Transradial Versus Transfemoral Intervention for the Treatment of Left Main Coronary Bifurcations: Results From the COBIS (COronary BIfurcation Stenting) II Registry

Abstract: Objectives. We compared clinical outcomes of transradial (TR) and transfemoral (TF) percutaneous coronary interventions (PCI) in patients with left main coronary artery (LMCA) bifurcation lesions. Background. The use of TR approach is growing as an alternative to the routine use of the TF approach. However, there are limited data comparing the outcomes of these two approaches for the treatment of LMCA bifurcation lesions. Methods. Between January 2003 and December 2009, a total of 853 patients undergoing PCI using drug-eluting stent (DES) implantation for LMCA bifurcation lesions were enrolled from 18 centers in Korea. We classified patients into the TR group (n = 212) and TF group (n = 641) according to the vascular approach. The primary outcome was major adverse cardiac event (MACE) rate, including composite of cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR) in all patients and in 483 propensity-score matched patients. Results. There were no significant differences between TR and TF approaches for procedural success in the main vessel (98.6% vs 99.7%; P=.07) and side branches (90.6% vs 94.4%; P=.05). Thrombolysis in Myocardial Infarction major or minor bleeding occurred less frequently in the TR group than in the TF group (2.4% vs 9.4%; P=.01). Over a median follow-up of 35 months, MACE rate did not significantly differ between TR and TF groups (9.9% vs 14.5%; adjusted hazard ratio, 0.80; 95% confidence interval, 0.49-1.29; P=.36). These results were consistent after propensity-score matched analysis. Conclusions. TR-PCI is a safe and effective vascular approach even in patients with LMCA bifurcation lesions undergoing PCI with DES implantation.

J INVASIVE CARDIOL 2015;27(1):35-40
Key words: left main coronary artery, bifurcation, percutaneous coronary intervention, transradial approach

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Left main coronary artery (LMCA) bifurcation lesions remain challenging because of technical complexity and usually require the transfemoral (TF) approach due to practical limitations, such as the need for guide catheter support and equipment size restrictions, associated with transradial (TR) percutaneous coronary intervention (PCI) in high-risk lesion anatomy.¹ Compared with TF access, the TR approach can significantly reduce bleeding complications and improve clinical outcomes.^2,3 Thus, the TR approach is increasingly recognized as an alternative to the routine use of the TF approach.^4-6 However, due to practical, patient, and technical problems, the implementation of TR-PCI has remained limited in more complex coronary lesion subsets, such as LMCA bifurcation lesions. Therefore, we compared the efficacy and safety of TR and TF approaches on procedural success, bleeding complications, and clinical outcomes in patients with LMCA bifurcation lesions.

Methods

Study population. This study was conducted based on the Coronary Bifurcation Stenting (COBIS) II registry. The COBIS II registry is a retrospective multicenter registry of patients with coronary bifurcation lesions who underwent PCI with drug-eluting stent (DES) implantation. From January 2003 through December 2009, a total of 2897 patients were enrolled from 18 major coronary intervention centers in Korea. The inclusion criteria were: (1) coronary bifurcation lesions treated solely with at least 1 DES; and (2) a main-vessel diameter of ≥2.5 mm and a side-branch diameter of ≥2.3 mm confirmed by core lab quantitative coronary analysis. Exclusion criteria were: (1) cardiogenic shock or experience of cardiopulmonary resuscitation; and (2) protected left main disease. Among 2897 patients, a total of 853 patients had LMCA bifurcation lesions. The registry was sponsored by the Korean Society of Interventional Cardiology. The local institutional review board at each participating hospital approved this study and waived the requirement for informed consent for access to each institutional PCI registry.

Percutaneous coronary intervention. Access, type of DES, and use of intravascular ultrasound (IVUS) or glycoprotein IIb/IIIa receptor inhibitors were at the operator’s discretion. Decisions to treat bifurcation lesions by the provisional strategy or elective SB stenting were made by individual operators. Duration of dual-antiplatelet therapy was also at the operator’s discretion. All patients were administered loading doses of aspirin (300 mg) and clopidogrel (300-600 mg) before PCI, unless they had previously received these antiplatelet medications. Coronary angiography and stent implantation were performed using standard interventional techniques.⁷

Patient follow-up. Demographic, clinical, angiographic, procedural, and outcome data were collected with the use of a web-based reporting system. Additional information was obtained by further inquiries into medical records or telephone contact if necessary. All baseline and procedural cine coronary angiograms were reviewed and qualitatively analyzed at the angiographic core laboratory in the Cardiac and Vascular Center, Samsung Medical Center in Seoul, Korea.

