Differences in baseline characteristics, practice patterns and clinical outcomes in contemporary coronary artery bypass grafting in the United States and Europe: insights from the SYNTAX randomized trial and registry^† Free

Abstract

OBJECTIVES

To investigate the until now undefined extent of differences in baseline characteristics, practice patterns and clinical outcomes of patients undergoing coronary artery bypass grafting (CABG) for complex coronary artery disease in the USA versus Europe.

METHODS

The impact of geographic enrolment on clinical outcomes was explored using the as-treated population of 1510 patients with de novo left main and/or three-vessel disease who underwent CABG in either the SYNTAX randomized trial or registries, and who were followed up for 5 years.

RESULTS

There were 259 (17%) patients enrolled in the USA. Patients in the USA had more comorbidities. Off-pump procedures were more frequent in the USA (32 vs 13% in Europe; P < 0.001), and crystalloid cardioplegia was used less often (17 vs 38% in Europe; P < 0.001). In the USA, more grafts per patient were used (3.1 ± 0.8 vs 2.7 ± 0.7 in Europe; P < 0.001), with less complete arterial grafting (5 vs 18% in Europe; P < 0.001) but more complete revascularization (80 vs 66% in Europe; P < 0.001). At 5-year follow-up, patients treated in the USA versus Europe had comparable rates of major adverse cardiac and cerebrovascular events (MACCEs: 28.7 vs 24.3%, respectively; P = 0.11) and the composite safety endpoint of death, stroke and myocardial infarction (MI; 15.3 vs 17.5%, respectively; P = 0.43), but a significantly higher rate of repeat revascularization (15.0 vs 9.8%, respectively; P = 0.011) driven by repeat percutaneous coronary intervention (14.6 vs 9.2%; P = 0.005) and not repeat CABG (0.4 vs 0.8%; P = 0.48). Rates of graft occlusion were significantly higher in the USA versus Europe (8.7 vs 3.2%; P < 0.001). In multivariate analysis, enrolment in the USA was a non-significant predictor of MACCE [hazard ratio (HR) = 1.31, 95% confidence interval (95% CI) 1.00–1.73; P = 0.053], but independently predicted repeat revascularization (HR = 1.66, 95% CI 1.12–2.46; P = 0.011) and graft occlusion (HR = 2.65, 95% CI 1.52–4.62; P = 0.001). It was also a non-significant predictor of reduced rates of MI (HR = 0.38, 95% CI 0.14–1.06; P = 0.064). Differences between the USA and Europe were most pronounced among patients who underwent off-pump CABG.

CONCLUSIONS

Repeat revascularization rates following CABG in the USA versus Europe were increased at 5 years, particularly in off-pump patients. There was no significant difference in the rate of death, stroke and MI.

INTRODUCTION

Randomized clinical trials are increasing in size and scope, including more patients from diverse centres and countries. Although this increases the generalizability and external validity of trial results [1], there may be differences in practice patterns that could affect the internal consistency of treatment effects. Recent interest has therefore been directed to revealing potentially clinically relevant regional and international variations [1–5].

Treatment of patients with complex coronary artery disease who require myocardial revascularization consists of both coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) [6, 7]. A great number of randomized clinical trials continue to be performed as technology improves and patient selection changes to establish current preferred revascularization strategies [8–11]. It is important to consider patient selection, procedural factors, postoperative care and strategies for follow-up, all of which can influence outcomes significantly. An important consideration has been the effect of regional variation on outcome. In a previous multivariate analysis of the SYNTAX cohort at 2-year follow-up, inclusion in the USA was a significant predictor of adverse events after CABG [12]. This may be the result of variability in practice patterns throughout geographic regions. However, a comparison of baseline characteristics, practice patterns and outcomes of patients who underwent CABG in the USA versus Europe is not available. We have therefore performed such analyses within the cohort of patients enrolled in the SYNTAX randomized trial and registry and who underwent CABG.

