Randomized Comparison of Radial Versus Femoral Approach for Patients With STEMI Undergoing Early PCI Following Intravenous Thrombolysis

Abstract: Background. Early percutaneous coronary intervention (PCI) following thrombolysis may be beneficial in patients with ST-segment elevation myocardial infarction (STEMI) who were admitted at a non-PCI hospital. The aim of this study was to evaluate the safety and efficacy of the radial artery as a vascular route for early PCI following thrombolysis in patients with STEMI. Methods. All consecutive STEMI patients within 12 hours after thrombolysis were enrolled, and eligible patients were randomly assigned to either transfemoral (TFI group) or transradial catheterization (TRI group). Several time intervals were measured. The puncture success rate and ambulation time were assessed. The vascular access-site complications were also assessed after the PCI procedure, and the incidence of major adverse cardiac events (MACE) in hospital was observed. Results. A total of 119 cases were enrolled, with 60 in the TRI group and 59 in the TFI group. There were no significant differences in transfer time and total procedure time. The puncture time in the TRI group was not significantly different compared to the TFI group. The time between PCI and ambulation in the TRI group was shorter than in the TFI group. There was a trend toward lower in the incidence of bleeding complications and vascular complications in the TRI group. Conclusion. TRI for STEMI patients following intravenous thrombolysis was as safe and feasible as TFI, with a trend toward lower incidence of bleeding complications and vascular complications.

J INVASIVE CARDIOL 2012;24(8):412-416

Key words: ST-segment elevation myocardial infarction, percutaneous coronary intervention, radial artery approach, thrombolysis, major adverse cardiac event

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In the setting of ST-segment elevation myocardial infarction (STEMI), the rapid recovery of TIMI 3 flow of infarct-related artery (IRA) is one of the most important prognostic factors.¹ Up to now, primary percutaneous coronary intervention (PCI) has been accepted as the optimal strategy to recanalize IRA in STEMI.² However, as the efficacy of primary PCI is time-dependent, logistical barriers limit its use to no more than 20% of STEMI patients worldwide.^3-5 As a result, early PCI following thrombolysis may be beneficial in STEMI patients who were admitted at a non-PCI hospital.

Under these conditions of aggressive anti-coagulation and anti-platelet treatments, bleeding complications during PCI could result in increased mortality after PCI procedure.^6-8 There is an increasing amount of data suggesting that transradial PCI (TRI) could reduce bleeding complications and improve long-term outcomes when compared with procedures carried out via transfemoral artery approach (TFI).^9,10

However, published studies of TRI for STEMI have been mostly retrospective, non-randomized observations limited to primary or rescue PCI.^11-14 Therefore, this study was designed to evaluate the safety and efficacy of the radial artery as a vascular route for STEMI patients undergoing early PCI following thrombolysis.

Methods

Patient group. From July 2008 to December 2010, all consecutive STEMI patients who were to receive routine early PCI within 12 hours after thrombolysis were enrolled. Eligible patients were 1:1 randomly assigned to transfemoral (TFI group) or transradial catheterization (TRI group) by a computer generation (in 2 blocks in a 1:1 ratio). Inclusion criteria included: (1) typical clinical presentation; (2) ST elevation of over 0.2 mm in 2 or more adjacent precordial leads or 0.1 mm in adjacent limb leads, or new left bundle branch block; (3) received intravenous thrombolysis within 6 hours from symptom onset in the non-PCI hospital; and (4) admitted to our hospital within 12 hours after intravenous thrombolysis.

The following exclusion criteria were used: contradictions of thrombolysis; history of coronary artery bypass surgery (CABG); cardiogenic shock; known difficulties with the femoral (ie, Leriche syndrome, severe peripheral artery disease, large abdominal aortic aneurysm) or radial approach (ie, Raynaud syndrome); a pathologic Allen’s test; necessity for a preprocedural implantation of a transient pacemaker or IABP; chronic renal insufficiency (creatinine ≥2.0 mg/dL) with the potential necessity of using the radial artery as a native fistula in the future; hemodialysis patients with an arteriovenous fistula; or patient refusal.

The study protocol was approved by the Ethical Committee of the Second Hospital of Hebei Medical University, and written informed consent was obtained from all patients before cardiac catheterization procedures.

PCI procedures. The Allen’s test was performed routinely in all patients on both sides of wrists before PCI to evaluate the function of the palmer arch circulation between the radial and ulnar arteries. The operators were interventional cardiologists who had performed over 500 cases of TRI.

TRI was performed via the right radial artery in all patients of the TRI group. The right arm was positioned beside the patient’s body and the wrist hyper-extended. After local subcutaneous anesthesia with 1% lidocaine, the radial artery was punctured with a 20-gauge angiocatheter needle (Terumo), and a 0.635 mm (0.025˝) straight-tip guidewire (Abbott Laboratories) was inserted through the needle. Upon removal of the needle, a 16 cm, 6 Fr sheath (Terumo) was placed over the guidewire. A total of 200 μg nitroglycerin was administered through the sheath to prevent arterial vasospasm. Diagnostic angiography was performed using 4 Fr angiography catheters (Medtronic Inc). When the right radial artery failed to be the access, the left radial was selected to be an alternative approach.

