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IIIa inhibition in acute myocardial infarction—the RADIAL-AMI pilot randomized trial
Radial versus femoral access for emergent percutaneous coronary intervention with adjunct glycoprotein IIb/IIIa inhibition in acute myocardial infarction—the RADIAL-AMI pilot randomized trial Warren J. Cantor, MD,a Geoff Puley, MD,a Madhu K. Natarajan, MD,b Vlad Dzavik, MD,c Mina Madan, MD,d Anne Fry, RN,a Hahn Hoe Kim, MD,a James L. Velianou, MD,b Nurry Pirani,a Bradley H. Strauss, MD, PhD,a and Robert J. Chisholm, MDa Toronto and Hamilton, Ontario, Canada
Background Transradial percutaneous coronary intervention (PCI) results in fewer vascular complications, earlier ambulation, and improved patient comfort. Limited data exist for radial access in acute myocardial infarction, where reperfusion must occur quickly. Methods In a multicenter pilot trial, 50 patients with myocardial infarction requiring either primary or rescue PCI were randomized to radial or femoral access. All operators had previously performed at least 100 transradial cases. Procedure times were prospectively recorded. Results
Thrombolysis was used in 66% of the cases and glycoprotein IIb/IIIa inhibitors in 94%. Crossover from radial to femoral access was required in one case. Percutaneous coronary intervention was performed in 47 patients, with stenting in 45. One procedural failure occurred with radial access because of inability to cross the occlusion. The time from local anesthesia to first balloon inflation was 32 (25th percentile 26, 75th percentile 38) minutes for radial access and 26 (22, 33) minutes for femoral access ( P = .04). There were no significant differences in contrast use or fluoroscopy time. No patient experienced major bleeding or required transfusion. Doppler studies demonstrated 2 asymptomatic radial occlusions and 2 pseudoaneurysms (1 from each group). One patient in the femoral group died 2 days after PCI. At 30 days, there were no strokes or reinfarctions and no patient required bypass surgery or repeat PCI.
Conclusions Primary and rescue PCI can be performed with high success rates using either radial or femoral access. Although radial access was associated with a longer time to first balloon inflation, the difference was small and likely not clinically significant. In patients without shock, major bleeding and vascular complications are infrequent with either access site despite the high use of thrombolysis and glycoprotein IIb/IIIa inhibitors. (Am Heart J 2005;150:543- 9.)
Transradial access has been used for cardiac catheterization and percutaneous coronary intervention (PCI) for N10 years.1 The reported advantages of transradial access over the more conventional transfemoral route include decreased incidence of access site bleeding and other vascular complications, earlier ambulation, and improved patient comfort.2 - 4 These benefits may be From the aSt Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada, b Hamilton Health Sciences-McMaster University, Hamilton, Ontario, Canada, cUniversity Health Network, University of Toronto, Toronto, Ontario, Canada, and dSunnybrook and Women’s Health Science, University of Toronto, Toronto, Ontario, Canada. Submitted June 29, 2004; accepted October 18, 2004. Reprint requests: Warren J. Cantor, MD, Division of Cardiology, St Michael’s Hospital, 30 Bond St, Toronto, Ontario, Canada M5B-1W8. E-mail: [email protected] 0002-8703/$ - see front matter n 2005, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2004.10.043
especially advantageous in the setting of emergent PCI for ST-elevation myocardial infarction (STEMI), where access site bleeding related to the use of thrombolysis, glycoprotein (GP) IIb/IIIa inhibitors, and other potent antithrombotic agents occurs in up to 23% of patients.5 However, published studies of transradial PCI for STEMI have been mostly retrospective and mainly limited to primary PCI.6 -13 No prospective studies have evaluated radial access for rescue PCI within 12 hours of failed thrombolytic therapy. Concerns that transradial access may delay reperfusion in primary and rescue PCI because it is more technically challenging and associated with a steep learning curve and higher access site failure rate exist.2,14 We therefore carried out a prospective, randomized multicenter pilot study to compare transradial access and transfemoral access in the setting of primary and rescue PCI.
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Methods Study population All patients with STEMI who were referred for primary or rescue PCI at participating PCI centers were screened for eligibility. For primary and rescue PCI, patients could be enrolled within 12 hours of symptom onset and within 12 hours of thrombolysis, respectively. Rescue PCI was performed for suspected failed reperfusion or reocclusion based on symptoms and electrocardiographic changes. Patients were excluded if they were in cardiogenic shock, had an abnormal Allen’s test result, or had contraindications to GP IIb/IIIa inhibitor use (active bleeding, major surgery/biopsy/significant trauma in the past 6 weeks, systolic blood pressure N200 mm Hg or diastolic blood pressure N110 mm Hg, International Normalized Ratio N2, recent noncompressible vascular puncture, central nervous system structural damage or stroke/ transient ischemic attack within the last 6 months, baseline platelet count b100 000 cells/AL). Allen’s test is performed by simultaneously occluding the radial and ulnar arteries while a patient makes a fist. The patient then opens his or her hand and the ulnar artery is released. A delay of N15 seconds before the return of color to the blanched hand was considered an abnormal Allen’s test result.15 Informed consent was obtained before the procedure in all cases. The study protocol was approved by the institutional ethics committees of each of the participating sites.
End points The primary efficacy end point of the trials was reperfusion time (time from local anesthesia infiltration to the first balloon inflation). The primary safety end points of the trial were major bleeding (intracranial or retroperitoneal bleeding, a drop in hemoglobin level N5 g/dL or hematocrit z15%, or whole blood or packed red cell transfusions) and access site complications (hematoma N5 cm, pseudoaneurysm, arteriovenous fistula, access site rebleeding after initial hemostasis) during the initial hospitalization. Routine ultrasound and Doppler studies of the access site artery were performed before hospital discharge. Other clinical end points including death, reinfarction, urgent revascularization, stroke, and new congestive heart failure were evaluated during the initial hospitalization and at 30 days. The diagnosis of reinfarction required new pathological Q waves or reelevation of creatine kinase MB higher than the upper limit of normal (ULN) (or N50% above previous level if already above normal) to z3 ULN after PCI or to z5 ULN after bypass surgery. Quality of life was assessed at 24 hours and 1 week after PCI. Self-administered questionnaires were used with the Medical Outcomes Study short form 36-item health status questionnaire (SF-36 acute)16,17 and a procedurespecific visual analog scale rating pain, discomfort, and difficulty walking on a scale from 0 to 10.4
Interventions All participating interventional cardiologists were required to have performed a minimum of 100 transradial PCI procedures before the study. Informed consent was obtained before the procedure, after confirming eligibility. Randomization was performed in a concealed manner using sealed envelopes. Crossover from one arterial access site to another was permitted at any time after randomization at the physician’s discretion.
Table I. Baseline clinical characteristics Radial (n = 25) Age (y) Women Weight (kg) Diabetes Hypertension Current smoker Hyperlipidemia Baseline heart rate Systolic blood pressure Anterior ST elevation Inferior ST elevation Primary PCI Rescue PCI
52 6 84 8 12 14 10 69 112 12 13 9 16
(48, 60) (24%) (73, 95) (32%) (48%) (56%) (42%) (65, 79) (97, 127) (50%) (52%) (36%) (64%)
Femoral (n = 25) 58 0 86 4 10 12 11 76 111 13 12 8 17
(49, 72) (0%)T (75, 90) (16%) (40%) (48%) (44%) (69, 87) (101, 122) (52%) (50%) (32%) (68%)
Values expressed as median (25th, 75th percentile) or n (%) of patients. TP b .05.
