angiography group, MACE increased with increasing stent length. • In short stent length group, no statistical difference in rates of MACE between the IVUS and angiography groups, but in longer length groups differences were significant (p = 0. 57, p = 0. 009 and p=0. 006 respectively) 16

IRIS-DES, Ahn et al, 2013 Rate of MACE at 2 years 17

IRIS-DES, Ahn et al, 2013 Conclusions IVUS guidance was associated with better outcomes compared with angiography guidance when implanting long but not short DES 18

IVUS-XPL trial, Hong et al, 2015 Background • Limited clinical trial data to support the use of IVUS-guided drug eluting stent (DES) implantation in long coronary lesions Methods • n=1, 400, multicentre Korean trial • Randomized 1: 1 to receive either IVUS-guided or angiographicguided everolimus-eluting stent implantation 19

IVUS-XPL trial, Hong et al, 2015 Results • At 1 year, IVUS group had a 48% reduced risk of MACE compared with the angiography group (2. 9% vs 5. 8%, p = 0. 007) • Patients who did not meet IVUS criteria for optimum stent deployment had a significantly higher incidence of MACE compared with those who met IVUS criteria (4. 6% vs 1. 5%, p = 0. 020) • No statistically significant differences in cardiac death, target lesion–related MI, or stent thrombosis 20

IVUS-XPL trial, Hong et al, 2015 Incidence of MACE at 1 year follow up 21

IVUS-XPL trial, Hong et al, 2015 Conclusions • The use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of MACE at 1 year 22

Outcomes With Intravascular Ultrasound. Guided Stent Implantation A Meta-Analysis of Randomized Trials in the Era of Drug-Eluting Stents Elgendy, I. Y. , Mahmood, A. N. , Elgendy A. Y. , et al. Circ Cardiovasc Interv. 2016; e 003700. 23

Meta-analysis, IVUS outcomes with DES, Elgendy et al 2016 Background: 24 • When BMS were routinely used, a meta-analysis concluded that IVUS-guided stent implantation reduced MACE and target lesion revascularization • In the era of DES, does the use of IVUS still add value?

Meta-analysis, IVUS outcomes with DES, Elgendy et al 2016 Methods: • Searched for randomized studies between 2005 and February 2016 • Patients undergoing implantation of a DES randomized to either IVUS-guided or angiography-guided procedures. • Various outcome measures but all included MACE • 7 RCTs including 3192 patients 25

Meta-analysis, IVUS outcomes with DES, Elgendy et al 2016 Results: • Mean follow-up 15 months • Mean length of coronary lesion was 32 mm Post-procedure outcomes • Baseline diameter stenosis and MLD were similar in both groups (latter slightly higher with IVUS) • Postdilation more common in IVUS group (63% vs 48%, P<0. 0001) 26

Meta-analysis, IVUS outcomes with DES, Elgendy et al 2016 Results (continued) Compared with angiography, IVUS guidance is associated with: • • • 40% lower risk of MACE 40% lower risk of target lesion revascularization 54% lower risk of cardiovascular death 51% lower risk of stent thrombosis 48% lower risk of myocardial infarction* *not statistically significant 27

Meta-analysis, IVUS outcomes with DES, Elgendy et al 2016 Rate of MACE at mean 15 months follow up 28

Meta-analysis, IVUS outcomes with DES, Elgendy et al 2016 Conclusions IVUS-guided PCI is superior to angiography-guided PCI in reducing the risk of major adverse cardiac events, as well as reducing the risk of target lesion revascularization. 29

Does the Baseline Coronary Lesion Length Impact Outcomes With IVUS-Guided Percutaneous Coronary Intervention? Elgendy, I. Y. , Mahmoud, A. N. , Elgendy, A. Y. et al J Am Coll Cardiol, 2016; 68: 569 -70 30

Meta-regression analysis Elgendy et al, 2016 Methods: • Meta-regression analysis of 14 trials (7 involving DES and 7 BMS) • Baseline lesion length ranged from 8 to 35 mm (mean 25 ± 10 mm) but was longer in the DES group (32 ± 10 mm vs 13 ± 5 mm, p <0. 0001) 31

Meta-regression analysis Elgendy et al, 2016 Results: • IVUS-guided PCI was associated with a reduction in the risk of MACE (RR: 0. 70; 95% confidence interval [CI]: 0. 58 to 0. 85; p < 0. 0001) at a mean follow-up of 14 months, both in studies involving DES and BMS, with no difference in benefit between the two groups • For every 10 -mm increase in the lesion length, RR for MACE decreased by approximately 19% (p = 0. 037) 32

Meta-regression analysis Elgendy et al, 2016 Meta-regression analysis for the log risk ratio of the outcome of MACE with lesion length 33

Meta-regression analysis Elgendy et al, 2016 Conclusions: • The clinical benefit of IVUS guided procedures is greatest in longer coronary lesions • Current guidelines should be expanded to recommend IVUS guidance for PCI of longer coronary lesions (i. e. , >30 mm) 34