METHODS

Study design

The SYNTAX trial design has previously been described [12–15]. Briefly, it was a prospective, multinational randomized trial designed to test the hypothesis that PCI with drug-eluting stents was non-inferior to CABG in an all-comers population of patients with de novo left main (LM) and/or three-vessel disease. A multidisciplinary Heart Team reached consensus on whether there was expected clinical equipoise with both revascularization strategies [16]; patients were randomized in a 1 : 1 fashion to PCI (n = 903) or CABG (n = 897). If either PCI or CABG was preferred, patients were included in a CABG-ineligible PCI registry (n = 198) or PCI-ineligible CABG registry (n = 1077) [17]. A total of 649 patients of the CABG registry were randomly assigned to complete 5-year follow-up.

The institutional review board of all participating sites approved the protocol, which is consistent with the International Conference on Harmonization Guidance of Industry E6 Good Clinical Practice, the Declaration of Helsinki and all local regulations. Written consent was obtained from all participating patients before enrolment. The SYNTAX trial is registered with ClinicalTrials.gov with identifier NCT00114972.

Patients

This study included only the patients who underwent CABG, and thus presents an as-treated population of 1510 patients. In the randomized trial, 854 of the 897 patients randomized to CABG underwent CABG. There were 11 patients randomized to PCI who crossed-over and underwent CABG. Of the 649 patients included in the CABG registry, there were 644 patients who underwent CABG. One patient included in the PCI registry underwent CABG, but per protocol did not undergo 5-year follow-up.

Endpoints and definitions

The primary endpoint of this study was the composite rate of major adverse cardiac and cerebrovascular events (MACCEs) at 5 years, which included all-cause death, stroke, myocardial infarction (MI) and repeat revascularization. Secondary endpoints included the composite safety endpoint of all-cause death, stroke and MI, the individual components of MACCE, and repeat PCI, repeat CABG and graft occlusion. Definitions have been described in other reports [18, 19].

All endpoints were adjudicated by an independent Clinical Events Committee that included a neurologist.

Statistical analysis

Discrete data are presented using counts and percentages, and differences were assessed using the χ² or Fisher's exact test, where appropriate. Continuous data are reported as means ± standard deviation (SD) or medians with interquartile ranges depending on whether the data were distributed normally, which was tested using the Kolmogorov–Smirnov test. The Mann–Whitney U-test was used to compare continuous data because of sample size imbalances. Differences in event rates between the USA and Europe were explored using time-to-event Kaplan–Meier estimates with a comparison performed through Cox proportional hazard analysis. Exploratory analyses were performed for subgroups of patients in the randomized trial or nested registries, LM or three-vessel disease, and on- or off-pump and arterial or venous conduit use. Interaction terms were generated using Cox proportional hazard models. Multivariate Cox proportional hazard models were constructed to determine whether enrolment in the USA was an independent predictor of adverse events, expressed as hazard ratio (HR) with 95% confidence intervals (CIs); a backward stepwise regression with a P-value of <0.10 for entry and exit in the model was used. Pre- and intraoperative variables were entered in the model if significantly different between the USA and Europe or if believed to be clinically relevant, with forced entry of the variable of interest: age, male gender, unstable angina, pervious MI, smoking history, medically treated diabetes, hyperlipidaemia, hypertension, poor left ventricular ejection fraction, pulmonary hypertension, peripheral vascular disease, history of transient ischaemic attack or cerebrovascular accident, chronic obstructive pulmonary disease, carotid artery disease, creatinine >200 µmol/l, SYNTAX score, LM disease, enrolment in the USA, enrolment in the randomized trial (as opposed to registry), timing for treatment allocation to CABG, aprotinin given, use of crystalloid cardioplegia, the use of more than one arterial graft, incomplete revascularization and off-pump surgery. Additional separate multivariate models were constructed within patient subgroups to account for baseline and procedural differences. A two-sided P-value of <0.05 was considered to be statistically significant. Analyses were performed using SPSS Statistics version 20 software (IBM Corporation, Armonk, NY, USA).