The choice of sheaths and catheters was left to the physician’s discretion. All patients received heparin (target activated clotting time, 200-300 seconds), acetylsalicylic acid (325 mg before the procedure), and clopidogrel (300 mg loading dose, 75 mg daily for a minimum of 28 days after the procedure). By protocol, all patients were to receive abciximab (a bolus of 0.25 mg/kg before or during procedure followed by an infusion of 0.125 Ag/(kgd min) [maximum of 10 Ag/min]) for 12 hours after PCI. Stenting was recommended for all PCI procedures. Medtronic balloon catheters and stents were recommended. The use of approved distal protection devices, thrombectomy devices, and vascular closure devices was permitted and left to the operators’ discretion. Cardiac markers (creatine kinase MB and troponin) were analyzed every 6 hours for the first 24 hours after PCI. Use of postprocedural heparin was discouraged.
Statistical analysis This study was designed as an exploratory pilot study to determine feasibility and estimate the event rates and required sample size for a larger definitive trial. Based on major bleeding rates reported in previous studies, it was felt that an initial evaluation of 50 patients would provide both a reasonable estimate of the incidence of major bleeding with radial and femoral approaches and preliminary data to be used to plan future studies. Baseline, procedural, and angiographic characteristics were summarized as medians with 25th and 75th percentiles for continuous measures and as percentages for discrete measures. For comparisons between groups, the likelihood ratio m2 test was used for discrete variables and the Wilcoxon rank sum was used for continuous variables.
Results Baseline characteristics Thirty-three patients undergoing rescue PCI and 17 patients undergoing primary PCI were randomized to either radial (n = 25) or femoral (n = 25) arterial access. The baseline characteristics are summarized in Table I. There were more women in the radial group (24% vs 0%, P = .009). There were no other significant differences in
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Table II. Angiographic and procedural characteristics
Crossover to other access site Sheath size (6 French/7 French) IRA Left anterior descending Left circumflex Right coronary artery Initial TIMI Flow (0-1/2/3) PCI performed Guide catheter Judkins Amplatz Voda/Extra back-up Stent used Abciximab Other GP IIb/IIIa inhibitors Distal protection device Final TIMI flow (0-1/2/3) Contrast use (mL) Fluoroscopy time (min) Vascular closure device
Radial (n = 25)
Femoral (n = 25)
1 (4%) 100%/0%
0 (0%) 88%/12%
48% 8% 44% 52%/16%/32% 23 (92%)
52% 4% 44% 48%/20%/32% 24 (96%)
3 (13%) 9 (38%) 9 (39%) 6 (25%) 11 (47%) 9 (38%) 22 (88%) 23 (92%) 20 (80%) 20 (80%) 4 (15%) 3 (12%) 1 (4%) 3 (12%) 4%/9%/87% 0%/12%/88% 210 (160, 235) 180 (150, 275) 11.3 (7.6, 15) 9 (7.2, 16.5) 0 (0%) 2 (8%)
Values expressed as median (25th, 75th percentile) or n (%) of patients. TP b .05.
patient demographics, risk factors, indication for PCI, or infarct location.
Procedural outcomes Only one patient in the radial group required crossover to femoral access because of inability to cannulate the radial artery. There were no crossovers in the femoral group. The angiographic and procedural data are shown in Table II. The infarct-related artery (IRA) was occluded (TIMI 0-1 flow) in approximately 50% of the cases in both groups. Two patients in the radial group and one patient in the femoral group did not undergo PCI. These patients had lesions b50% and TIMI-3 flow in the IRA. Another patient underwent transradial catheterization but attempts to cross the occluded IRA with a guidewire were unsuccessful. There was a trend to higher use of Judkins guide catheters with femoral access (38% vs 13%, P = .055). Stents were used in all but 2 of the PCI cases (1 in each study group). There were no differences in the number of stents used, with an average of 1.3 stents per case. Abciximab was used during the procedure in 80% of the cases and was started before arrival in the catheterization laboratory in 12%. In 15 cases (30%), eptifibatide or tirofiban was started before arrival in the catheterization laboratory. The small-molecule GP IIb/IIIa inhibitors were switched to abciximab in 8 of these cases. Only 3 patients did not receive any GP IIb/IIIa inhibitor. TIMI-3 flow was achieved in 87% of the patients in each group. There were no significant differences in total contrast use or
Table III. Procedural time intervals Radial (n = 25) Lidocaine to sheath 2 (2, 4) insertion (min) Sheath insertion to 6 (3, 8) first contrast injection (min) First contrast injection 14 (11, 22) to coronary wiring (min) Coronary wiring to 4 (2, 7) first balloon inflation (min) First balloon 6 (5, 8) inflation to stent deployment (min) Stent deployment 10 (6, 20) to guide catheter removal (min) Guide catheter 0.03 (0.01, 0.07) removal to sheath removal (h) Lidocaine to first 9 (7, 12) contrast injection (min) Lidocaine to 17 (12, 22) contrast injection of IRA (min) Lidocaine to first 32 (26, 38) balloon inflation (min) Lidocaine to guide 49 (40, 61) catheter removal (min) Symptom onset to first 6.4 (4.8, 7.7) balloon inflation (h) Thrombolysis to GP 4.7 (1.9, 9.2) IIb/IIIa inhibitor (h)T
Femoral (n = 25)
P
2 (1, 2)
.01
3 (2, 5)
.05
15 (13, 20)
.5
4 (3, 5)
.8
8 (7, 13)
.006
12 (9, 19)
.8
6.1 (4.7, 7.5)
b.0001
5 (4, 7)
.001
9 (7, 11)
.0008
26 (22, 33)
.04
47 (39, 64)
.9
7.4 (5.9, 10.7)
.2
4.1 (3.2, 5.5)
.8
Values expressed as median (25th, 75th percentile). TRescue PCI cases only (n = 33).
fluoroscopy time. Vascular closure devices were used in 2 of the patients in the femoral group. In the remaining 23 patients, manual compression was applied for 10 to 20 minutes, followed by placement of a clamp in 2 patients. There was no significant difference in the change in serum creatinine levels between the 2 groups. The initial hospital length of stay was 4 (25th percentile 3, 75th percentile 6) days in both groups.
Procedural time intervals The time intervals from initial local anesthesia infiltration of the access site to contrast injection, completion of coronary wiring, and first balloon inflation are shown in Table III. The times to sheath insertion, first contrast injection, and first balloon inflation were slightly longer with radial access. The time from balloon inflation to stent deployment was slightly longer with femoral access. Among the patients who underwent PCI,
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Figure 1
Table IV. Quality-of-life measures at 24 hours after procedure Radial (n = 23)
Number of Patients
30 25
24 21
20
p = 0.12 15 10 5 1
2
0 < 30
2 0
30 - 40
> 40
Drop in Hemoglobin (g/L) Radial
Femoral
Drops in hemoglobin levels.
the median time from lidocaine infiltration to first balloon inflation was 32 minutes for radial access and 26 minutes for femoral access ( P = .04). Most of the delay occurred between lidocaine infiltration and the first contrast injection of the IRA (17 minutes for radial, 9 minutes for femoral, P = .0008).
