Complex Percutaneous Coronary Intervention in Patients Unable to Undergo Coronary Artery Bypass Grafting During the COVID-19 Pandemic: Insights From the UK-ReVasc Registry

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Objectives. Cardiac surgery for coronary artery disease was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with disease ordinarily treated with coronary artery bypass grafting (CABG) instead underwent percutaneous coronary intervention (PCI). We sought to describe 12-month outcomes following PCI in patients who would typically have undergone CABG.

Methods. Between March 1, 2020 and July 31, 2020, patients who received revascularization with PCI when CABG would have been the primary choice of revascularization were enrolled in the prospective, multicenter UK-ReVasc Registry. We evaluated the following major adverse cardiovascular events at 12 months: all-cause mortality, myocardial infarction (MI), repeat revascularization, stroke, major bleeding, and stent thrombosis.

Results. A total of 215 patients were enrolled across 45 PCI centers in the United Kingdom. Twelve-month follow-up data were obtained for 97% of the cases. There were 9 deaths (4.3%), 5 MIs (2.4%), 12 repeat revascularizations (5.7%), 1 stroke (0.5%), 3 major bleeds (1.4%), and no cases of stent thrombosis. No difference in the primary endpoint was observed between patients who received complete vs incomplete revascularization (residual SYNTAX score <=8 vs > 8) (P = .22).

Conclusions. In patients with patterns of coronary disease in whom CABG would have been the primary therapeutic choice outside of the pandemic, PCI was associated with acceptable outcomes at 12 months of follow-up. Contemporary randomized trials that compare PCI to CABG in such patient cohorts may be warranted.

International guidelines advocate superiority of coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) in multivessel and left main stem disease, particularly in patients with increased anatomic complexity.^1,2 This practice is driven by clear evidence of long-term mortality benefit in those with multivessel disease³ and in those with left main disease and intermediate or high SYNTAX score.^4,5 Accordingly, such patients in whom surgical risk is not prohibitively high are seldom offered or treated with PCI.

During the first wave of the COVID-19 pandemic, access to CABG in the United Kingdom (UK) was severely limited.⁶ Many patients who would have been treated with surgical revascularization as the first choice instead underwent PCI. The UK-ReVasc Registry was a prospective, multicenter registry study established to appraise contemporary clinical outcomes following PCI in patients with coronary anatomy that would usually mandate CABG.

In-hospital and 30-day outcomes from the UK-ReVasc Registry have previously been reported, with in-hospital event rates comparable to those observed in a CABG control group.⁷ In the present study, we sought to evaluate 12-month major adverse cardiovascular events (MACE).

Study design. We conducted the UK-ReVasc registry, an investigator-initiated, multicenter, observational study at 45 sites across the UK. Lead investigators at University of Leicester and University Hospitals of Leicester (UHL) NHS Trust, in collaboration with the Robertson Center for Biostatistics at University of Glasgow, designed an online remote data entry system specific for the registry. After seeking institutional regulatory advice from the UHL Clinical Audit department, the study was registered and approved as a health survey audit and, as such, formal ethical approval was not required. Data transfer agreements utilizing fully anonymized patient data were established between UHL, University of Glasgow, and investigating sites as required.

Study participants. Participants were eligible for enrollment in the registry if they had a pattern of coronary artery disease (CAD) and would typically be considered for revascularization with CABG under normal circumstances, but who instead underwent PCI due to COVID-19 pandemic enforced cancellation of cardiac surgery services. Investigators from UK PCI centers were invited to include anonymized data on consecutive patients who met this criterion at their respective site. The study recruitment period ran from March 1, 2020 to July 31, 2020.

Data collection. Baseline demographics, clinical presentation, and reasons for not undergoing CABG were recorded. Arterial access site, anatomical distribution of CAD, SYNTAX score,⁴ and residual SYNTAX Score (rSS),⁸ as well as PCI procedural characteristics (ie, use of intravascular imaging, calcium modification, mechanical support devices) were also documented. Adjudication of coronary angiography images was undertaken by the lead investigator at each individual site. Complete revascularization was defined as intervention on all vessels larger than 2.25mm with at least 1 stenosis greater than 50%. Participating centers were asked to enter data on PCI success (defined as Thrombosis in Myocardial Infarction [TIMI] 3 flow with < 30% residual stenosis).