RESULTS

Patients and baseline characteristics

Of the 1510 patients who underwent CABG in the SYNTAX randomized trial and registries, 259 (17%) patients were enrolled in the USA. The distribution of patients in the CABG arm of the randomized trial and registry was 45 and 54% in the USA, respectively (1% randomized to PCI), and 59 and 40% in Europe, respectively (1% randomized to PCI; P < 0.001).

Patients in the USA, in general, had a higher risk profile than those from Europe, with significantly increased incidences of extracardiac and cardiac risk factors, such as diabetes (30 vs 24%; P < 0.001), hypertension (85 vs 72%; P < 0.001), carotid artery disease (15 vs 9%; P = 0.006) and an urgent indication (14 vs 4%; P < 0.001) (Table 1). Only the incidence of previous MI was significantly higher in European patients (35 vs 25% in the USA; P = 0.002). The median Parsonnet score was 9 (IQR 4–14) in the USA and 6 (3–12) in Europe (P < 0.001), but the mean logistic EuroSCORE was similar (4.3 ± 4.9 vs 3.8 ± 4.3, respectively; P = 0.18).

There was a trend towards more complex lesions in Europe when compared with the USA, according to the SYNTAX score (33.1 ± 12.8 vs 31.4 ± 13.3, respectively; P = 0.066). No difference was found in the number of lesions or in the lesion characteristics. However, patients in the USA more frequently had LM disease (56 vs 40% in Europe; P < 0.001), particularly in combination with multivessel disease (Table 1). This was true for both the randomized patients (57 vs 37%, respectively; P < 0.001) and the patients included in the registries (55 vs 45%, respectively; P = 0.034).

Surgical treatment

There were several differences in procedural characteristics between Europe and the USA, which were irrespective of the presence of LM or three-vessel disease (Table 2). First of all, the time from treatment allocation to CABG was significantly longer in Europe than in the USA (6 [2–17] vs 1 [1–3] days, respectively; P < 0.001). Off-pump procedures were more frequent in the USA (32 vs 13% in Europe; P < 0.001). The use of cardioplegia differed significantly, with more use of crystalloid in Europe (38 vs 17% in the USA; P < 0.001) and blood in the USA (53 vs 45% in Europe; P = 0.054). Aprotinin was given more frequently in Europe than in the USA (39 vs 15%, respectively; P < 0.001).

In the USA, when compared with Europe, more grafts per patient were used (3 [3–4] vs 3 [2–3], respectively; P < 0.001). In particular, more venous grafts (2 [1–3] vs 1 [1–2], respectively; P < 0.001) but less arterial grafts were used (1 [1–1] vs 1 [1–2], respectively; P < 0.001); the rate of bilateral internal mammary artery use was, respectively, 10 and 25% (P < 0.001), and the radial artery was also used more frequently in Europe (9 vs 14%, respectively; P = 0.063). Therefore, more than one arterial graft was used in 17% of patients in the USA and 33% in Europe (P < 0.001); the rate of complete arterial grafting was 5 and 18% (P < 0.001), respectively. Complex grafting was more frequent in Europe than in the USA: the use of a Y-graft was 11 vs 5%, respectively; P = 0.006 and a jump-graft 36 vs 29%, respectively; P = 0.029.

The use of more grafts resulted in a higher rate of complete revascularization in the USA as opposed to Europe (80 vs 66%, respectively; P < 0.001), but also in longer procedure times (3.8 [3.2–4.5] vs 3.3 [2.8–4.0] h, respectively; P < 0.001).