Clinical outcomes at 30 days Thirty-day follow-up was complete in all except in one patient in the radial group. Only one death occurred—in a patient randomized to femoral access who suffered a cardiac arrest 3 days after successful stenting. No patient experienced reinfarction or stroke and no patient required repeat PCI, bypass surgery, or vascular surgery. No patient from either group experienced major bleeding or required blood transfusion. There were nonsignificant trends to more drops in hemoglobin levels ( P = .12) (Figure 1) and more investigator-reported hematomas (28% vs 8%, P = .07) in the femoral group. Vascular ultrasound and Doppler studies Vascular ultrasound and Doppler study of the access site were performed within 1 week of the procedure in 23 patients (92%) in the radial group and 20 patients (80%) in the femoral group. In the radial group, 2 patients (9%) had asymptomatic radial occlusion detected by Doppler with no clinical sequelae. One patient from each group had pseudoaneurysms at the access site. The femoral artery pseudoaneurysm was treated successfully with local thrombin injection, and the radial pseudoaneurysm was treated conservatively and resolved completely on a follow-up Doppler study. Ultrasound evidence of access-site hematoma was present in 9% of the radial group and 20% of the femoral
SF-36 acute questionnaireT Physical functioning 73 (35, 95) Role physical 25 (0, 100) Pain index 72 (32, 84) General health perception 69 (60, 82) Vitality 50 (13, 88) Social functioning 50 (13, 88) Role emotional 67 (0, 100) Mental health index 80 (44, 92) Standardized 42 (30, 48) physical component Standardized 49 (46, 55) mental component Procedure-specific visual analog scaley Overall discomfort 2 (1, 3) Discomfort at catheter site 2 (1, 3) Back pain 0 (0, 0) Difficulty walking 0 (0, 0)
Femoral (n = 24)
65 0 48 70 40 50 67 76 33
(50, 90) (0, 25) (21, 72) (45, 82) (15, 70) (13, 100) (0, 100) (60, 92) (30, 44)
P
1.0 .07 .2 .9 .6 .9 .9 .8 .3
46 (36, 49)
3 2 1 0.5
(1, (1, (0, (0,
3) 3) 3) 2.5)
.4
.7 1.0 .1 .1
Values expressed as median (25th, 75th percentile). THigher values indicate better quality of life. yRated on a scale from 0 to 10; lower values indicate better quality of life.
Table V. Quality-of-life measures at 1 week after procedure Radial (n = 19) SF-36 acute questionnaireT Physical functioning Role physical Pain index General health perception Vitality Social functioning Role emotional Mental health index Standardized physical component Standardized mental component Procedure-specific visual analog Overall discomfort Discomfort at catheter site Back pain Difficulty walking
45 0 74 77 50 38 33 68 38
(30, 83) (0, 25) (52, 100) (52, 82) (25, 75) (25, 75) (0, 100) (52, 88) (30, 47)
42 (34, 51) scaley 1 (0, 1.5 (0, 0 (0, 0 (0,
3) 3) 1) 3)
Femoral (n = 17)
P
65 (20, 85) 25 (0, 50) 74 (72, 88) 77 (50, 95) 45 (35, 70) 45 (35, 70) 50 (17, 100) 80 (60, 84) 41 (32, 50)
.7 .3 .9 .4 .9 .2 .4 .4 .5
47 (37, 56)
.9
2 2 0 1
(1, (0, (0, (0,
3.5) 3) 2) 2)
.5 .9 .5 .3
Values expressed as median (25th, 75th percentile). THigher values indicate better quality of life. yRated on a scale from 0 to 10; lower values indicate better quality of life.
group ( P = .4). No patient in either group had arteriovenous fistulas, venous thrombosis, or plaque occupying N50% of the lumen.
Quality of life The results of the SF-36 acute survey and the procedure-specific visual analog scale for 24 hours and
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1 week after the procedure are shown in Tables IV and V. The SF-36 survey showed a trend to higher brolephysicalQ scores in the radial group at 24 hours (median score 25 vs 0, P = .07), but there were no significant differences in the other scores at 24 hours or at 1 week. On the visual analog scale, there were trends to higher median scores for back pain (1 vs 0, P = .1) and difficulty walking (0.5 vs 0, P = .1) at 24 hours and similar scores in all categories at 1 week.
Discussion In this randomized pilot study, we have shown that primary and rescue PCI can be performed with high procedural success rates using either radial or femoral access. Radial access was associated with a small but statistically significant increase in the time to first balloon inflation. In this study, no major bleeding occurred with either access route despite the frequent use of thrombolysis and GP IIb/IIIa inhibitors in most cases. Nonsignificant trends of fewer hematomas and drops in hemoglobin levels were observed with radial access. Clinical outcomes, vascular complications, and healthrelated quality of life were similar between study groups. A number of small retrospective studies have compared radial access and femoral access in patients undergoing primary PCI9-11,13,18 or rescue PCI.11-13 Four studies showed no difference in cannulation time (from patient arrival at the catheterization laboratory to the time of successful arterial sheath placement) and total procedural time.10,11,13,18 The access site complication rates were significantly lower with radial access.11,13,18 In a retrospective series of primary and rescue PCI performed at 2 centers, major bleeding (defined as hemoglobin level decline N3 g/dL) using radial access was significantly lower at one center (0% vs 7%, P b .05) and similar to that using femoral access at the other center (0% vs 2%, P = NS).13 Retrospective, nonrandomized comparisons of radial access and femoral access are, however, prone to several sources of bias. There may be important differences in baseline characteristics of patients who are selected for radial or femoral access including age, sex, and body size. Procedural factors other than access route, including sheath size, femoral vein cannulation, and intraaortic balloon pump use, may differ. Furthermore, the procedural techniques, experience, and skill levels of operators who preferentially use radial access may differ from those primarily using femoral access. The only published prospective, randomized study comparing radial access and femoral access for ST-elevation MI is the TEMPURA trial, in which no GP IIb/IIIa inhibitor was used and no patient received thrombolysis.19 There was a trend to lesssevere bleeding with radial access (0% vs 3%, P = .14), and the total procedural time was significantly shorter with radial access (44 vs 51 minutes, P = .03).