Outcomes. The primary outcome was a composite of all-cause mortality, myocardial infarction (MI) (defined by 4th Universal Definition of Myocardial Infarction),⁹ unplanned revascularization, and stroke. Data on hospitalization for heart failure (typical signs, symptoms, and investigation results consistent with diagnosis),¹⁰ stent thrombosis, and Bleeding Academic Research Consortium (BARC) 3-5 bleeding were also collected.¹¹

Statistical analysis. Continuous data are expressed as mean (standard deviation) or median (range), and categorical data as counts and percentages. To compare groups, an independent samples t-test was used for continuous data and chi-squared or Fisher’s exact testing for categorical data. Statistical significance was set at 0.05. Statistical analyses were performed using STATA (Version 17.0; StataCorp).

Patients. The UK-ReVasc registry enrolled 215 patients from 45 UK PCI centers. The mean age of the patients was 67 years, 34% had diabetes, 37% had LV function of 50% or less, and 75% presented with non-ST elevation acute coronary syndrome (NSTE-ACS) (Table 1). Fifty-one percent of patients had multivessel disease (MVD) with left main stem (LMS) involvement, and 45% had MVD without LMS involvement. Left anterior descending artery disease was present in 95% of the cases. The mean SYNTAX score was 28.0 (SD = 10.4) and the mean EUROSCORE II score was 2.9% (SD = 3.9).

Procedural characteristics are displayed in Table 2. In the UK-Revasc registry, 93% of the procedures were performed via the radial artery. Intravascular imaging (predominantly intravascular ultrasound) was used in 45% of the patients and calcium modification therapy (rotational atherectomy, intravascular lithotripsy, laser atherectomy) was undertaken in 24% of the patients. Mechanical support devices, both intra-aortic balloon pump, were used during 2 procedures (0.8%). Complete revascularization was achieved in 54% of the participants. PCI success was reported in 93% of the procedures.

Endpoints. Twelve-month follow-up data was obtained in 97% of the patients enrolled in the registry. The incidence of the primary endpoint in the UK-ReVasc registry patients treated with PCI was 11.0%. There were 9 deaths (4.3%), 5 MIs (2.4%), 12 repeat revascularizations (5.7%), 1 stroke (0.5%), 3 major bleeds (1.4%), and no cases of stent thrombosis (Table 3). In-hospital mortality in our UK-ReVasc registry cohort was 1.4% (3/215), compared to an EUROSCORE II score predicted in-hospital mortality following CABG of 2.9% (Fisher’s exact test, P = .39).

Results of pre-specified subgroup analyses are provided in Table 4. The use of image-guided PCI in UK-ReVasc registry patients was associated with a lower incidence of the primary endpoint (9.2% vs. 14.9%, P < .01), driven by 5 fewer repeat revascularization events compared to when intravascular imaging was not utilized. No difference in outcome was observed when the UK-ReVasc registry cohort was stratified by diabetes status.

Time-to-event analysis. A time-to-event analysis that compared complete revascularization vs incomplete revascularization in UK-ReVasc registry patients for the incidence of the primary endpoint (as defined by residual SYNTAX score thresholds of £ 8 and > 8) is displayed in the Figure. At the 12-month follow-up, the rate of event-free survival was 88% and 93% in the complete revascularization and incomplete revascularization groups, respectively (P = .22).

In this multicenter registry study that enrolled a novel cohort of higher baseline risk patients who underwent PCI instead of CABG during the COVID-19 pandemic, favorable clinical outcomes at 12-month follow-up were observed. Despite 75% acute coronary syndrome presentation and 38% experiencing reduced left ventricular ejection fraction (LVEF), our results are comparable to outcomes of lower risk patients in the PCI arms of pivotal randomized trials comparing revascularization strategies in complex CAD (Table 5). The incidence of the primary endpoint (all-cause mortality/MI/repeat revascularization/stroke) in the UK-ReVasc registry was 11%, with no adverse safety signals demonstrated.