Definition and study endpoints. Baseline bifurcation anatomy was assessed according to the Medina classification.⁸ Medina type (1, 1, 1), (1, 0, 1), and (0, 1, 1) lesions were defined as true bifurcation lesions. Angiographic success was defined as the achievement of a Thrombolysis in Myocardial Infarction (TIMI) flow grade of III with a final residual stenosis of <30% for the main vessel or <50% for the side branch by visual estimation. Procedural success was defined as angiographic success without in-hospital death, myocardial infarction (MI), or emergent coronary artery bypass graft (CABG) surgery. The periprocedural period included the first 48 hours after PCI. Periprocedural complications were defined as the occurrence of coronary arterial dissection or abrupt closure during PCI, cardiac death, emergent CABG, coronary perforation, intracranial bleeding, or cardiac tamponade during PCI. Death that could not be attributed to non-cardiac etiology was considered cardiac death. MI was diagnosed by electrocardiographic changes and/or a rise and fall of cardiac biomarkers in the presence of ischemic symptoms that were not related to the index procedure during follow-up. Target lesion revascularization (TLR) was defined as any repeated PCI or CABG to treat a luminal re-narrowing in-stent or within a 5 mm border adjacent to the stent. Stent thrombosis was adjudicated according to Academic Research Consortium definitions as definite, probable, or possible.⁹ Bleeding events were evaluated during hospitalization and characterized according to TIMI study criteria (TIMI major, TIMI minor bleeding).¹⁰ Additionally, the amount of bleeding was measured by changes in hemoglobin or hematocrit before and after intervention.

The primary objective of our study was to compare long-term major adverse cardiac event (MACE) rate between patients treated by TR and TF approaches. MACE was defined as the occurrence of cardiac death, MI, and TLR in-hospital and during follow-up. The secondary objectives included procedural success, periprocedural complications, and bleeding complications.

Statistical analysis. Comparisons for continuous variables were made using the t-test or Wilcoxon rank-sum test when applicable. Categorical data were tested using the chi-squared test. Survival curves were constructed using Kaplan-Meier estimates and compared with the log-rank test. The Cox proportional hazard model was used to compare the risks of adverse cardiac events between TR and TF groups. The propensity scores were estimated using multiple logistic regression analysis. A full non-parsimonious model was developed that included age, sex, diabetes, hypertension, dyslipidemia, smoking, peripheral artery occlusive disease, chronic renal failure (CRF), cerebrovascular accident, previous MI, previous PCI, left ventricular ejection fraction (LVEF), multivessel coronary artery disease (CAD), other bifurcation treatment, other PCI, bifurcation type by Medina classification, bifurcation angle, stenting technique, final kissing ballooning (FKB), IVUS guidance, stent type, and maximal stent diameter in Tables 1 and 2. The discrimination and calibration ability of the propensity-score model were assessed by means of the c-statistic and the Hosmer-Lemeshow statistic. Cox regression analysis using pairs matched by a greedy algorithm and the nearest available pair-matching method among patients with an individual propensity score was also performed to evaluate the reduction in outcome risk. The covariate balance achieved by matching was assessed by calculating the absolute standardized differences in covariates between the TR and TF groups. An absolute standardized difference of <10% for the measured covariate suggests appropriate balance between the groups. In the propensity-score matched population, continuous variables were compared with a paired t-test or the Wilcoxon signed-rank test, as appropriate, and categorical variables were compared with the McNemar’s or Bowker’s test of symmetry, as appropriate, while the reduction in the risk of outcome was compared by use of the stratified Cox regression model with prognostic covariates, as the combination of regression adjustment in matched samples generally produces the least biased estimate. Cumulative incidence rates of individual clinical outcomes and composite outcomes were estimated by the Kaplan-Meier method and compared by the paired Prentice-Wilcoxon test. Statistical analyses were performed with SAS 9.² (SAS Institute, Inc). All tests were two-tailed and P<.05 was considered statistically significant.