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In the present study, no patient from either study group suffered from major bleeding complications despite the use of fibrinolytic agents before PCI in 66% of the patients and GP IIb/IIIa inhibitors in 94%. In a previous study of patients undergoing transfemoral PCI with GP IIb/IIIa inhibitors within 24 hours of full-dose thrombolysis, the incidence of major bleeding (using the same criteria as in the present study) was 13% in the patients who did not receive intraaortic balloon pump placement.5 In a separate series of 111 rescue PCI cases, using the same definition for major bleeding, there was a trend to fewer major bleedings with radial access (6% vs 19%, P = .06), but the difference was much smaller after excluding patients with intraaortic balloon pumps (4% vs 8%, P = .7).12 The absence of any major bleeding or need for transfusions in the present study may be partly attributed to the small sample size and exclusion of patients in cardiogenic shock. However, this may also reflect the use of smaller sheath sizes, earlier sheath removal, lower procedural heparin doses, and avoidance of postprocedural heparin infusions in contemporary practice.20 This trial was designed as a pilot study and cannot rule out a significant difference in major bleeding rates between radial access and femoral access. However, our findings suggest that severe bleeding is uncommon with either access route and that any possible benefit of transradial PCI in reducing severe bleeding is likely to be modest. Vascular complications occurred infrequently in both treatment groups. There was a trend to fewer investigator-reported hematomas with radial access (8% vs 28%, P = .07), consistent with previous trials.3,11,18,21 Unlike previous studies, ultrasound and Doppler studies of the access site artery were performed routinely after PCI in most patients. Two patients (9%) were found to have asymptomatic radial occlusion. This finding is consistent with previous studies that have documented asymptomatic radial occlusion rates of 5% after transradial PCI.2,22 At 1 month, approximately half of these patients had spontaneous recanalization.22 Although this can be considered a minor complication, it reinforces the importance of confirming a normal Allen’s test result before radial artery cannulation. Vascular closure devices were used in only 2 patients in the femoral group. A recent meta-analysis suggests that these devices may significantly increase the risk of vascular complications.23 In this study, we observed a small but statistically significant difference in the time to first balloon inflation, with an additional 6 minutes, on average, required for transradial procedures. The delay included a slightly longer time to insert the arterial sheath and longer times required to perform angiography and engage the IRA with the guide catheter. Although previous studies have not reported longer procedural times with radial access,10,11,13,18,19 only 2 retrospective studies measured the time to first balloon inflation.11,13
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In one of these studies, 11 of 100 patients had a failed radial attempt and were not included in the timing comparisons.11 Longer sheath insertion times and more access site failures with radial access have been reported in previous randomized trials.2,21 Anatomical variations of the radial, brachial, and subclavian arteries may lead to further delays in performing angiography and PCI.24,25 Transradial PCI is associated with a steep learning curve, and procedure times are related to operator experience with transradial catheterization and PCI.14 All operators in this study had performed N100 transradial PCI procedures before the study. Therefore, the time delay related to radial access may be longer with less-experienced operators. For primary PCI, accumulating evidence demonstrate that mortality is increased with delays in reperfusion.26 -29 Under most circumstances, it is unlikely that a short delay such as that seen in this trial would be clinically significant. Nevertheless, choice of access site may be an important consideration for sites that perform primary PCI with door-to-balloon times that often exceed guideline recommendations of 90 minutes.30,31 Although the time to first balloon inflation was longer with radial access, the time from the first balloon inflation to the first stent deployment was significantly longer with femoral access (8 vs 6 minutes, P = .006). This time interval was not a primary end point and the difference may be related to chance. However, it is possible that the more aggressive guide catheter configurations (Amplatz, Voda/Extra Back-Up) that are used more frequently with radial access (90% vs 63%, P = .055) allow for quicker and easier delivery of the stent across the lesion. The longer time to first balloon inflation and shorter time to stent deployment with radial access in this study resulted in total procedural times that were very similar with radial access and femoral access, which may explain the similar total procedural times documented in previous studies.10,11,13,18 Quality of life was evaluated at 24 hours and 1 week after PCI using the same questionnaires and visual analog scales used in a previous trial of radial versus femoral diagnostic cardiac catheterization.4 Cooper et al4 demonstrated statistically significant improvements across multiple indices of quality of life with transradial diagnostic catheterization, both at 24 hours and 1 week. In this study, there were only nonsignificant trends to improved quality of life with radial access at 24 hours. The difference between these results and those seen in the previous study may be related to the smaller sample size. Any subjective difference in access site and back pain between radial access and femoral access is likely overshadowed by the severe, prolonged chest pain that patients with acute MI experience before reperfusion. Furthermore, patients with acute MI are hospitalized for a minimum of 3 days and are slower to ambulate, negating some of the benefits of transradial access.
Conclusions Transradial access for primary or rescue PCI is feasible with high success rates similar to femoral access when performed by experienced operators. Although radial access was associated with a longer time to reperfusion, the difference was small and likely not clinically significant. In patients without shock, major bleeding and vascular complications are infrequent with either access site despite the high use of thrombolysis and GP IIb/IIIa inhibitors.
References 1. Kiemeneij F, Laarman GJ. Percutaneous transradial artery approach for coronary stent implantation. Catheter Cardiovasc Diagn 1993; 30:173 - 8. 2. Kiemeneij F, Laarman GJ, Odekerken D, et al. A randomized comparison of percutaneous transluminal coronary angioplasty by the radial, brachial and femoral approaches: the Access Study. J Am Coll Cardiol 1997;29:1269 - 75. 3. Mann T, Cubeddu G, Bowen J, et al. Stenting in acute coronary syndromes: a comparison of radial versus femoral access sites. J Am Coll Cardiol 1998;32:572 - 6. 4. Cooper CJ, El Shiekh RA, Cohen DJ, et al. Effect of transradial access on quality of life and cost of cardiac catheterization: a randomized comparison. Am Heart J 1999;138:430 - 6. 5. Cantor WJ, Kaplan AL, Velianou JL, et al. Effectiveness and safety of abciximab after failed thrombolytic therapy. Am J Cardiol 2001;87: 439 - 42. 6. Ochiai M, Isshiki T, Toyoizumi H, et al. Efficacy of transradial primary stenting in patients with acute myocardial infarction. Am J Cardiol 1999;83:966 - 8. 7. Steg G, Aubry P. Radial access for primary PTCA in patients with acute myocardial infarction and contraindication or impossible femoral access. Catheter Cardiovasc Diagn 1996;39:424 - 6. 8. Mulukutia SR, Cohen HA. Feasibility and efficacy of transradial access for coronary interventions in patients with acute myocardial infarction. Catheter Cardiovasc Interv 2002;57:167 - 71. 9. Mathias DW, Bigler L. Transradial coronary angioplasty and stent implantation in acute myocardial infarction: initial experience. J Invasive Cardiol 2002;12:547 - 9. 10. Kim MH, Cha KS, Kim HJ, et al. Primary stenting for acute myocardial infarction via transradial approach: a safe and useful alternative to the transfemoral approach. J Invasive Cardiol 2000; 12:292 - 6. 11. Ziakas A, Klinke P, Mildenberger R, et al. Comparison of the radial and the femoral approaches in percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2003;91:598 - 600. 12. Kassam S, Cantor WJ, Patel D, et al. Radial vs femoral access for rescue percutaneous coronary intervention with adjuvant glycoprotein IIb/IIIa inhibitor use. Can J Cardiol 2004 [in press]. 13. Louvard Y, Ludwig J, Lefevre T, et al. Transradial approach for coronary angioplasty in the setting of acute myocardial infarction: a dual-center registry. Catheter Cardiovasc Interv 2002;55:206 - 11. 14. Goldberg SL, Renslo R, Sinow R, et al. Learning curve in the use of the radial artery as vascular access in the performance of percutaneous transluminal coronary angioplasty. Catheter Cardiovasc Diagn 1998;44:147 - 52. 15. Mick MJ. Transradial approach for coronary angiography. J Invasive Cardiol 1996;8(Suppl D):9D - 12D.