Current guidelines recommend CABG over PCI for LMS and/or multivessel CAD with intermediate or high SYNTAX score.^1,2 Such guidance is largely based on historical randomized trials that recruited participants more than a decade ago. The pivotal Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) study demonstrated superiority of CABG vs PCI with first generation paclitaxel-eluting stents in 1800 patients with MVD or LMS, principally driven by higher rates of repeat revascularization in the PCI arm.⁴ These findings were supported by the Randomised Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Disease (BEST) study that tested second generation everolimus-eluting stents, again favoring CABG due to lower repeat revascularizations.¹² 

The 2 major randomized trials that have investigated PCI vs CABG in patients with left main stem disease report somewhat conflicting results. The Nordic-Baltic-British Left Main Revascularization Trial (NOBLE) did not meet non-inferiority for 12-month MACE when PCI was compared to CABG,⁵ while the Evaluation of XIENCE vs Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial presented data to support non-inferiority of PCI. However, EXCEL’s published results have proven controversial due to the choice of the endpoint definition for MI.¹³ In essence, both studies convey a similar message of excess spontaneous MI and repeat revascularization in those patients initially treated with PCI. Longer term follow-up of SYNTAX, BEST, and NOBLE have all indicated improved clinical outcomes with CABG.^3,14,15

Interestingly, in the SYNTAX Extended Survival 10-year follow-up cohort, mortality was significantly higher in PCI than CABG patients with multivessel disease, but not in those with left main lesions.³  Such results are highly pertinent to the current UK-ReVasc registry population because patients in SYNTAX evidently had to be deemed suitable for both forms of revascularization to be considered for randomization. More recently, the FAME-3 trial compared fractional flow reserve-guided PCI to CABG in 1500 patients and did not meet non-inferiority when compared to CABG.¹⁶ The result was driven by numerical differences in favor of CABG for all components of the primary endpoint. However, it is possible that outcomes in the FAME-3 PCI arm may have improved if intracoronary imaging was more widely employed (11.7% of FAME-3 PCI cases), since its low use in the study is perhaps not reflective of current, and certainly not best, practice in patients with complex CAD.¹⁷

The body of evidence thus far indicates that in patients amenable for either mode of revascularization, CABG is most likely to provide the greatest chance of event-free survival. However, contemporary clinical outcome data reflective of current interventional cardiology practice are lacking. While surgical techniques have no doubt improved, interventional cardiologists now more commonly utilize intravascular imaging to guide and optimize PCI strategy, since this is associated with a reduction in all-cause mortality, cardiovascular death, and adverse events as demonstrated by an 18 000 patient meta-analysis.¹⁸ Furthermore, potent anti-platelet agents, novel stent technologies, and refinement of left main stem strategies have reduced the risk of stent failure and subsequent ischemic events.^19,20

The establishment of the UK-ReVasc registry afforded a unique opportunity to observe practice and outcomes in a cohort of patients denied access to CABG because of the COVID-19 pandemic.⁷ Such patients with complex CAD and of low surgical risk (EUROSCORE II = 2.9%) are rarely treated outside of randomized trials because CABG is now well established as the default mode of revascularization in this group. The elevated risk profile of our UK-ReVasc registry cohort is highlighted when compared with data from PCI arms of pivotal randomized controlled trials, such as SYNTAX, BEST, and FAME-3 (Table 5).^4,12,16Our cohort is older, with more complex disease and a higher incidence of reduced LVEF and unstable presentation. These factors are associated with increased mortality risk, and reduced LVEF is a well-established independent predictor of poorer prognosis, in particular.²¹

Outcomes following surgical revascularization have improved over recent years, and, in the recent FAME-3 trial, were very good indeed. The FAME-3 CABG arm MACE rate of 6.9% compares favorably to the 12% incidence reported in the SYNTAX trial for the identical composite endpoint of death, MI, stroke, and repeat revascularization.^4,16 Such significant improvements in event-free survival following CABG have been described over time, in part due to higher rates of off-pump CABG, increased use of blood cardioplegia, and improvements in guideline-directed medical therapy.²²

While outcomes from FAME-3 are not directly comparable to our UK-ReVasc registry cohort given the marked differences in baseline demographics, it does indicate that a high bar has been set for PCI to achieve clinical equipoise in this patient group. It is notable that the markedly higher rate of repeat revascularization required in PCI patients from prior studies was not reproduced in our UK-ReVasc patients when compared with the FAME-3 CABG cohort (UK-ReVasc: 5.7% vs FAME-3 CABG: 3.9%).  However, despite a 4-fold higher rate of intravascular imaging use (44.8%) in the UK-ReVasc registry as compared with the PCI arm of FAME-3 (11.7%), a similar incidence of repeat revascularization procedures was noted (UK-ReVasc: 5.7% vs FAME-3 PCI: 5.9%) even though our patient population was of higher baseline risk and had greater anatomical complexity.