Results

Baseline characteristics

Overall population. Among 2897 patients, a total of 853 patients had LMCA bifurcation lesions. TR-PCI was performed in 201 patients (24.9%) and TF-PCI was performed in 641 patients (75.1%). Baseline clinical characteristics are represented in Table 1. Overall, patients in the TR group were less likely to have dyslipidemia and CRF, and to present with acute coronary syndrome (ACS). However, patients in the TR group were more likely to have a reduced LVEF (<50%) compared with those in the TF group. Angiographic and procedural characteristics are shown in Table 2. The patients in the TR group were less likely to have multivessel CAD and true bifurcation lesions. The rates of IVUS guidance, use of double-stent technique, and FKB were significantly higher in patients treated with the TF approach.

Propensity-matched population. After performing propensity-score matching for the entire population, a total of 161 matched triplets of patients were created (Tables 1 and 2). The c-statistic for the propensity score model was 0.761, which indicates good discrimination (Hosmer-Lemeshow goodness of fit, P=.66). There were no significant differences in the baseline clinical, angiographic, and procedural characteristics for the propensity-matched subjects except for reduced LVEF, guiding catheter size, and stent technique.

Procedural and clinical outcomes

Overall population. The overall procedural success rates were high, and were similar between the two approaches (Table 3). The difference between the two groups in the occurrence of periprocedural complications was not statistically significant. Median follow-up duration of the overall patients was 1038 days (interquartile range, 747-1498 days). There was no significant difference in the follow-up duration between TR and TF groups (median, 1071 days vs 1028 days; P=.58). There were no significant differences in MACE rates (Figure 1A and Table 4), and cardiac death or MI (Table 4). However, TLR occurred less frequently in the TR group than in the TF group (Table 4).

Propensity-matched population. The procedural success rates and periprocedural complication rates were similar between the two groups. There were also no significant differences in MACE rates (Figure 1B and Table 4), and cardiac death or MI (Table 4). However, the TLR rate in the TR group was significantly lower than in the TF group (Table 4).

Bleeding events

Overall population. When bleeding events were characterized according to TIMI study criteria, TIMI major or minor bleeding occurred less frequently in the TR group than in the TF group (Table 3). Moreover, the amount of bleeding measured by changes in hemoglobin was significantly less in the TR group than in the TF group (Table 3).

Propensity-matched population. TIMI major or minor bleeding occurred less frequently in the TR group than in the TF group. Bleeding measured by changes in hemoglobin was significantly less in the TR group than in the TF group (Table 3).

Discussion

In the present study, we compared the efficacy and safety of the TR and TF approaches on procedural success, bleeding complications, and clinical outcomes in patients with LMCA bifurcation lesions using data from a large-scale, observational, multicenter registry in Korea. The salient findings of this study are as follows: (1) TR-PCI, compared with TF-PCI for LMCA bifurcation lesions, had similar long-term clinical outcomes in all populations and propensity-score matched populations except the incidence of TLR. (2) TLR rates of the TR group were lower compared with the TF group after propensity-score matching with covariate adjustment. (3) TR-PCI was associated with reduced bleeding and the procedural success rate of TR-PCI was not inferior to TF-PCI.

Procedural success. Unlike a previous meta-analysis,4 recent clinical trials demonstrate no differences in procedural success between vascular approach strategies for coronary intervention.^11,12 Despite the concerns about the technical challenges of guiding catheter support, limitations of catheter size, and the potential need for multiple angioplasty catheters or mechanical hemodynamic support devices, TR-PCI for LMCA is associated with similar procedural success compared with TF-PCI.^1,13,14 Even though there are limitations to TR-PCI, procedural success rates in our study were similar between the two vascular approach methods, showing the feasibility of TR-PCI for LMCA bifurcation lesions.

