The radial approach during percutaneous coronary intervention (PCI) has been reported to reduce the incidence of bleeding complications. However, the radial approach still accounts for <10% of procedures worldwide and only 1% in the United States. Our objective was to compare the effect of radial versus femoral vascular access on the time to reperfusion, incidence of bleeding complications, and overall clinical outcomes in the setting of primary PCI. We prospectively collected data on all patients undergoing primary PCI at the Montreal Heart Institute from April 1, 2007 to March 30, 2008. The time to revascularization and major bleeding were prespecified as a co-primary end point, and major adverse cardiac events, including death, myocardial infarction, and target vessel revascularization within 12 months, were considered a secondary end point. A total of 489 patients were included in the present longitudinal cohort study, 234 in the femoral group and 254 in the radial group. In the propensity-adjusted model, the use of the femoral approach was a strong independent predictor of bleeding (odds ratio 4.22, 95% confidence interval 3.17 to 10.60). No significant difference between the radial and femoral groups was observed relative to the time to revascularization (21.4 ± 11.8 minutes vs 22.8 ± 10.3 minutes, respectively; p = 0.68). Moreover, the radial approach was associated with a decreased risk of major adverse cardiac events (odds ratio 0.31, 95% confidence interval 0.10 to 0.94). In conclusion, primary PCI using the radial approach was associated with a fourfold reduction in major bleeding, without compromising the time to revascularization. Moreover, the radial approach was associated with a significant reduction in major adverse cardiac events at 12 months.
Studies have highlighted the pivotal role of primary percutaneous coronary intervention (PCI) in reducing mortality, as well as diminishing reinfarction and stroke to an even greater extent. Current practice guidelines consider primary PCI the preferred reperfusion strategy for patients presenting with ST-segment elevation myocardial infarction (STEMI), conditional on the timely performance of the PCI procedure. Periprocedural bleeding remains a major limitation of primary PCI because of the need to administer potent antithrombotic agents. Previous data have established the strong association between major bleeding after PCI and increased mortality. Substantial efforts have been made to reduce the occurrence of periprocedural bleeding, from using vascular closure devices to the use of antithrombotic agents associated with a lower bleeding risk. Radial access during PCI has emerged as a promising alternative to femoral access.
We hypothesized that the radial approach would be associated with a reduction in major bleeding complications without increasing the time to reperfusion of the infarct-related artery. Therefore, the aim of our study was to compare the effect of radial versus femoral access during primary PCI on the time to reperfusion, incidence of bleeding complications, and 1-year clinical outcomes after STEMI.
Methods
We performed a longitudinal cohort study that enrolled all patients undergoing primary PCI at a high-volume, tertiary, North American academic medical center from April 1, 2007 to March 30, 2008. The data were prospectively collected in a registry implemented in conjunction with a protocol-driven clinical care program to monitor the clinical complications related to procedures performed in the cardiac catheterization laboratories at the Montreal Heart Institute. The inclusion criteria for the prospective registry were age >18 years and the diagnosis of STEMI within 12 hours of symptom onset (thoracic pain for >30 minutes not responding to nitroglycerine, with ST-segment elevation >1 mm in ≥2 contiguous leads). We excluded patients receiving fibrinolytic therapy. Also, in our series, none of the patients had received either bivalirudin or enoxaparin before PCI.
The patients were included in the radial or femoral group according to the initial intended vascular approach. The selection of the radial or femoral approach as the initial access strategy was left to the discretion of the interventional cardiologist; the radial approach is the default strategy at the Montreal Heart Institute catheterization laboratories. In accordance with institutional policy, the femoral approach was favored for patients with negative findings on the Allen test and for patients with a mammary coronary bypass graft.
The institutional review board of the Montreal Heart Institute approved the study. All subjects provided written informed consent for the collection of patient data for academic and research purposes.