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16. Tarlov AR, Ware Jr JE, Greenfield S, et al. The Medical Outcomes Study. An application of methods for monitoring the results of medical care. JAMA 1989;262:925 - 30. 17. Stewart AL, Hays RD, Ware Jr JE. The MOS short-form general health survey: reliability and validity in a patient population. Med Care 1989;27:S217 - 31. 18. Philippe F, Larrazet F, Meziane T, et al. Comparison of transradial vs transfemoral approach in the treatment of acute myocardial infarction with primary angioplasty and abciximab. Catheter Cardiovasc Interv 2004;61:67 - 73. 19. Saito S, Tanaka S, Hiroe Y, et al. Comparative study on transradial approach vs transfemoral approach in primary stent implantation for patients with acute myocardial infarction: results of the Test for Myocardial Infarction by Prospective Unicenter Randomization for Access Sites (TEMPURA) trial. Catheter Cardiovasc Interv 2003; 59:26 - 33. 20. Lincoff AM, Tcheng JE, Califf RM, et al. Standard versus low-dose weight–adjusted heparin in patients treated with the platelet glycoprotein IIb/IIIa receptor antibody fragment abciximab (c7E3 Fab) during percutaneous coronary revascularization. Am J Cardiol 1997;79:286 - 91. 21. Reddy BK, Brewster PS, Walsh T, et al. Randomized comparison of rapid ambulation using radial, 4 French femoral access, or femoral access with AngioSeal closure. Catheter Cardiovasc Interv 2004; 62:143 - 9. 22. Stella PR, Kiemeneij F, Laarman GJ, et al. Incidence and outcome of radial artery occlusion following transradial artery coronary angioplasty. Catheter Cardiovasc Diagn 1997;40:156 - 8. 23. Koreny M, Riedmuller E, Nikfardjam M, et al. Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: systematic review and meta-analysis. JAMA 2004;291:350 - 7.
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24. Yokoyama N, Takeshita S, Ochiai M, et al. Anatomic variations of the radial artery in patients undergoing transradial coronary intervention. Catheter Cardiovasc Interv 2000;49:357 - 62. 25. Abhaichand RK, Louvard Y, Gobeil JF, et al. The problem of arteria lusoria in right transradial coronary angiography and angioplasty. Catheter Cardiovasc Interv 2001;54:196 - 201. 26. Cannon CP, Gibson CM, Lambrew CT, et al. Relationship of symptom-onset–to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA 2000;283:2941 - 7. 27. Nallamothu BK, Bates ER. Percutaneous coronary intervention versus fibrinolytic therapy in acute myocardial infarction: is timing (almost) everything? Am J Cardiol 2003;92:824 - 6. 28. Brodie BR, Kissling G, Berger PB, et al. Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction response. Circulation 2000;102:e29 - e30. 29. De Luca G, Suryapranata H, Ottervanger JP, et al. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation 2004;109: 1223 - 5. 30. Ryan TJ, Antman EM, Brooks NH, et al. 1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol 1999;34:890 - 911. 31. Van de WF, Ardissino D, Betriu A, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J 2003; 24:28 - 66.
Background Transradial percutaneous coronary intervention (PCI) results in fewer vascular complications, earlier ambulation, and improved patient comfort. Limited data exist for radial access in acute myocardial infarction, where reperfusion must occur quickly. Methods In a multicenter pilot trial, 50 patients with myocardial infarction requiring either primary or rescue PCI were randomized to radial or femoral access. All operators had previously performed at least 100 transradial cases. Procedure times were prospectively recorded. Results
Thrombolysis was used in 66% of the cases and glycoprotein IIb/IIIa inhibitors in 94%. Crossover from radial to femoral access was required in one case. Percutaneous coronary intervention was performed in 47 patients, with stenting in 45. One procedural failure occurred with radial access because of inability to cross the occlusion. The time from local anesthesia to first balloon inflation was 32 (25th percentile 26, 75th percentile 38) minutes for radial access and 26 (22, 33) minutes for femoral access ( P = .04). There were no significant differences in contrast use or fluoroscopy time. No patient experienced major bleeding or required transfusion. Doppler studies demonstrated 2 asymptomatic radial occlusions and 2 pseudoaneurysms (1 from each group). One patient in the femoral group died 2 days after PCI. At 30 days, there were no strokes or reinfarctions and no patient required bypass surgery or repeat PCI.
Conclusions Primary and rescue PCI can be performed with high success rates using either radial or femoral access. Although radial access was associated with a longer time to first balloon inflation, the difference was small and likely not clinically significant. In patients without shock, major bleeding and vascular complications are infrequent with either access site despite the high use of thrombolysis and glycoprotein IIb/IIIa inhibitors. (Am Heart J 2005;150:543- 9.)
Transradial access has been used for cardiac catheterization and percutaneous coronary intervention (PCI) for N10 years.1 The reported advantages of transradial access over the more conventional transfemoral route include decreased incidence of access site bleeding and other vascular complications, earlier ambulation, and improved patient comfort.2 - 4 These benefits may be From the aSt Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada, b Hamilton Health Sciences-McMaster University, Hamilton, Ontario, Canada, cUniversity Health Network, University of Toronto, Toronto, Ontario, Canada, and dSunnybrook and Women’s Health Science, University of Toronto, Toronto, Ontario, Canada. Submitted June 29, 2004; accepted October 18, 2004. Reprint requests: Warren J. Cantor, MD, Division of Cardiology, St Michael’s Hospital, 30 Bond St, Toronto, Ontario, Canada M5B-1W8. E-mail: [email protected] 0002-8703/$ - see front matter n 2005, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2004.10.043
especially advantageous in the setting of emergent PCI for ST-elevation myocardial infarction (STEMI), where access site bleeding related to the use of thrombolysis, glycoprotein (GP) IIb/IIIa inhibitors, and other potent antithrombotic agents occurs in up to 23% of patients.5 However, published studies of transradial PCI for STEMI have been mostly retrospective and mainly limited to primary PCI.6 -13 No prospective studies have evaluated radial access for rescue PCI within 12 hours of failed thrombolytic therapy. Concerns that transradial access may delay reperfusion in primary and rescue PCI because it is more technically challenging and associated with a steep learning curve and higher access site failure rate exist.2,14 We therefore carried out a prospective, randomized multicenter pilot study to compare transradial access and transfemoral access in the setting of primary and rescue PCI.