Outcomes

There were no differences between the USA and Europe in clinical outcomes at 30 days (Table 3). At 5-year follow-up, the rate of MACCE was comparable between the USA and Europe (28.7 vs 24.3%, respectively; P = 0.11) (Fig. 1), as was the composite endpoint of all-cause death, stroke and MI (15.3 vs 17.5%, respectively; P = 0.43) (Fig. 1), and the rates of the individual components of all-cause death, stroke and MI (Table 3 and Fig. 1). However, patients treated in the USA had significantly higher rates of repeat revascularization (15.0 vs 9.8% in Europe; P = 0.011), which was driven entirely by repeat PCI (14.6 vs 9.2%, respectively; P = 0.005) and not repeat CABG (0.4 vs 0.8%, respectively; P = 0.48). Rates of graft occlusion were 8.7% in the USA vs 3.2% in Europe (P < 0.001).

Exploratory subgroup analyses

The difference in outcomes between the USA and Europe were irrespective of enrolment in the randomized trial or nested registries, the status of LM or three-vessel disease and the use of >1 arterial conduits (Fig. 2). However, analysis of patients who underwent on- or off-pump CABG revealed that differences between the USA and Europe were largely driven by outcome differences in off-pump procedures (Figs 2 and 3). There were no differences between the USA and Europe among patients who underwent on-pump CABG in terms of MACCE (24.7 vs 24.5%, respectively; P = 0.88) or any of the other endpoints, except for a higher rate of graft occlusion (7.1 vs 3.1%, respectively; P = 0.009). In the off-pump group, there were significant differences in MACCE between the USA and Europe (37.9 vs 22.6%, respectively; P = 0.010), as a result of higher rates of repeat revascularization and graft occlusion for patients in the USA treated off-pump (Fig. 3). Interactions were significant for MACCE (P = 0.043) and repeat revascularization (P = 0.046).

Multivariate predictors

In the multivariate model to predict MACCE, enrolment in the USA was an important predictor, but just failed to reach statistical significance (HR = 1.31, 95% CI 1.00–1.73; P = 0.053) (Table 4). It was not a significant predictor of the composite safety endpoint of all-cause death, stroke and MI, or for individual endpoints of all-cause death or stroke. However, it was an independent predictor of repeat revascularization (HR = 1.66, 95% CI 1.12–2.46; P = 0.011) and the strongest predictor of graft occlusion (HR = 2.65, 95% CI 1.52–4.62; P = 0.001). For MI, enrolment in the USA was a non-significant predictor of reduced events (HR = 0.38, 95% CI 0.14–1.06; P = 0.064).

In separate models of patient subgroups (Table 5), enrolment in the USA was only an independent predictor of MACCE in patients who underwent off-pump CABG (HR = 1.80, 95% CI 1.05–3.08; P = 0.032) (Table 5). It failed to be a predictor of the composite safety endpoint in any of the subgroups (data not shown). For repeat revascularization, enrolment in the USA remained as a significant predictor in several patient subgroups, but was strongest in the group of patients that underwent off-pump surgery and those patients who received ≤1 arterial graft. No models were constructed for any of the other endpoints.

DISCUSSION

This analysis of contemporary patients undergoing CABG within the SYNTAX trial showed that there are several important differences between the USA and Europe. First, patients in the USA present with more comorbidities. Secondly, the CABG procedure as performed in the USA is fundamentally different from Europe. Finally, long-term 5-year hard clinical outcomes of patients in the USA and Europe are comparable, but patients in the USA have significantly higher rates of repeat revascularization.

Baseline characteristics

Patients from the USA compared with those from Europe presented with a higher mean BMI and more frequently had diabetes, hypertension or renal failure. This is consistent with the health status of the general population as determined by organizations such as the International Diabetes Federation and World Health Organization, where there is a higher prevalence of diabetes and obesity and other measures of population health in the USA, irrespective of coronary artery disease, although the rate of hypertension appears lower in the USA than in Europe. The difference we found in the rate of carotid artery disease that is higher in the USA may be explained by more rigorous routine preoperative Duplex of the carotids in the USA than in Europe.

