Objective To assess short-term and medium-term outcomes following radial and femoral artery access for primary or rescue percutaneous coronary intervention (PCI).
Design Retrospective cohort study.
Patients All 4534 patients undergoing primary or rescue PCI in Scotland between April 2000 and March 2009 using the Scottish Coronary Revascularisation Register.
Intervention Primary or rescue PCI.
Main outcome measures Procedural success; peri-procedural complications; 30-day and 1-year mortality, myocardial infarction or stroke and long-term mortality.
Results Use of the radial approach increased from no cases in 2000 to 924 (80.5%) in 2009 (p<0.001). Patients in whom the radial approach was used were more likely to be male (p=0.041) and to have multiple comorbidities (p<0.001), including hypertension (p<0.001) and left ventricular dysfunction (p<0.001). They were less likely to have renal impairment (p=0.017), multi-vessel coronary disease (p=0.001) and cardiogenic shock (p<0.001). In multivariable analyses, use of radial artery access was associated with greater procedural success (adjusted OR 1.89, 95% CI 1.26 – 2.82, p=0.002) and a lower risk of any complications (adjusted OR 0.67, 95% CI 0.51 – 0.87, p=0.001) or access site bleeding complications (adjusted OR 0.21, 0.08 – 0.56, p=0.002), as well as a lower risk of myocardial infarction (adjusted OR 0.66, 95% CI 0.51–0.87, p=0.003) or death within 30 days (adjusted OR 0.51, 95% CI 0.04 – 0.52, p<0.001). The differences in myocardial infarction and death remained significant up to 9 years of follow-up.
Conclusion Use of the radial artery for primary or rescue PCI is associated with improved clinical outcomes.
- Percutaneous coronary interventions
- myocardial infarction
- cardiac remodelling
- aortic valve disease
- intravascular ultrasound
- interventional cardiology
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- Percutaneous coronary interventions
- myocardial infarction
- cardiac remodelling
- aortic valve disease
- intravascular ultrasound
- interventional cardiology
In patients with STEMI (ST elevation myocardial infarction), primary and rescue percutaneous coronary intervention (PCI) reduce mortality and the risk of re-infarction and stroke compared with thrombolysis alone.1–3 For these reasons, primary and rescue PCI are recommended for the management of STEMI in clinical guidelines.4
Although femoral artery access is widely used for PCI,5 the radial artery is an emerging alternative. Radial artery access was introduced at the Montreal Heart Institute by Lucien Campeau and colleagues in 19646 and adopted by Kiemenij and Laarman in The Netherlands in 1993.7 Since then, radial artery access has been increasingly used by cardiologists worldwide, mainly because of perceived advantages for patient safety. Use of the femoral artery access is associated with significant access site bleeding complications,8–10 whereas use of the radial artery has comparable procedural success,11 with fewer bleeding complications,12 13 less contrast utilisation and therefore less chronic kidney injury.14 The lower bleeding risk with radial artery access is implicitly acknowledged in PCI guidelines which recommend that radial artery access should be adopted in patients at high risk of bleeding.4
Nevertheless, evidence to support using the radial artery as the access site of choice is lacking. In the RadIal Vs femorAL access for coronary intervention (RIVAL) trial,11 which is the only large multicentre clinical trial to date to compare radial versus femoral access in patients with an acute coronary syndrome, the primary outcome of death, myocardial infarction (MI), stroke and non-coronary artery bypass graft-related major bleeding at 30 days was similar in the radial (3.7%) and femoral (4.0%) groups despite only 25% of patients in the femoral group receiving a vascular closure device.15
An alternative approach to investigating the relationship between arterial access route and clinical outcomes in real world clinical practice is through cohort studies in large patient populations. In Scotland, radial access has been increasingly adopted by some operators, whereas others continue to prefer femoral access, thus providing the opportunity for a comparative study of the two approaches. Our hypothesis was that since bleeding risk16 and early mortality17 are higher in patients with STEMI than in other forms of unstable or stable coronary disease, use of radial artery access might be associated with better early and longer term outcomes compared with femoral access in this patient group.