For the radial group, the Allen test was performed routinely before puncture to evaluate the collateral flow between the radial and ulnar arteries. PCI was performed using 6Fr guiding catheters. At procedure completion, the sheath was removed immediately, and a compression bracelet was installed for 3 hours. In the femoral group, PCI was performed using 6Fr guiding catheters. At the end of the procedure, an iliofemoral angiogram was obtained, and a vascular closure device (AngioSeal, St. Jude Medical, St. Paul, Minnesota, or Perclose, Abbott Vascular Devices, Redwood City, California) was deployed on confirmation of suitable vascular anatomy and a proper vascular entry site. When the use of such devices was contraindicated, the sheath was removed 4 to 5 hours after the procedure, and manual compression was performed for a minimum of 15 minutes or until satisfactory hemostasis had been achieved. This was followed by placement of a compressive bandage for 6 hours.
All patients received 325 mg of aspirin and either 300 or 600 mg of clopidogrel before primary PCI. A bolus of unfractionated heparin (70 UI/kg) was administered before the procedure if the patient had come directly from our emergency room; otherwise, anticoagulation was adjusted according to the periprocedural active clotting time results. The treating interventionalist decided whether to use abciximab; when used, a bolus of 0.25 mg/kg was given either before or during PCI. The active clotting time was titrated to achieve a value of >300 seconds in patients receiving heparin without abciximab and >250 seconds in patients receiving both.
The patients were assigned to the radial or femoral group according to the initial intended access site. All patients were analyzed on an intention-to-treat basis. Access was considered successful once the sheath was inserted into the artery.
Because we sought to determine whether the radial approach was associated with a reduction in major bleeding complications without increasing the time to revascularization, our prespecified primary composite end point was the time to revascularization and the incidence of major bleeding. The time to revascularization was defined as the interval between the arrival of the patient in the catheterization laboratory to the first attempt to open the artery, by aspiration thrombectomy, balloon inflation, or direct stenting. Additional documented key intervals were the time to access (interval between the arrival of the patient and successful insertion of the arterial sheath), door-to-balloon time (interval from the first hospital arrival to the first attempt at opening the artery), and total ischemia time (interval between symptom onset and the first attempt at opening the artery). In accordance with The Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) bleeding definition, we considered major bleeding as the cumulative 7-day postprocedural occurrence of intracranial or intraocular bleeding, access site hemorrhage requiring intervention, hematoma with a diameter of ≥5 cm, a reduction in hemoglobin level of ≥4 g/dl without an overt bleeding source or ≥3 g/dl with an overt bleeding source, reoperation for bleeding, or transfusion of a blood product.
Our secondary end point was major adverse cardiac events (MACE) occurring within 12 months after PCI. MACE was defined by any of the following events: cardiac death, myocardial infarction, or target vessel revascularization. In-hospital events were recorded by the research nurses trained in clinical data acquisition, and the patients were followed up after discharge at 30 days and 1 year, by either clinical visits or telephone interview. All end points were adjudicated by 2 independent reviewers who were not involved in the data collection or analysis (PC and MC), with contentious cases submitted to a third reviewer (DA) for final adjudication.
Data are expressed as the mean ± SD for continuous, normally distributed variables. Categorical variables are expressed using numbers and percentages. Continuous variables were compared using the Student t test for normally distributed variables and the nonparametric Mann-Whitney U statistical test for non-normally distributed variables. Categorical variables were compared using the chi-square test or Fisher’s exact test when the expected value of the cells was <5. Multivariate binary logistic regression analysis was performed to assess the association between the vascular access site and bleeding, and the selection of variables for the final multivariate model was done with a backward stepwise algorithm (gender, vasculopathy, previous coronary artery bypass graft, Killip class III-IV, hypertension, heparin, clopidogrel, aspirin, antiglycoprotein IIb/IIIa, intra-aortic balloon pump, age, body mass index, hemoglobin, and maximum activating clotting time). The results are reported as odds ratio with the associated 95% confidence intervals. Because of the nonrandomized nature of our study group assignment, propensity score analysis was used to determine the likelihood of undergoing radial vascular access for each patient using nonparsimonious logistic regression analysis. The latter model was constructed with radial access as the dependent variable, with the following variables included in the model (as well as significant interactions): age, gender, previous peripheral vascular disease, previous myocardial infarction, previous coronary artery bypass graft, previous cerebrovascular accident, diabetes mellitus, Killip class III-IV, use of an intra-aortic balloon pump, anterior myocardial infarction, creatinine, Thrombolysis In Myocardial Infarction flow after the procedure, door-to-balloon time, and ejection fraction. All p values are 2-sided and were considered statistically significant at p <0.05. Data were analyzed using the Statistical Package for Social Sciences, version 16, software (SPSS, Chicago, Illinois). All authors had full access to, and take full responsibility for, the integrity of the data, and all have read and agree to the manuscript as written.