Subgroup analysis of the UK-ReVasc registry patients suggests that intravascular imaging use was associated with a significant reduction (9.2% vs 14.9%) in the incidence of the primary endpoint. This is a hypothesis-generating result and supports findings of large, randomized data sets that conclude that intravascular imaging can be used as a strategy to guide PCI results in lower rates of target vessel failure and repeat revascularization.²³ 

A further subanalysis of event-free survival stratified by residual SYNTAX score demonstrated no difference between those UK-ReVasc registry patients who received complete revascularization as defined by the residual SYNTAX score (rSS <=8) vs those who received incomplete revascularization (rSS > 8). However, this was limited by the small sample size and relatively short follow-up period, as benefits from more complete revascularization in the PCI cohort of the original SYNTAX trial were principally observed at 5 years.²⁴

To address the potential flaws of prior studies that have compared CABG vs PCI in this patient population, especially in relation to systematic intracoronary imaging, calcium modification, and other advances in contemporary revascularization, a further randomized trial may be required to best inform contemporary practice. However, this is of course with the caveat that, in these rapidly evolving fields, by the time any such a trial reports, techniques may have further advanced, limiting the contemporaneity and pertinence of the results. 

Limitations. First, the data collected are observational and subject to selection bias at each individual center. The number of patients enrolled at each center was low and may suggest such bias, however, the study was undertaken during the first wave of the COVID-19 pandemic when elective coronary angiography was essentially cancelled in the UK and a 40% reduction of patients with ACS attending hospital was observed.²⁵This may in part explain the low enrollment. Second, all cases were investigator-reported and not centrally adjudicated. However, all centers are familiar with systematic data collection for national British Interventional Cardiovascular Society audit purposes and should be considered accurate. Third, our registry is relatively small with few clinical events. However, a very low number of patients were lost to follow-up, therefore these data provide an accurate representation of contemporary UK PCI practice in complex CAD patients. Fourth, our secondary analyses do not take all potential confounding factors into account and thus should only be interpreted in that context.

In patients with patterns of coronary disease in whom CABG would have been the primary therapeutic choice outside of the pandemic, PCI was associated with acceptable outcomes at 12-month follow-up. Contemporary randomized trials that compare PCI to CABG in such patient cohorts may be warranted.

From the ¹Department of Cardiovascular Sciences and the NIHR Leicester Biomedical Research Center, Glenfield Hospital, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK; ²College of Medicine, Swansea University, Morriston Regional Heart Center, Swansea, UK; ³Department of Cardiology, Royal Victoria Hospital, Belfast, UK; ⁴West of Scotland Heart and Lung Center, Golden Jubilee National Hospital, Glasgow, UK; ⁵Leeds General Infirmary, Leeds, UK; ⁶Dorset Heart Center, Royal Bournemouth Hospital, Bournemouth, UK; ⁷Worcestershire Royal Hospital, Worcester, UK; ⁸BHF Center of Research Excellence and NIHR Biomedical Research Center at King’s College London, UK; Guy’s and St Thomas’ Hospital NHS Foundation Trust, UK; ⁹Barts Heart Center St Bartholomew's Hospital, Barts and the London School of Medicine and Dentistry, London, UK; ¹⁰Liverpool Heart and Chest Hospital, Liverpool, UK; ¹¹Department of Cardiology, Royal Papworth Hospital, Cambridge, UK; ¹²Freeman Hospital, Newcastle University, Translational and Clinical Research Institute, Newcastle-Upon-Tyne, UK; ¹³Salisbury NHS Foundation Trust, Salisbury, UK; ¹⁴Oxford Heart Center, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; ¹⁵Portsmouth Hospitals University NHS Trust, Portsmouth, UK; ¹⁶Department of Cardiology, King's College NHS Foundation Trust, London, UK; ¹⁷Department of Cardiology, Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital, Sheffield, UK; ¹⁸Robertson Center for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK; ¹⁹Faculty of Medicine, University of Southampton & Wessex Cardiac Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK; ²⁰BHF Glasgow Cardiovascular Research Center, University of Glasgow, UK; Golden Jubilee National Hospital, Clydebank, UK.

Acknowledgments: The authors acknowledge the support of the National Institute of Health Research Biomedical Research Center in Leicester.

Funding: This study received in-kind data management support from the Robertson Center for Biostatistics at The University of Glasgow.

Disclosures: The authors report no financial relationships or conflicts of interest regarding the content herein.

Address for correspondence: Thomas A. Kite, Department of Cardiovascular Sciences and the NIHR Leicester Biomedical Research Center, Glenfield Hospital, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, LE3 9QP, UK. Email: tom.kite@nhs.net; X: @aladwiniec

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