To be powered for the LM subgroup analysis, approximately 40% of patients were required to have LM disease. Enrolment of patients with three-vessel disease was quicker than those with LM disease, which resulted in an isolated inclusion of patients with LM disease at the end of enrolment. Because sites in Europe versus those in the USA finished enrolment earlier, sites in the USA were limited to inclusion of LM patients only. This may have contributed to the significantly higher rate of patients with LM disease in the USA as compared with Europe. In addition, at the time of enrolment, LM stenting was not reimbursed in the USA and could only be performed within a randomized trial. Patients with LM disease in the USA may therefore have been randomized more frequently to allow the chance for PCI. This may furthermore have caused an increase in referrals of patients with LM disease to enrolling centres. For many of these patients, however, CABG would have been the preferred strategy as determined by the Heart Team, which could explain that LM disease was also more prevalent in the USA among patients in the CABG registry.

Surgical treatment

Inclusion in the SYNTAX trial took place between March 2005 and April 2007, during which time there were clear differences in the popularity of procedures in the USA and Europe; off-pump CABG was performed more often in the USA, while arterial grafting was performed more frequently in Europe. Part of these differences may potentially be explained by patients' coronary complexity; although there were no differences between the USA and Europe in the number of lesions and there was only a marginal difference in SYNTAX scores. Indeed, there were more patients with LM disease in the USA than in Europe, but separate analyses of patients with LM and three-vessel disease showed that practice patterns differed regardless of LM disease. In addition, aprotinin was used significantly less frequently in the USA, most likely because of the negative reports associated with aprotinin use in the USA [20].

In the USA, the goal of complete revascularization appears more rigorous than in Europe. Significantly more grafts were used and more distal anastomoses per patient were performed, which indeed resulted in a higher rate of complete revascularization. Evidently, the duration of the procedure, bypass and cross-clamping time were longer as a consequence, but early safety of the procedure measured at 30 days was comparable between the USA and Europe. The postoperative stay was even significantly shorter in the USA, reflecting differences in discharge protocols among countries in Europe [21], but perhaps more similar ones for centres in the USA due to a consistent health care system.

Outcomes

The worse outcomes among patients enrolled in the USA may, in part, be explained by the higher risk profile. However, even after multivariate adjustment, the USA remained to be a (non-significant) predictor of MACCE in the final model; this was not driven by an increased risk of the composite safety endpoint of all-cause death, stroke and MI, but merely by repeat revascularizations. Moreover, there was a significantly higher rate of graft occlusions for which enrolment in the USA was the strongest of all predictors.

To a large extent, the higher rate of off-pump procedures in the USA was associated with the difference; off-pump CABG was also a non-significant predictor of repeat revascularization. Some of the differences may be explained by baseline characteristics in favour of off-pump patients in Europe (data not shown), which are similar in extent to the discrepancies in baseline characteristics of the main analysis (Table 1). Nevertheless, after adjustment for these discrepancies, enrolment in the USA remained to be a significant predictor. Moreover, in separate multivariate analyses in patient subgroups, the USA was only a significant predictor of MACCE in the subgroup of off-pump patients, suggesting that overall outcome differences between the USA and Europe are indeed largely the effect of worse outcomes in off-pump patients.