Results
From April 2007 to April 2008, 530 patients with STEMI were included in the registry. Of these patients, 41 were excluded: 28 because of previous treatment with fibrinolytic therapy and 13 because of late presentation (>12 hours) after symptom onset. The clinical characteristics of the study cohort are listed in Table 1 .
| Variable | Radial (n = 238) | Femoral (n = 251) | p Value |
|---|---|---|---|
| Age (years) | 58.7 ± 12.6 | 64.2 ± 13.1 | <0.0001 |
| Men | 192 (80.7%) | 147 (58.6%) | <0.0001 |
| Hypertension | 102 (42.9%) | 134 (53.4%) | 0.02 |
| Diabetes mellitus | 30 (12.6%) | 47 (18.7%) | NS |
| Hyperlipidemia ⁎ | 100 (42%) | 127 (50.6%) | NS |
| Smokers | 104 (43.7%) | 103 (41%) | NS |
| Body mass index (kg/m 2 ) | 28.1 ± 4.9 | 26.1 ± 4.7 | 0.008 |
| Previous myocardial infarction | 25 (10.5%) | 48 (19.1%) | 0.008 |
| Peripheral vascular disease | 11 (4.6%) | 24 (9.6%) | 0.04 |
| Cerebrovascular disease | 7 (3%) | 12 (4.8%) | NS |
| Previous coronary artery bypass graft | 0 | 26 (10.4%) | <0.0001 |
| Anterior myocardial infarction | 127 (55.9%) | 129 (53.8%) | NS |
| Killip class III-IV | 5 (2.1%) | 30 (12%) | <0.0001 |
| Ejection fraction (%) | 49.5 ± 9.4 | 45 ± 12.1 | 0.002 |
| ST-segment deviation (mm) | 12.1 ± 6.5 | 13.2 ± 9.2 | NS |
| ST-segment resolution (mm) | 2.7 ± 2.7 | 3.7 ± 3.5 | 0.004 |
| Troponin peak (UI/dl) | 7.5 ± 22.3 | 15 ± 52.6 | NS |
| Creatine kinase-MB fraction (UI/dl) | 161.9 ± 144.9 | 183.6 ± 165.1 | NS |
| Creatinine (μmol/L) | 83.5 ± 36.4 | 86.2 ± 28.9 | NS |
| Glucose (mg/dl) | 84 ± 33 | 92 ± 48 | NS |
| Hemoglobin (g/dl) | 140.7 ± 15.8 | 134 ± 21 | <0.0001 |
⁎ Total cholesterol level 200 mg/dl and/or low-density lipoprotein level 130 mg/dl, or using lipid-lowering therapy.
Patients undergoing radial catheterization were younger, were more often men, and had a greater body mass index. In contrast, hypertension, peripheral vascular disease, previous myocardial infarction, previous coronary artery bypass graft, and Killip class III-IV at presentation were significantly more frequent in the femoral access group.
The procedural characteristics are listed in Table 2 . The crossover rate from the radial to femoral approach was 10.1%; the crossover rate from femoral to radial was only 1.2%. In the radial group, 87.4% of patients received optimal antithrombotic therapy (aspirin, clopidogrel, heparin, and glycoprotein IIb/IIIa inhibitors) compared to 69.6% in the femoral group (p <0.001). Greater procedural success rates, defined as an improvement in Thrombolysis In Myocardial Infarction flow after PCI, were observed in the radial group than in the femoral group, with Thrombolysis In Myocardial Infarction flow grade 3 after PCI documented in 94.5% versus 88.4% (p = 0.04), respectively.