Data sources and inclusion criteria
The Scottish Coronary Revascularisation Register prospectively collects comprehensive information on all PCI procedures in Scotland, including demographic characteristics, postcode of residence, cardiac disease severity, comorbidity, procedure details including indication, past medical and surgical history, and peri-procedural complications (http://www.scs-online.org.uk/cardreg.php). Postdischarge data are provided by linkage to the Scottish Morbidity Record (SMR1) and the General Registrar for Scotland. SMR1 routinely collects information on all admissions to acute hospitals in Scotland, including disease and procedure codes (http://www.datadictionaryadmin.scot.nhs.uk/isddd/9065.html). The General Registrar for Scotland collates death certificate data across Scotland, including cause of death. Diseases are recorded using the International Classification of Diseases and procedures using the Operating Procedure Codes. The revascularisation register is linked annually to the SMR1 and death certificate data at an individual level, providing information on fatal and non-fatal events. The most recent linkage undertaken prior to our study provided follow-up events up to March 2010.
Our cohort included all primary and rescue PCI procedures undertaken in Scotland between April 2000 and March 2009 inclusive. For patients with multiple primary or rescue PCIs within this same period, only the first procedure within the study period was included to ensure the same outcome was not attributed to multiple procedures.
A primary PCI was defined as a PCI used as the preferred reperfusion strategy following STEMI. A rescue PCI was defined as a PCI used as a second-line reperfusion strategy following failed reperfusion after thrombolysis. Radial and femoral artery access were based on the reported final access site. Elderly was defined as ≥75 years of age. Obesity was defined as a body mass index >30. Current smoking was defined as someone who regularly smoked one or more cigarettes per day and had smoked in the month preceding PCI. Socioeconomic status was measured using the Scottish Index of Multiple Deprivation (SIMD) (http://www.scotland.gov.uk/Topics/Statistics/SIMD/). The SIMD ranks data zones of residence (mean population of 750) to produce deprivation quintiles for the general population which were then applied to our study cohort using their postcode of residence. Diabetes included both type I and type II diabetes. Hypertension was defined as a systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg or use of antihypertensive therapy. Non-cardiac arteriopathy included peripheral arterial disease, previous stroke, recurrent transient ischaemic attacks and carotid stenosis ≥70%. Impaired renal function was defined as serum creatinine >200 mmol/l or use of renal replacement therapy. Impaired left ventricular function was defined as an ejection fraction of <50%. Cardiogenic shock was defined as a systolic blood pressure <90 mm Hg, pulse rate >100 bpm, and the need for inotropic drugs, intra-aortic balloon pump or cardiopulmonary support. Multiple comorbidity was defined as the presence of two or more of these conditions. Multi-vessel coronary disease was defined as having stenoses (≥75%) by visual estimation in two or more coronary arteries or the presence of left main stem stenosis. Peri-procedural outcomes were defined as events that occurred during or following the procedure, but prior to discharge from hospital, and included events both in the catheter laboratory and in the ward. Thirty-day outcomes were defined as outcomes that occurred during the procedure or up to 30 days follow-up, and included events that occurred both in hospital and post discharge. The binary outcomes studied were vascular access site bleeding, access site complication (including bleeding), any bleeding (minor, major or GI bleed), all cause death, fatal/non-fatal MI and fatal/non-fatal stroke, as well as the composite outcomes of any peri-procedural, 30-day and 1-year complication. A major bleed was defined by the use of blood products or volume replacement. Minor bleeding was defined as any clinically significant bleeding that did not qualify as major. All-cause death, fatal/non-fatal MI and fatal/non-fatal stroke were also assessed over the whole follow-up period available.
All analyses were undertaken using Stata V.11.2.18 The 9 years of data were combined to compare categorical case-mix variables in patients having either radial or femoral approach for their PCI procedure, using χ2 tests and Cuzick's non-parametric test for trend for ordinal data.19 The overall risk of adverse outcomes was compared using univariable and multivariable logistic regression models. Penalised maximum likelihood logistic regression was used where problems of data separation occurred within a model leading to a breakdown of standard binary logistic regression. We implemented the penalised method using the ‘firthlogit’ module available in Stata.20
The multivariable models were used to adjust for the potential confounding effects of age, sex, deprivation quintile, body mass index, comorbidities, smoking status, disease severity, hospital, indication for PCI (primary or rescue) and year of procedure (to adjust for unmeasured time-dependent changes resulting from greater adoption of the radial approach over time, improvements in expertise and other technological developments). In the models, we included interaction terms for access site, age group and gender to the year of procedure in order to determine whether the association between access site or age group and outcome changed over time after adjusting for the potential confounding factors listed above. The goodness of fit of the models was assessed using the area under a receiver–operator curve and Hosmer and Lemeshow's test.21
Crude survival was plotted according to the non-parametric Kaplan–Meier method. Cox proportional-hazards regression was used to determine the unadjusted and adjusted HR for survival in radial versus femoral access patients, with radial access forming the referent population. Landmark analyses were performed from day 31 to outcome or censoring.22 The landmark method of survival analysis uses a fixed time after the procedure to assess the response in different groups. This specification provides the opportunity to perform a separate statistical test to determine whether any difference in long-term outcomes is due to maintenance of short-term effects or additional effects beyond 31 days. The proportional hazard assumption was tested using a residual based inference method.23 We tested for non-linear effects of age using a natural cubic spline implemented in the ‘mvrs’ module in Stata.24
Over the 9-year period, 4606 primary or rescue PCIs were performed on 4534 patients in Scotland. Of these 4534 first procedures (2241 (49.4%) primary and 2293 (50.6%) rescue), 2142 (47.2%) were undertaken using the femoral approach and 2392 (52.8%) using the radial approach. Use of the radial approach increased from 0 (0%) cases in 2000 to 924 (80.5%) cases in 2009 (p<0.001).