Although radial artery size generally limits the arterial sheath to 6 Fr, advances in PCI devices, eg, the increased inner diameter of guiding catheters combined with the decreased profile of balloons and stents, have allowed bifurcation procedures through radial access.¹⁵ Moreover, similar procedural success rates may be attributed in part to techniques, such as provisional single stenting, that are now regarded as standard techniques for most bifurcation PCIs and are feasible through radial 6 Fr access, high stent deployment pressure, FKB, and the use of IVUS guidance, which are not excluded by a TR approach.^16,17

Bleeding complications and clinical outcomes. Both TR-PCI and TF-PCI for LMCA bifurcation lesions had favorable long-term clinical outcomes in our study. This result is consistent with a recent report that showed that TR-PCI for unprotected LMCA disease was feasible and associated with similar procedural success, abbreviated hospitalization, reduced bleeding, and comparable late-term clinical safety and efficacy.1 Moreover, our results do not differ from those of larger comparative studies that established the relationship between TR-PCI and decreased early- and late-term mortality.^3,18 However, TLR rates of the TR group were lower than those of the TF group after propensity-score matching with covariate adjustment. The mechanism of this finding is unclear. One possible explanation is that even after propensity-score matching, there were significant differences in stent technique between the two groups, and that more frequent use of crush, culotte, and kissing-stent techniques in the TF group might affect higher TLR rates.

Bleeding complications after PCI are associated with increased risk of post-PCI morbidity and mortality.^12,19-21 In the present study, bleeding amounts measured by hemoglobin changes before and after PCI were lower in the TR group than in the TF group. In addition, TIMI major or minor bleeding occurred less frequently in the TR group than in the TF group in our study. These findings may contribute to the numerically lower MACE rate in the TR group than in the TF group in the present study.

Study limitations. We recognize that our study has several limitations. First, comparisons to this analysis are limited by its non-randomized and retrospective design, in which operator bias and unmeasured confounders may preclude any definite conclusions, despite multivariable adjustment. Patients were selected to undergo TF or TR approach on the basis of patient, procedural, and likely also institutional/operational factors. As a result, sicker patients with more complex anatomy were selected to undergo TF intervention. We tried to overcome this limitation through propensity-score matching analysis. Second, we did not have data describing procedure duration, contrast volume, fluoroscopic time, length of hospital stay, or data for the numbers or ratio of crossover between the TR group and TF group due to technical reasons. By way of example, crossover from TR to TF vascular approach is one of the important determining factors of procedural success during challenging PCI. Third, data about the administration of glycoprotein IIb/IIIa inhibitor were lacking. A greater number of patients in the TF group presented with ACS in our study, which potentially caused glycoprotein IIb/IIIa inhibitors to be used more frequently.

Conclusion

The present study showed that TR-PCI might be superior to TF-PCI in reducing bleeding complications and is associated with similar procedural success rates, and comparable long-term clinical outcomes in patients with LMCA bifurcation lesion. Based on these results, the TR approach might be considered as the first access site for treatment of LMCA bifurcation lesions.