Since the USA was an important predictor of adverse events in multivariate models, we can only speculate that other factors apart from baseline and procedural characteristics have contributed as well. There might have been a more aggressive use of coronary angiography in the USA and a lower threshold for repeat revascularization, after which more patients underwent PCI of occluded vein grafts. In theory, there are a number of factors that may play a role. First, more vein grafts were used in the USA and this could be related to lower graft patency and higher repeat revascularization during follow-up. However, the interaction term of the subgroup analyses according to the use of arterial grafts remained non-significant; the impact of enrolment in the USA on outcomes did not differ in groups of patients with or without multiple arterial grafts. The variable of ‘more than one arterial graft’ furthermore failed to reach significance in any of the multivariate models. In the multivariate models within specific subgroups, enrolment in the USA was a predictor of adverse events in those patients with ≤1 arterial graft, a group that was larger in the USA than in Europe. The increasing evidence of improved outcomes with multiple arterial grafts may therefore have triggered more aggressive use of angiography in those with venous grafts, although it is unclear why this is stronger in the USA than in Europe. Secondly, strategies for follow-up may have been stricter for patients with LM disease as opposed to three-vessel disease; again this group was larger in the USA than in Europe, although our subgroup analysis did not show a significant interaction and therefore do not provide enough evidence to support this hypothesis. Finally, the report from the North American ROOBY trial of reduced graft patency after off-pump CABG may have triggered more rigorous use of angiography during follow-up after off-pump CABG in the USA [22]. There was a clear increase of repeat revascularization in patients who underwent off-pump CABG in the USA, as compared with off-pump in Europe or on-pump on either continent. As a result of the proven lack of benefit of off-pump procedures, its rate is declining: in a recent analysis of CABG surgery in the USA, the rate of off-pump was only 21% during 2009 [23]. The differences in outcomes between the USA and Europe may therefore be less apparent in current practice.

While the rate of repeat revascularization was significantly higher in the USA, the rate of MI during the follow-up was remarkably lower. It appears that the apparently closer follow-up or lower threshold to perform repeat revascularizations to some degree may prevent MI. The 2010 ESC/EACTS guidelines on myocardial revascularization do not recommend invasive testing of asymptomatic patients and the American guidelines do not provide any strategies for follow-up after revascularization [6, 7], but in light of these data, it may be required to revise recommendations to prevent MI during follow-up.

Trial design

These data offer considerations for future trial design. The significant differences in rates of repeat revascularization that cannot entirely be explained by baseline and procedural characteristics point to the fact that this endpoint may be too subjective, and comparative studies therefore may be biased when powered for the endpoint of MACCE. The composite safety endpoint of all-cause death, stroke and MI is considered to be more robust, as it includes hard endpoints. If repeat revascularization is included in the primary endpoint of a clinical trial, stratified randomization of patients from both treatment arms within the USA and Europe is necessary to ensure that differences in patient enrolment cannot be responsible for introducing a bias in the trial outcome.

Study limitations

No data on postoperative medication use were collected in patients included in the registry, and so differences between the USA and Europe in secondary prevention could not be analysed.

There was an imbalance in enrolment of patients in the USA (n = 259, 17%) and Europe (n = 1251, 83%), which may have introduced a bias in the comparison between the groups.

Pooling of data from countries within Europe was performed to achieve reasonable statistical power, while differences between practices may exist. Indeed, geographic grouping based on baseline or procedural characteristics may have generated more appropriate groups [1].

Subgroup analyses, and in particular those that are post hoc, should be interpreted with caution and as hypothesis-generating [24]. The results could be a play of chance because of low statistical power.

CONCLUSIONS

In a large contemporary cohort of patients who underwent CABG in the SYNTAX trial and registries, there were significant differences in baseline and procedural characteristics among patients included in the USA versus Europe. This resulted in significantly worse outcomes in the USA that were caused by the higher risk profile and less optimal revascularization strategies. Even with adjustment for these factors in a multivariate model, the USA remained to be an independent predictor of repeat revascularization. However, these data are hypothesis-generating and should be interpreted as such.

Funding

This study was supported by funds from Boston Scientific Corporation.

Conflict of interest: Ted E. Feldman has received consulting and lecture fees and research support from Boston Scientific Corporation and Abbott. Keith D. Dawkins owns stock in and is a full-time employee of Boston Scientific Corporation. All other authors declare that they have no conflicts of interest.

REFERENCES

APPENDIX. CONFERENCE DISCUSSION

Dr J. Boergermann(Bad Oeynhausen, Germany): I had one question about confounding, but you answered all my questions already on that point in your presentation. Second, is there any difference between the guidelines in Europe and America which might have driven the re-angiography rate? Can you speculate about this.

