1. Intravascular ultrasound (IVUS) in the treatment of long and diffuse lesions– summary of key articles
Prepared by Radcliffe Cardiology
21 November2016

2. 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

3. Kim, J.S., Kang, T.S., Mitz, G.S., et al.,
Randomized comparison of clinical outcomes between intravascular ultrasound and 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
Long lesions require more aggressive stent implantations involving long stents, which have been associated with worse clinical outcomes since there is a higher risk of stent underexpansion and malapposition. While the randomized TULIP (Thrombocyte Activity Evaluation and Effects of Ultrasound Guidance in Long Intracoronary Stent Placement) trial provided the first clinical evidence that IVUS guidance when treating long lesions improves clinical outcomes, this study by Kim et al was the first randomized trial to compare IVUS-guided with angiography-guided DES implantation to in the treatment of patients with long lesions.

4. 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
In terms of procedure, both groups were similar, with a total stent length of 32.4 mm in the IVUS-guided arm and 32.3 mm in angiography-guided arm. Post-dilation was more frequently performed in the IVUS-guided arm (54.6% vs. 44.5%, p = 0.03).

5. 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).

6. 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 (per-protocol 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
Some procedures differed from the protocol (IVUS was not used in 4.8% of the IVUS group but was used in 15% of the angiography group for reasons including patient and physician preference)

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

8. 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
In addition, two different DES types were used, and any lesions requiring 2 stents (for example due to chronic total occlusion or bifurcation) was not included, meaning that these results cannot be applied to all patients with long lesions.

9. 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

10. 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

11. 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

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

13. 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

14. 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

15. 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

16. 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 = and p=0.006 respectively)

17. IRIS-DES, Ahn et al, 2013 Rate of MACE at 2 years
Despite the use of IVUS, outcomes in patients with long stent implantation remained worse than in those receiving short stents, but the risk was considerably reduced.

18. 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

19. 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 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

20. 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 = )
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 = )
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.

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

22. 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.

23. 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

24. 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?

25. 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

26. 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)

27. 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

28. 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

29. 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.
not all studies measured MLD pre- and post-intervention

30. 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

31. 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)

32. 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 < ) 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)

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

34. 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)