Overall, 4042 (89.1%) procedures were reported as having achieved complete procedural success and a further 248 (5.5%) partial success. Complete procedure success rates were slightly better in primary compared with rescue PCI (2026 (90.4%) vs 2016 (87.9%), p=0.007). Four hundred and fifty-seven (10.0%) procedures were followed by one or more peri-procedural complications, including 45 (9.8%) vascular access site complications of which 30 (6.6%) were bleeding complications. In total, only five (0.1%) patients required platelet transfusion and eight (0.2%) patients were recorded as having had a major bleed. Bleeding was more common where the PCI was undertaken following attempted thrombolysis: 26 (1.1%) rescue versus 12 (0.5%) primary PCI. Within 30 days of the procedure, 497 (11.0%) patients had suffered an MI, 24 (0.5%) a stroke and 384 (8.5%) had died. Follow-up ranged from 0 to 3647 days, with a mean of 1231±890 days. Mean follow-up time was shorter for radial than femoral (904.0 days ±537.0 vs 1598.2±1049.0). By the end of follow-up, there were a total of 763 MIs, 113 strokes and 799 deaths.
Patients in whom the radial approach was used were more likely to be male, have comorbid conditions and left ventricular dysfunction but less likely to have renal impairment, multi-vessel coronary disease, cardiogenic shock or to have had thrombolysis administration prior to PCI (table 1). There was no significant difference in age by access route. The radial approach was associated with higher crude procedural success (complete success: 93.2% vs 86.5%, p<0.001, partial success: 7.4% vs 3.9%, p<0.001) and lower crude risk of any peri-procedural complication (6.9% vs 13.7%, p<0.001). With the radial approach, crude procedural success (complete and partial) improved over time (from 90.8% to 97.7% in 2009, p=0.007) and all complication rates fell significantly (from 13.0% to 6.0% in 2009, p=0.003). This was not seen with the femoral approach, where only the risk of bleeding fell over time (from 3.5% to 0.9%, p=0.003).
On univariable logistic regression analysis, use of the radial approach was associated with greater procedural success and a lower risk of peri-procedural complications, including access site and bleeding complications (table 2). Patients in whom radial access was used were also less likely to have suffered an MI (10.1% vs 16.7%, p<0.001) or die (5.3% vs 12.0%, p<0.001) within 30 days or by 1 year (8.6% vs 13.6%, p<0.001 and 8.0% vs 15.1%, p<0.001). All of these associations remained significant after adjustment for potential confounding factors (table 1). Removal of bleeding complications or cardiogenic shock at the time of procedure from the multivariable logistic regression had no effect on the associations or statistical significance. When stratified into primary and rescue PCI, the association between radial access and lower peri-procedural complications, MI and death within 1 year remained statistically significant (table 3).
Over the study period, there were a total of 267 deaths in the radial group and 532 in the femoral group (p<0.001). The Kaplan–Meier curves demonstrated better long-term crude survival with use of the radial approach (figure 1). The survival curves diverged over the short term but then became parallel. In the univariable Cox proportional hazards model, use of radial artery access was associated with a lower risk of MI and death over the 9 years follow-up (table 4). This association remained significant after adjustment for potential confounding factors. In the multivariable analyses, the risk of death, acute MI or stroke from 30 days onwards was similar for femoral and radial artery access (table 4). Therefore, the reduced risk of death and acute MI over 9 years follow-up associated with use of the radial approach was due to a difference in the peri-procedural and early outcomes that was maintained in the long term.