Dr Head: Yes, we actually looked at that. And if you first look at the US guidelines, the guidelines on CABG and also on PCI, they are actually more on the procedural aspects and not so much on what to do afterwards. So in the US guidelines, from what I've seen, there was no indication as to when to do repeat angiography in symptomatic or asymptomatic patients. If you look at the guidelines in Europe, there are some indications to do repeat angiography in patients that are symptomatic. In asymptomatic patients there is no recommendation to do this. So there are actually some differences.

Dr T. Kieser(Calgary, Alberta, Canada): This is along the same lines, and I don't mean to speak poorly of our cardiology colleagues in America, but I'm wondering, perhaps, if they're a little more trigger-happy with their PCI. I know this is anecdotal, but one of my patients was down in Montana and they cathed him for some spurious chest pain, found radial artery spasm at the beginning of the radial artery to the aorta, PCI'd it and blocked it squarely and soundly. So I think there is a difference of culture here possibly explaining this. What do you think?

Dr Head: They are more trigger-happy, indeed they'll do more repeat revascularizatons, but this may translate to hard outcomes as well. I think it's important to consider that we saw that although in the US there is more repeat revascularization, there was actually a lower rate of MI. We do not recommend doing consistent follow-up of these patients, but we may need to reconsider.

This may also be important for future trials where you look at the MACCE rate. Of course, we know that many of the trials recruit patients in the US and in Europe and MACCE rates will not be the same between the US and Europe. We may need to come back to the composite endpoint of all-cause death, stroke and MI. And actually there we may see a difference, because they do more repeat revascularization, that this will translate to lower rates of MI as well.

Dr D. Angouras(Athens, Greece): I notice that you had a little more than half of your patients that you were able to follow up for 5 years, some 600 patients, as opposed to 1100 patients registered in the CABG registry. Is this is due to financial reasons? You mentioned financial restrictions. I understand that financial restrictions are a major problem, as I come from Athens, Greece, but I would like a comment on how that effect could actually influence your final results.

Dr Head: Well, I'm quite certain it does not affect our results. If we look at the randomized trials, these patients were followed quite thoroughly. And in the CABG registry, like I said, we didn't follow all the patients. At baseline, 60% of the patients were randomized to undergo 5-year follow-up. If you look at the baseline characteristics between these groups, there are no differences between the patients that did undergo 5-year follow-up and the patients that didn't, which is what you expect because there was a randomization that took place. So I think I can say with quite some certainty that the patients that didn't undergo follow-up are very similar to the patients that did undergo follow-up and therefore I don't think it really affects our outcome here.

Dr Angouras: I guess the percentage is the same between the US and Europe?

Dr Head: Yes, it is.

Dr J. Thomas(Mumbai, India): Have you had a chance to look at the on-pump and off-pump patients in terms of repeat revascularization? Because I notice only 13% were done on off-pump in the European group whereas there were 33% in the US. In India now we are thinking about 60% being done off-pump. We don't have good follow-up data on what happened to these patients, so do you have anything on that, whether repeat revascularization was more frequent in off-pump or on-pump patients?

Dr Head: Yes, what we've seen is that repeat revascularization was particularly present in patients that underwent off-pump. This may have something to do with what is shown in some of the reports from, for example, the ROOBY trial, that there was more graft failure in patients that underwent off-pump, which could have triggered more repeat angiography and therefore more repeat revascularization as well.

Dr M. Kolowca(Rzeszow, Poland): Did you look at the composition of the populations, the American and European, and do you think it could influence the long-term result?

Dr Head: You mean the baseline characteristics of the patients?

Dr Kolowca: Yes.

Dr Head: There were some differences, indeed. But if you look at the multivariate adjustment that we did, even then the US came out as a predictor. So this is irrespective of the differences in baseline characteristics.

Author notes