| Variable | Radial (n = 238) | Femoral (n = 251) | p Value |
|---|---|---|---|
| Crossover to femoral/radial | 24 (10.1%) | 3 (1.2%) | <0.0001 |
| Culprit coronary artery | 0.005 | ||
| Left main | 2 (0.9%) | 4 (1.6%) | |
| Left anterior descending | 97 (41.8%) | 94 (38.2%) | |
| Left circumflex | 34 (14.7%) | 39 (15.9%) | |
| Right | 99 (42.7%) | 95 (38.6%) | |
| Graft | 0 | 14 (5.7%) | |
| Number of narrowed coronary arteries | 0.01 | ||
| 1 | 191 (80.3%) | 177 (70.5%) | |
| 2 | 36 (15.1%) | 47 (18.7%) | |
| 3 | 11 (4.6%) | 27 (10.8%) | |
| Optimal antithrombotic treatment ⁎ | 208 (87.4%) | 174 (69.6%) | <0.0001 |
| Aspirin | 236 (99.2%) | 237 (94.4%) | 0.003 |
| Clopidogrel | 231 (97.1%) | 222 (87.4%) | <0.0001 |
| Glycoprotein IIb/IIIa inhibitors | 217 (91.2%) | 181 (72.1%) | <0.0001 |
| Unfractionated heparin | 235 (98.7%) | 240 (95.6%) | NS |
| Maximum active clotting time (s) | 284.9 ± 63 | 285.3 ± 80.9 | NS |
| Initial Thrombolysis In Myocardial Infarction flow grade | |||
| 0 | 118 (49.6%) | 145 (57.8%) | NS |
| 1 | 20 (8.4%) | 19 (7.3%) | |
| 2 | 45 (18.9%) | 34 (13.5%) | |
| 3 | 55 (23.1%) | 53 (21.1%) | |
| Final Thrombolysis In Myocardial Infarction flow grade | 0.04 | ||
| 0 | 2 (0.8%) | 13 (5.2%) | |
| 1 | 2 (0.8%) | 3 (1.2%) | |
| 2 | 9 (3.8%) | 13 (5.2%) | |
| 3 | 225 (94.5%) | 222 (88.4%) | |
| No reflow | 7 (3%) | 3 (1.2%) | NS |
| Aspiration thrombectomy | 67 (28.3%) | 79 (31.6%) | NS |
| Drug-eluting stent | 9 (4.2%) | 16 (7.5%) | NS |
| Minimum stent diameter (mm) | 3.1 ± 0.44 | 3.1 ± 0.48 | NS |
| Total stent length (mm) | 26.7 ± 13.8 | 25.5 ± 13 | NS |
| Postdilation | 98 (43.9%) | 118 (51.5%) | NS |
| Vascular closure device | 0 | 156 (62.1%) | |
| Procedural success † | 225 (94.5%) | 222 (88.4%) | 0.02 |
| Intra-aortic balloon pump | 6 (2.5%) | 42 (16.7%) | <0.0001 |
| Coronary artery bypass graft | 7 (3%) | 10 (4%) | NS |
| Mean contrast dye volume (ml) | 215.2 ± 76.8 | 229.5 ± 94.3 | NS |
⁎ Simultaneous aspirin, clopidogrel, heparin, and glycoprotein IIb/IIIa inhibitors.
† Residual diameter stenosis of <20% with Thrombolysis in myocardial infarction flow Grade 3.
Using the radial artery led to a statistically significant lower incidence of major bleeding without increasing the time to revascularization. Major bleeding was observed in 7 patients (2.9%) in the radial group and 36 patients (14.3%) in the femoral group (p <0.0001). We did not observe any difference in bleeding rates in the femoral group between those who received a closure device and those who did not (13% vs 15%, respectively; p = 0.7). On multivariate logistic regression analysis, the use of the femoral approach was the most important independent predictor for major bleeding with an adjusted odds ratio of 5.13 (95% confidence interval 2.05 to 12.83). Weaker associations in terms of risk were found for age (odds ratio 1.06 for each year, 95% confidence interval 1.028 to 1.092) and maximum active clotting time (odds ratio 1.01, 95% confidence interval 1.001 to 1.008). In the propensity-adjusted model, the use of the femoral approach remained a strong independent predictor of bleeding, with an odds ratio of 4.22 (95% confidence interval 3.17 to 10.60). As listed Table 3 , no significant differences were observed in the time to revascularization between the 2 groups.