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Methods Study population All patients with STEMI who were referred for primary or rescue PCI at participating PCI centers were screened for eligibility. For primary and rescue PCI, patients could be enrolled within 12 hours of symptom onset and within 12 hours of thrombolysis, respectively. Rescue PCI was performed for suspected failed reperfusion or reocclusion based on symptoms and electrocardiographic changes. Patients were excluded if they were in cardiogenic shock, had an abnormal Allen’s test result, or had contraindications to GP IIb/IIIa inhibitor use (active bleeding, major surgery/biopsy/significant trauma in the past 6 weeks, systolic blood pressure N200 mm Hg or diastolic blood pressure N110 mm Hg, International Normalized Ratio N2, recent noncompressible vascular puncture, central nervous system structural damage or stroke/ transient ischemic attack within the last 6 months, baseline platelet count b100 000 cells/AL). Allen’s test is performed by simultaneously occluding the radial and ulnar arteries while a patient makes a fist. The patient then opens his or her hand and the ulnar artery is released. A delay of N15 seconds before the return of color to the blanched hand was considered an abnormal Allen’s test result.15 Informed consent was obtained before the procedure in all cases. The study protocol was approved by the institutional ethics committees of each of the participating sites.
End points The primary efficacy end point of the trials was reperfusion time (time from local anesthesia infiltration to the first balloon inflation). The primary safety end points of the trial were major bleeding (intracranial or retroperitoneal bleeding, a drop in hemoglobin level N5 g/dL or hematocrit z15%, or whole blood or packed red cell transfusions) and access site complications (hematoma N5 cm, pseudoaneurysm, arteriovenous fistula, access site rebleeding after initial hemostasis) during the initial hospitalization. Routine ultrasound and Doppler studies of the access site artery were performed before hospital discharge. Other clinical end points including death, reinfarction, urgent revascularization, stroke, and new congestive heart failure were evaluated during the initial hospitalization and at 30 days. The diagnosis of reinfarction required new pathological Q waves or reelevation of creatine kinase MB higher than the upper limit of normal (ULN) (or N50% above previous level if already above normal) to z3 ULN after PCI or to z5 ULN after bypass surgery. Quality of life was assessed at 24 hours and 1 week after PCI. Self-administered questionnaires were used with the Medical Outcomes Study short form 36-item health status questionnaire (SF-36 acute)16,17 and a procedurespecific visual analog scale rating pain, discomfort, and difficulty walking on a scale from 0 to 10.4
Interventions All participating interventional cardiologists were required to have performed a minimum of 100 transradial PCI procedures before the study. Informed consent was obtained before the procedure, after confirming eligibility. Randomization was performed in a concealed manner using sealed envelopes. Crossover from one arterial access site to another was permitted at any time after randomization at the physician’s discretion.
Table I. Baseline clinical characteristics Radial (n = 25) Age (y) Women Weight (kg) Diabetes Hypertension Current smoker Hyperlipidemia Baseline heart rate Systolic blood pressure Anterior ST elevation Inferior ST elevation Primary PCI Rescue PCI
52 6 84 8 12 14 10 69 112 12 13 9 16
(48, 60) (24%) (73, 95) (32%) (48%) (56%) (42%) (65, 79) (97, 127) (50%) (52%) (36%) (64%)
Femoral (n = 25) 58 0 86 4 10 12 11 76 111 13 12 8 17
(49, 72) (0%)T (75, 90) (16%) (40%) (48%) (44%) (69, 87) (101, 122) (52%) (50%) (32%) (68%)
Values expressed as median (25th, 75th percentile) or n (%) of patients. TP b .05.
The choice of sheaths and catheters was left to the physician’s discretion. All patients received heparin (target activated clotting time, 200-300 seconds), acetylsalicylic acid (325 mg before the procedure), and clopidogrel (300 mg loading dose, 75 mg daily for a minimum of 28 days after the procedure). By protocol, all patients were to receive abciximab (a bolus of 0.25 mg/kg before or during procedure followed by an infusion of 0.125 Ag/(kgd min) [maximum of 10 Ag/min]) for 12 hours after PCI. Stenting was recommended for all PCI procedures. Medtronic balloon catheters and stents were recommended. The use of approved distal protection devices, thrombectomy devices, and vascular closure devices was permitted and left to the operators’ discretion. Cardiac markers (creatine kinase MB and troponin) were analyzed every 6 hours for the first 24 hours after PCI. Use of postprocedural heparin was discouraged.
Statistical analysis This study was designed as an exploratory pilot study to determine feasibility and estimate the event rates and required sample size for a larger definitive trial. Based on major bleeding rates reported in previous studies, it was felt that an initial evaluation of 50 patients would provide both a reasonable estimate of the incidence of major bleeding with radial and femoral approaches and preliminary data to be used to plan future studies. Baseline, procedural, and angiographic characteristics were summarized as medians with 25th and 75th percentiles for continuous measures and as percentages for discrete measures. For comparisons between groups, the likelihood ratio m2 test was used for discrete variables and the Wilcoxon rank sum was used for continuous variables.
Results Baseline characteristics Thirty-three patients undergoing rescue PCI and 17 patients undergoing primary PCI were randomized to either radial (n = 25) or femoral (n = 25) arterial access. The baseline characteristics are summarized in Table I. There were more women in the radial group (24% vs 0%, P = .009). There were no other significant differences in
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Table II. Angiographic and procedural characteristics
Crossover to other access site Sheath size (6 French/7 French) IRA Left anterior descending Left circumflex Right coronary artery Initial TIMI Flow (0-1/2/3) PCI performed Guide catheter Judkins Amplatz Voda/Extra back-up Stent used Abciximab Other GP IIb/IIIa inhibitors Distal protection device Final TIMI flow (0-1/2/3) Contrast use (mL) Fluoroscopy time (min) Vascular closure device
Radial (n = 25)
Femoral (n = 25)
1 (4%) 100%/0%
0 (0%) 88%/12%
48% 8% 44% 52%/16%/32% 23 (92%)
52% 4% 44% 48%/20%/32% 24 (96%)
3 (13%) 9 (38%) 9 (39%) 6 (25%) 11 (47%) 9 (38%) 22 (88%) 23 (92%) 20 (80%) 20 (80%) 4 (15%) 3 (12%) 1 (4%) 3 (12%) 4%/9%/87% 0%/12%/88% 210 (160, 235) 180 (150, 275) 11.3 (7.6, 15) 9 (7.2, 16.5) 0 (0%) 2 (8%)
Values expressed as median (25th, 75th percentile) or n (%) of patients. TP b .05.
patient demographics, risk factors, indication for PCI, or infarct location.