There were no significant interactions with age group, gender, procedure indication or year of procedure for peri-procedural, hospital, early or long-term outcomes. The effect of age was strictly linear for all outcomes and monotonically linear for the risk of death at 30 days and over the long term. The risk of an early complication declined with increasing age up to approximately 52 years of age before increasing monotonically with age. All models estimated were tested and found to be an adequate fit to the data.
Compared with femoral access, primary and rescue PCI undertaken using radial access had a higher rate of procedural success and a lower risk of peri-procedural, 30-day and 1-year adverse events. These findings are consistent with those of smaller, single centre studies,25 and unpublished data from the SCAAR registry in Sweden which suggest a reduced risk of adverse outcomes up to 1-year follow-up.26 In contrast to previous studies, we had data up to 9 years follow-up and were able to demonstrate that the reduced risk of adverse outcomes associated with the radial approach persisted long term.
Recruitment to randomised controlled trials is highly selected. Our study was based on a national register and, therefore, included all patients who underwent primary or rescue PCI in Scotland over the study period. The registry data are detailed and comprehensive, and are collected prospectively by clinical staff at the patient's hospital. In Scotland, data on outcomes obtained via linkage to routine hospital and death records have been shown to be as complete and accurate as that obtained using conventional follow-up methods.27 Successful linkage was achieved in 99% of cases, which is in keeping with similar studies using this registry.28 There was no evidence of a systematic bias in the successful linkage and statistical analysis confirmed no statistically significance differences according to whether or not linkage was achieved. In our study, we utilised statistical methods to adjust for differences in baseline characteristics between the approaches. However, we were not able to adjust for those variables not collected by the database (eg, door-to-balloon time and crossover rates) and so residual confounding cannot be excluded. Therefore, bystander association is a possible explanation rather than access site being causally associated with improved outcomes. This is a known limitation of all observational studies.
Sicker patients (eg, those with cardiogenic shock) were more likely to be managed using the femoral approach resulting in case selection bias. However, unlike many randomised controlled trials8 10 and the Swedish Coronary Angiography and Angioplasty Register (SCAAR) registry,26 patients with cardiogenic shock were not excluded from our study but adjusted for in the multivariable analysis. When the analyses were repeated excluding patients presenting with cardiogenic shock, mortality remained lower among those in whom the radial approach was used. In order to exclude the possibility of high-volume high experience centres resulting in systematic bias, the hospital where the procedure was undertaken was also included in the multivariable analysis.
Early bleeding events and particularly non-access site bleeding have been shown to be an independent risk factor for increased mortality.8 29 When we reran our analyses excluding patients with recorded bleeding complications, mortality remained lower in the radial approach patients. This may be due to under-recording of bleeding complications (based on clinical reporting in this study), especially non-access site and minor bleeding complications, or it may be differences in mortality being due, in part, to mechanisms other than bleeding. Complication rates in registry data are often lower than in large scale randomised controlled trials, particularly for less serious events. However, the bleeding rates in our study are consistent with other studies.8 The higher procedural success observed following radial access (which could be a reflection of operator skill) may be a factor. Use of the radial approach increased over time (with resultant increase in operator experience as demonstrated by the improved procedural success and reduced complication rates, over time) and there may have been other unmeasured changes in practice over time that impacted on outcome. However, the improved outcomes following use of the radial approach persisted after adjusting for year of procedure. In addition, there were no significant interactions with age group, gender, hospital and year of procedure suggesting that systematic changes over time were unlikely to be a source a bias. However, in contrast to the SCAAR Registry data,26 bivalirudin has not been routinely used in Scotland and therefore is not a potential confounder.
While data were not available regarding reperfusion time (call, door or ECG to balloon time) for this study, a recent meta-analysis suggested that compared with femoral artery access, radial access did not increase the time to reperfusion in acute MI patients10 and in STEMI patients in the RIVAL trial mortality was lower with radial access than with femoral access.11 In common with most observational studies, a limitation of our study was the lack of data regarding planned initial access route and crossover rate. Longer patient procedure times are associated with access site failure and crossover to femoral access has been reported to occur in 1%–10% of radial cases.10
In conclusion, the use of the radial approach in primary or rescue PCI has been increasing in Scotland, with the majority now being undertaken in this way. The radial approach appears to be associated with improved earlier and longer term clinical outcomes after adjusting for known baseline characteristics. While there will remain individual patients in whom femoral access is preferable, use of the radial approach should be actively encouraged in routine practice.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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