References

1. Yang YJ, Kandzari DE, Gao Z, et al. Transradial versus transfemoral method of percutaneous coronary revascularization for unprotected left main coronary artery disease: comparison of procedural and late-term outcomes. JACC Cardiovasc Interv. 2010;3(10):1035-1042.
2. Montalescot G, Ongen Z, Guindy R, et al. Predictors of outcome in patients undergoing PCI. Results of the RIVIERA study. Int J Cardiol. 2008;129(3):379-387.
3. Chase AJ, Fretz EB, Warburton WP, et al. Association of the arterial access site at angioplasty with transfusion and mortality: the MORTAL study (Mortality benefit Of Reduced Transfusion after percutaneous coronary intervention via the Arm or Leg). Heart. 2008;94(8):1019-1025.
4. Agostoni P, Biondi-Zoccai GG, de Benedictis ML, et al. Radial versus femoral approach for percutaneous coronary diagnostic and interventional procedures: systematic overview and meta-analysis of randomized trials. J Am Coll Cardiol. 2004;44(2):349-356.
5. Hamon M, Rasmussen LH, Manoukian SV, et al. Choice of arterial access site and outcomes in patients with acute coronary syndromes managed with an early invasive strategy: the ACUITY trial. EuroIntervention. 2009;5(1):115-120.
6. Jolly SS, Amlani S, Hamon M, Yusuf S, Mehta SR. Radial versus femoral access for coronary angiography or intervention and the impact on major bleeding and ischemic events: a systematic review and meta-analysis of randomized trials. Am Heart J. 2009;157(1):132-140.
7. Jo HS, Park JS, Sohn JW, et al. Culprit-lesion only versus multivessel revascularization using drug-eluting stents in patients with ST-segment elevation myocardial infarction: a Korean acute myocardial infarction registry-based analysis. Korean Circ J. 2011;41(12):718-725.
8. Medina A, Suarez de Lezo J, Pan M. [A new classification of coronary bifurcation lesions]. Rev Esp Cardiol. 2006;59(2):183.
9. Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007;115(17):2344-2351.
10. Chesebro JH, Knatterud G, Roberts R, et al. Thrombolysis in Myocardial Infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation. 1987;76(1):142-154.
11. Jolly SS, Yusuf S, Cairns J, et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet. 2011;377(9775):1409-1420.
12. Romagnoli E, Biondi-Zoccai G, Sciahbasi A, et al. Radial versus femoral randomized investigation in ST-segment elevation acute coronary syndrome: the RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) study. J Am Coll Cardiol. 2012;60(24):2481-2489.
13. Hsueh SK, Hsieh YK, Wu CJ, et al. Immediate results of percutaneous coronary intervention for unprotected left main coronary artery stenoses: transradial versus transfemoral approach. Chang Gung Med J. 2008;31(2):190-200.
14. Bertrand OF, Bagur R, Costerousse O, Rodes-Cabau J. Transradial vs femoral percutaneous coronary intervention for left main disease in octogenarians. Indian Heart J. 2010;62(3):234-237.
15. Caputo RP, Tremmel JA, Rao S, et al. Transradial arterial access for coronary and peripheral procedures: executive summary by the Transradial Committee of the SCAI. Catheter Cardiovasc Interv. 2011;78(6):823-839.
16. Palmerini T, Marzocchi A, Tamburino C, et al. Impact of bifurcation technique on 2-year clinical outcomes in 773 patients with distal unprotected left main coronary artery stenosis treated with drug-eluting stents. Circ Cardiovasc Interv. 2008;1(3):185-192.
17. Kim JS, Hong MK, Ko YG, et al. Impact of intravascular ultrasound guidance on long-term clinical outcomes in patients treated with drug-eluting stent for bifurcation lesions: data from a Korean multicenter bifurcation registry. Am Heart J. 2011;161(1):180-187.
18. Sciahbasi A, Pristipino C, Ambrosio G, et al. Arterial access-site related outcomes of patients undergoing invasive coronary procedures for acute coronary syndromes (from the ComPaRison of Early Invasive and Conservative Treatment in Patients With Non-ST-ElevatiOn Acute Coronary Syndromes [PRESTO-ACS] Vascular Substudy). Am J Cardiol. 2009;103(6):796-800.
19. Rao SV, Eikelboom JA, Granger CB, Harrington RA, Califf RM, Bassand JP. Bleeding and blood transfusion issues in patients with non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2007;28(10):1193-1204.
20. Doyle BJ, Rihal CS, Gastineau DA, Holmes DR Jr. Bleeding, blood transfusion, and increased mortality after percutaneous coronary intervention: implications for contemporary practice. J Am Coll Cardiol. 2009;53(22):2019-2027.
21. Mehta SR, Jolly SS, Cairns J, et al. Effects of radial versus femoral artery access in patients with acute coronary syndromes with or without ST-segment elevation. J Am Coll Cardiol. 2012;60(24):2490-2499.

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From the 1Samsung Medical Center, Sungkyunkwan University School of Medicine; 2Yonsei Cardiovascular Center, Yonsei University College of Medicine; 3Wonju Christian Hospital; 4Department of Cardiology, Ajou University School of Medicine; and 5The Catholic University of Korea College of Medicine.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted March 27, 2014 and accepted May 12, 2014.

Address for correspondence: Associate Professor Seung-Hyuk Choi, Sungkyunkwan University, Cardiology, 50 Irwon-Dong, Gangnam-Gu, Seoul, 135-710, South Korea. Email: sh1214.choi@samsung.com