Procedural outcomes Only one patient in the radial group required crossover to femoral access because of inability to cannulate the radial artery. There were no crossovers in the femoral group. The angiographic and procedural data are shown in Table II. The infarct-related artery (IRA) was occluded (TIMI 0-1 flow) in approximately 50% of the cases in both groups. Two patients in the radial group and one patient in the femoral group did not undergo PCI. These patients had lesions b50% and TIMI-3 flow in the IRA. Another patient underwent transradial catheterization but attempts to cross the occluded IRA with a guidewire were unsuccessful. There was a trend to higher use of Judkins guide catheters with femoral access (38% vs 13%, P = .055). Stents were used in all but 2 of the PCI cases (1 in each study group). There were no differences in the number of stents used, with an average of 1.3 stents per case. Abciximab was used during the procedure in 80% of the cases and was started before arrival in the catheterization laboratory in 12%. In 15 cases (30%), eptifibatide or tirofiban was started before arrival in the catheterization laboratory. The small-molecule GP IIb/IIIa inhibitors were switched to abciximab in 8 of these cases. Only 3 patients did not receive any GP IIb/IIIa inhibitor. TIMI-3 flow was achieved in 87% of the patients in each group. There were no significant differences in total contrast use or
Table III. Procedural time intervals Radial (n = 25) Lidocaine to sheath 2 (2, 4) insertion (min) Sheath insertion to 6 (3, 8) first contrast injection (min) First contrast injection 14 (11, 22) to coronary wiring (min) Coronary wiring to 4 (2, 7) first balloon inflation (min) First balloon 6 (5, 8) inflation to stent deployment (min) Stent deployment 10 (6, 20) to guide catheter removal (min) Guide catheter 0.03 (0.01, 0.07) removal to sheath removal (h) Lidocaine to first 9 (7, 12) contrast injection (min) Lidocaine to 17 (12, 22) contrast injection of IRA (min) Lidocaine to first 32 (26, 38) balloon inflation (min) Lidocaine to guide 49 (40, 61) catheter removal (min) Symptom onset to first 6.4 (4.8, 7.7) balloon inflation (h) Thrombolysis to GP 4.7 (1.9, 9.2) IIb/IIIa inhibitor (h)T
Femoral (n = 25)
P
2 (1, 2)
.01
3 (2, 5)
.05
15 (13, 20)
.5
4 (3, 5)
.8
8 (7, 13)
.006
12 (9, 19)
.8
6.1 (4.7, 7.5)
b.0001
5 (4, 7)
.001
9 (7, 11)
.0008
26 (22, 33)
.04
47 (39, 64)
.9
7.4 (5.9, 10.7)
.2
4.1 (3.2, 5.5)
.8
Values expressed as median (25th, 75th percentile). TRescue PCI cases only (n = 33).
fluoroscopy time. Vascular closure devices were used in 2 of the patients in the femoral group. In the remaining 23 patients, manual compression was applied for 10 to 20 minutes, followed by placement of a clamp in 2 patients. There was no significant difference in the change in serum creatinine levels between the 2 groups. The initial hospital length of stay was 4 (25th percentile 3, 75th percentile 6) days in both groups.
Procedural time intervals The time intervals from initial local anesthesia infiltration of the access site to contrast injection, completion of coronary wiring, and first balloon inflation are shown in Table III. The times to sheath insertion, first contrast injection, and first balloon inflation were slightly longer with radial access. The time from balloon inflation to stent deployment was slightly longer with femoral access. Among the patients who underwent PCI,
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Figure 1
Table IV. Quality-of-life measures at 24 hours after procedure Radial (n = 23)
Number of Patients
30 25
24 21
20
p = 0.12 15 10 5 1
2
0 < 30
2 0
30 - 40
> 40
Drop in Hemoglobin (g/L) Radial
Femoral
Drops in hemoglobin levels.
the median time from lidocaine infiltration to first balloon inflation was 32 minutes for radial access and 26 minutes for femoral access ( P = .04). Most of the delay occurred between lidocaine infiltration and the first contrast injection of the IRA (17 minutes for radial, 9 minutes for femoral, P = .0008).
Clinical outcomes at 30 days Thirty-day follow-up was complete in all except in one patient in the radial group. Only one death occurred—in a patient randomized to femoral access who suffered a cardiac arrest 3 days after successful stenting. No patient experienced reinfarction or stroke and no patient required repeat PCI, bypass surgery, or vascular surgery. No patient from either group experienced major bleeding or required blood transfusion. There were nonsignificant trends to more drops in hemoglobin levels ( P = .12) (Figure 1) and more investigator-reported hematomas (28% vs 8%, P = .07) in the femoral group. Vascular ultrasound and Doppler studies Vascular ultrasound and Doppler study of the access site were performed within 1 week of the procedure in 23 patients (92%) in the radial group and 20 patients (80%) in the femoral group. In the radial group, 2 patients (9%) had asymptomatic radial occlusion detected by Doppler with no clinical sequelae. One patient from each group had pseudoaneurysms at the access site. The femoral artery pseudoaneurysm was treated successfully with local thrombin injection, and the radial pseudoaneurysm was treated conservatively and resolved completely on a follow-up Doppler study. Ultrasound evidence of access-site hematoma was present in 9% of the radial group and 20% of the femoral
SF-36 acute questionnaireT Physical functioning 73 (35, 95) Role physical 25 (0, 100) Pain index 72 (32, 84) General health perception 69 (60, 82) Vitality 50 (13, 88) Social functioning 50 (13, 88) Role emotional 67 (0, 100) Mental health index 80 (44, 92) Standardized 42 (30, 48) physical component Standardized 49 (46, 55) mental component Procedure-specific visual analog scaley Overall discomfort 2 (1, 3) Discomfort at catheter site 2 (1, 3) Back pain 0 (0, 0) Difficulty walking 0 (0, 0)
Femoral (n = 24)
65 0 48 70 40 50 67 76 33
(50, 90) (0, 25) (21, 72) (45, 82) (15, 70) (13, 100) (0, 100) (60, 92) (30, 44)
P
1.0 .07 .2 .9 .6 .9 .9 .8 .3
46 (36, 49)
3 2 1 0.5
(1, (1, (0, (0,
3) 3) 3) 2.5)
.4
.7 1.0 .1 .1
Values expressed as median (25th, 75th percentile). THigher values indicate better quality of life. yRated on a scale from 0 to 10; lower values indicate better quality of life.
Table V. Quality-of-life measures at 1 week after procedure Radial (n = 19) SF-36 acute questionnaireT Physical functioning Role physical Pain index General health perception Vitality Social functioning Role emotional Mental health index Standardized physical component Standardized mental component Procedure-specific visual analog Overall discomfort Discomfort at catheter site Back pain Difficulty walking
45 0 74 77 50 38 33 68 38
(30, 83) (0, 25) (52, 100) (52, 82) (25, 75) (25, 75) (0, 100) (52, 88) (30, 47)
42 (34, 51) scaley 1 (0, 1.5 (0, 0 (0, 0 (0,
3) 3) 1) 3)
Femoral (n = 17)
P
65 (20, 85) 25 (0, 50) 74 (72, 88) 77 (50, 95) 45 (35, 70) 45 (35, 70) 50 (17, 100) 80 (60, 84) 41 (32, 50)
.7 .3 .9 .4 .9 .2 .4 .4 .5
47 (37, 56)
.9
2 2 0 1
(1, (0, (0, (0,
3.5) 3) 2) 2)
.5 .9 .5 .3
Values expressed as median (25th, 75th percentile). THigher values indicate better quality of life. yRated on a scale from 0 to 10; lower values indicate better quality of life.
group ( P = .4). No patient in either group had arteriovenous fistulas, venous thrombosis, or plaque occupying N50% of the lumen.
Quality of life The results of the SF-36 acute survey and the procedure-specific visual analog scale for 24 hours and
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1 week after the procedure are shown in Tables IV and V. The SF-36 survey showed a trend to higher brolephysicalQ scores in the radial group at 24 hours (median score 25 vs 0, P = .07), but there were no significant differences in the other scores at 24 hours or at 1 week. On the visual analog scale, there were trends to higher median scores for back pain (1 vs 0, P = .1) and difficulty walking (0.5 vs 0, P = .1) at 24 hours and similar scores in all categories at 1 week.
