Intravascular ultrasound (IVUS) in percutaneous coronary intervention – summary of key articles While angiography is routinely used for assessment of CAD, it is not always able to determine the clinical significance of lesions in vessels with complex anatomy such as the LM. It displays a two dimensional image of contrast-filled lumen, which does not allow an accurate assessment of plaque. This presentation describes the key studies in IVUS-guided LM interventions over the last 10 years. Prepared by Radcliffe Cardiology 21 November2016

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 POC: polygon of confluence

Clinical impact of intravascular ultrasound guidance in drug-eluting stent implantation for unprotected left main coronary disease: pooled analysis at the patient-level of 4 registries de la Torre Hernandez JM, Baz Alonso JA, Gomez Hospital JA, et al., JACC Cardiovasc Interv, 2014;7:244-54

Clinical impact of IVUS guidance in DES implantation for unprotected LM CAD de la Torre Hernandez et al, 2014 Background: Limited evidence for clinical benefit for IVUS guidance in LM disease Methods: Analysis of 4 large Spanish registries, n=1670 505 pts who had DES implantation with IVUS guidance propensity score-matched with 505 patients who received DES without IVUS guidance The role of IVUS guidance in PCI of the LM remains controversial and regulatory guidelines give only a Class IIB recommendation for the use of IVUS guidance during LM PCI.

Clinical impact of IVUS guidance in DES implantation for unprotected LM CAD de la Torre Hernandez et al, 2014 Results: At 3 year follow-up survival free of cardiac death, MI, and TLR: 88.7% vs 83.6%; p = 0.04 for IVUS vs overall population In subgroups with distal LM lesions, endpoint achieved in 90% vs 80.7%, p=0.03 Definite and probable stent thrombosis 0.6% vs 2.2%, p=0.4 IVUS-guided revascularization was identified as an independent predictor for major adverse events in the overall population (HR 0.70, 95% CI 0.52 to 0.99; p=0.04) and in the subgroup with distal lesions (HR 0.54, 95% CI 0.34 to 0.90; p=0.02).

Clinical impact of IVUS guidance in DES implantation for unprotected LM CAD de la Torre Hernandez et al, 2014

Clinical impact of IVUS guidance in DES implantation for unprotected LM CAD de la Torre Hernandez et al, 2014 Conclusions: IVUS guidance during PCI is associated with better outcomes in patients with LM disease undergoing revascularization with DES Study may not have accounted for other confounding factors in assessing the clinical benefits associated with IVUS guidance. However, it was well powered statistically

Intravascular ultrasound guidance to minimize the use of iodine contrast in percutaneous coronary intervention: the MOZART (Minimizing cOntrast utiliZation With IVUS Guidance in coRonary angioplasTy) randomized controlled trial. Mariani, J. Jr, Guedes, C., Soares, P., et al., JACC Cardiovasc Interv, 2014;7:1287–93

MOZART Study, Mariani et al, 2014 Background: Angiography uses iodine contrast agent which is associated with complications (acute kidney injury, volume overload i.e. excess fluid in blood The use of IVUS may allow reduce usage of contrast

MOZART Study, Mariani et al, 2014 Methods: 83 patients undergoing PCI randomly assigned to angiographic or IVUS guidance and all were treated by a pre-defined strategy Most had diabetes and many had long, calcified, bifurcated, and complex lesions Average follow up 4 months Clinical characteristics of patients in the two groups were similar

MOZART Study, Mariani et al, 2014 Results: IVUS group used 3 x less contrast dose compared with angiography dose (64.5 ml vs 20.0 ml) Contrast volume/creatinine clearance ratio (measure of renal function) was lower in IVUS group Procedure on average 14 minutes longer with IVUS compared with angiography (p = 0.006) No difference in clinical outcomes between two groups both in hospital and at 4 months

Volume of contrast agent used in IVUS and angiography-guided PCI MOZART Study, Mariani et al, 2014 Volume of contrast agent used in IVUS and angiography-guided PCI

MOZART Study, Mariani et al, 2014 Conclusions: The use of IVUS was associated with reduced contract use IVUS imaging should be considered for patients at high risk for contrast-induced acute kidney injury or volume overload undergoing coronary angioplasty

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;e003700.

Meta-analysis, IVUS outcomes with DES, Elgendy et al 2016 Background: 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 The mean length of the coronary lesions was 32 mm.

Meta-analysis, IVUS outcomes with DES, Elgendy et al 2016 Results: 7 RCTs including 3192 patients Mean follow-up 15 months 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)

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

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

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. This study is important because it includes only randomized controlled studies but had sufficient data to give statistically significant findings. However, the typical limitations of meta analyses were reported: lack of access to details of patient characteristics; differing definitions of MACE across studies; differing parameters measured (not all studies measured MLD pre- and post-intervention).

Effect of Intravascular Ultrasound-Guided vs Angiography-Guided Everolimus-Eluting Stent Implantation: The IVUS-XPL Randomized Clinical Trial Hong SJ, Kim BK, Shin DH, et al JAMA 2015;314:2155-63

IVUS-XPL trial, Hong et al, 2015 Background Limited clinical trial data to support the use of IVUS-guided drug eluting stent (DES) implantation. Earlier studies used 1st generation DES but 2nd generation exclusively used now.

IVUS-XPL trial, Hong et al, 2015 Methods n=1,400 Muliticentre Korean trial Randomized 1:1 to receive either IVUS-guided or angiographic-guided everolimus-eluting stent implantation Both groups were similar in terms of clinical features at the start of the study and procedures undertaken were similar

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 One-year follow-up data was available for 1,323 patients Lack of difference in ST might reflect the superior performance of everolimus-eluting stents compared with first-generation DES.

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

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 All physicians in the study were experts in both approaches, which may have biased their decisions when using angiographic guidance.