Discussion In this randomized pilot study, we have shown that primary and rescue PCI can be performed with high procedural success rates using either radial or femoral access. Radial access was associated with a small but statistically significant increase in the time to first balloon inflation. In this study, no major bleeding occurred with either access route despite the frequent use of thrombolysis and GP IIb/IIIa inhibitors in most cases. Nonsignificant trends of fewer hematomas and drops in hemoglobin levels were observed with radial access. Clinical outcomes, vascular complications, and healthrelated quality of life were similar between study groups. A number of small retrospective studies have compared radial access and femoral access in patients undergoing primary PCI9-11,13,18 or rescue PCI.11-13 Four studies showed no difference in cannulation time (from patient arrival at the catheterization laboratory to the time of successful arterial sheath placement) and total procedural time.10,11,13,18 The access site complication rates were significantly lower with radial access.11,13,18 In a retrospective series of primary and rescue PCI performed at 2 centers, major bleeding (defined as hemoglobin level decline N3 g/dL) using radial access was significantly lower at one center (0% vs 7%, P b .05) and similar to that using femoral access at the other center (0% vs 2%, P = NS).13 Retrospective, nonrandomized comparisons of radial access and femoral access are, however, prone to several sources of bias. There may be important differences in baseline characteristics of patients who are selected for radial or femoral access including age, sex, and body size. Procedural factors other than access route, including sheath size, femoral vein cannulation, and intraaortic balloon pump use, may differ. Furthermore, the procedural techniques, experience, and skill levels of operators who preferentially use radial access may differ from those primarily using femoral access. The only published prospective, randomized study comparing radial access and femoral access for ST-elevation MI is the TEMPURA trial, in which no GP IIb/IIIa inhibitor was used and no patient received thrombolysis.19 There was a trend to lesssevere bleeding with radial access (0% vs 3%, P = .14), and the total procedural time was significantly shorter with radial access (44 vs 51 minutes, P = .03).
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In the present study, no patient from either study group suffered from major bleeding complications despite the use of fibrinolytic agents before PCI in 66% of the patients and GP IIb/IIIa inhibitors in 94%. In a previous study of patients undergoing transfemoral PCI with GP IIb/IIIa inhibitors within 24 hours of full-dose thrombolysis, the incidence of major bleeding (using the same criteria as in the present study) was 13% in the patients who did not receive intraaortic balloon pump placement.5 In a separate series of 111 rescue PCI cases, using the same definition for major bleeding, there was a trend to fewer major bleedings with radial access (6% vs 19%, P = .06), but the difference was much smaller after excluding patients with intraaortic balloon pumps (4% vs 8%, P = .7).12 The absence of any major bleeding or need for transfusions in the present study may be partly attributed to the small sample size and exclusion of patients in cardiogenic shock. However, this may also reflect the use of smaller sheath sizes, earlier sheath removal, lower procedural heparin doses, and avoidance of postprocedural heparin infusions in contemporary practice.20 This trial was designed as a pilot study and cannot rule out a significant difference in major bleeding rates between radial access and femoral access. However, our findings suggest that severe bleeding is uncommon with either access route and that any possible benefit of transradial PCI in reducing severe bleeding is likely to be modest. Vascular complications occurred infrequently in both treatment groups. There was a trend to fewer investigator-reported hematomas with radial access (8% vs 28%, P = .07), consistent with previous trials.3,11,18,21 Unlike previous studies, ultrasound and Doppler studies of the access site artery were performed routinely after PCI in most patients. Two patients (9%) were found to have asymptomatic radial occlusion. This finding is consistent with previous studies that have documented asymptomatic radial occlusion rates of 5% after transradial PCI.2,22 At 1 month, approximately half of these patients had spontaneous recanalization.22 Although this can be considered a minor complication, it reinforces the importance of confirming a normal Allen’s test result before radial artery cannulation. Vascular closure devices were used in only 2 patients in the femoral group. A recent meta-analysis suggests that these devices may significantly increase the risk of vascular complications.23 In this study, we observed a small but statistically significant difference in the time to first balloon inflation, with an additional 6 minutes, on average, required for transradial procedures. The delay included a slightly longer time to insert the arterial sheath and longer times required to perform angiography and engage the IRA with the guide catheter. Although previous studies have not reported longer procedural times with radial access,10,11,13,18,19 only 2 retrospective studies measured the time to first balloon inflation.11,13
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In one of these studies, 11 of 100 patients had a failed radial attempt and were not included in the timing comparisons.11 Longer sheath insertion times and more access site failures with radial access have been reported in previous randomized trials.2,21 Anatomical variations of the radial, brachial, and subclavian arteries may lead to further delays in performing angiography and PCI.24,25 Transradial PCI is associated with a steep learning curve, and procedure times are related to operator experience with transradial catheterization and PCI.14 All operators in this study had performed N100 transradial PCI procedures before the study. Therefore, the time delay related to radial access may be longer with less-experienced operators. For primary PCI, accumulating evidence demonstrate that mortality is increased with delays in reperfusion.26 -29 Under most circumstances, it is unlikely that a short delay such as that seen in this trial would be clinically significant. Nevertheless, choice of access site may be an important consideration for sites that perform primary PCI with door-to-balloon times that often exceed guideline recommendations of 90 minutes.30,31 Although the time to first balloon inflation was longer with radial access, the time from the first balloon inflation to the first stent deployment was significantly longer with femoral access (8 vs 6 minutes, P = .006). This time interval was not a primary end point and the difference may be related to chance. However, it is possible that the more aggressive guide catheter configurations (Amplatz, Voda/Extra Back-Up) that are used more frequently with radial access (90% vs 63%, P = .055) allow for quicker and easier delivery of the stent across the lesion. The longer time to first balloon inflation and shorter time to stent deployment with radial access in this study resulted in total procedural times that were very similar with radial access and femoral access, which may explain the similar total procedural times documented in previous studies.10,11,13,18 Quality of life was evaluated at 24 hours and 1 week after PCI using the same questionnaires and visual analog scales used in a previous trial of radial versus femoral diagnostic cardiac catheterization.4 Cooper et al4 demonstrated statistically significant improvements across multiple indices of quality of life with transradial diagnostic catheterization, both at 24 hours and 1 week. In this study, there were only nonsignificant trends to improved quality of life with radial access at 24 hours. The difference between these results and those seen in the previous study may be related to the smaller sample size. Any subjective difference in access site and back pain between radial access and femoral access is likely overshadowed by the severe, prolonged chest pain that patients with acute MI experience before reperfusion. Furthermore, patients with acute MI are hospitalized for a minimum of 3 days and are slower to ambulate, negating some of the benefits of transradial access.
Conclusions Transradial access for primary or rescue PCI is feasible with high success rates similar to femoral access when performed by experienced operators. Although radial access was associated with a longer time to reperfusion, the difference was small and likely not clinically significant. In patients without shock, major bleeding and vascular complications are infrequent with either access site despite the high use of thrombolysis and GP IIb/IIIa inhibitors.
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