In the case of the TFI group, the right femoral artery was punctured with an 18-gauge arterial needle after local anesthesia with 1% lidocaine and a 0.889 mm (0.035˝) guidewire was advanced through the needle. The procedure of diagnostic angiography was similar to the TRI group. When the right femoral failed to be the access, the left one was selected to be an alternative approach.

Angiographic results were evaluated by two independent cardiologists who were blinded to the procedures with the use of qualitative angiographic analysis. According to the result of angiography, PCI was performed unless the blood flow of IRA reached TIMI flow grade 3 and the residual stenosis of IRA was less than 75%. 

Anti-coagulant and anti-platelet regimen. All patients received clopidogrel (Sanofi-Aventis) 300 mg and aspirin (Bayer) 300 mg after the diagnosis of STEMI was established and intravenous thrombolysis was administered within 6 hours from symptom onset. Patients received heparin 5000 U bolus injection followed by an adjusted dose (800-1000 U/hour) to 24 hours after thrombolysis to maintain activated clotting time (ACT) 200-250 seconds. Additional heparin was administered if necessary during PCI. The use of the glycoprotein IIb/IIIa antagonist tirofiban (Wuhan Grand Pharmaceutical Group Co, Ltd) was left to the operator’s discretion during the PCI procedure. Tirofiban was administered with a 10 μg/kg bolus intravenous injection for 3 minutes followed by 0.15 μg · kg-1· min-1 infusion for 12 hours. The other medications were administered to the patients (including diuretics, intravenous vasodilator, lipid-lowering, beta-blockade, and angiotensin-converting enzyme inhibitors) according to current best practice.

Vascular access-site hemostasis. In the TRI group, the arterial access sheath was removed immediately and hemostasis was achieved following a tourniquet for 4-6 hours. While in the TFI group, the arterial access sheath was removed when ACT had fallen below 180 seconds. Hemostasis was achieved by manual compression for 20 to 30 minutes followed by a pressure bandage for 8 to 12 hours.

Endpoints and definitions. Endpoints were recorded from the admission to discharge from hospital. Several time intervals were measured in this study: puncture time, cannulation time, and total procedure time. The puncture success rate and time between PCI and ambulation were assessed. The vascular access-site complications were also assessed after the PCI procedure, including minor bleeding, major bleeding, pseudoaneurysm, and artery occlusion.

According to the TIMI classification, major vascular access-site bleeding was defined as a hemoglobin loss of at least 2 g/L, the administration of a blood transfusion, vascular repair, or prolonged hospitalization, but minor vascular access-site bleeding was defined as hematoma formation (hematoma <5 cm in diameter) not requiring specific therapy.¹⁵

The incidence of in-hospital MACE was observed. MACE was defined as death, recurrent myocardial infarction, and repeat target vascular revascularization (TVR).

Statistical analysis. The sample size calculation was determined using the estimation of differences in the incidence of bleeding complications between the two groups. The sample size was selected to demonstrate a 10% incidence of bleeding complications in the TFI group and a 3% incidence of bleeding complications in the TRI group.16 Using a 2-sided chi-square test and a significance level of P<.05, a total sample size of 90 patients (45 in each group) would provide 80% power to detect the difference with an alpha level of 0.05. A sample size of 108 patients (54 patients in each group) was planned, taking into account the likelihood of incomplete data collection, protocol violations, and patients lost to follow-up (estimated 20% total).

Continuous variables are expressed as mean ± standard deviation and are compared using the unpaired t-test for normally distributed and Mann-Whitney U-test for non-normally distributed variables. Categorical variables are expressed as absolute or relative frequencies and are compared using chi-square analyses or the Fisher exact test, as appropriate to the cell frequencies. Values of P<.05 were considered statistically significant. SPSS 17.0 for Windows (SPSS Inc) was used for statistical analysis.

Results

Baseline characteristics. A total of 119 cases were enrolled, with 60 cases randomly assigned to the TRI group and 59 cases to the TFI group. During this period, a total of 1260 PCIs were performed in our hospital. The baseline clinical characteristics of the patients are summarized in Table 1. Mean age, gender, history, and risk factors were similar in both groups. There were no stastical differences in cardiac function Killips classification, infarct location, and medication therapies between the two groups (all P>.05).

Time frame of procedures. The time frame of procedures of the patients is shown in Table 2. There were no significant differences in transfer time, time from emergency room to catheter lab, and total procedure time. Although the puncture time in the TRI group was a little longer, no significant difference was found, and the successful rates of puncture were similar between the two groups (both P>.05).

Angiographic and procedural characteristics. There were 4 cases in the TRI group and 1 case in the TFI group whose puncture site was changed, and all cases received PCI successfully. There were no significant differences in blood flow of IRA, number of stent(s), or length and diameter of stents between the two groups after PCI procedure (all P<.05; Table 3).

Post-PCI characteristics. Time between PCI and ambulation in the TRI group was much shorter than in the TFI group (22.18 ± 5.37 hours vs 28.92 ± 6.14 hours; all P<.001). There was a trend toward lower incidence of bleeding complications, vascular complications, and in-hospital MACE. The levels of serum creatinine (SCr) and hemoglobin (Hb) after PCI were a little lower in the TFI group, but without significance (Table 4).

Discussion

Early and complete reperfusion in the setting of STEMI, which includes thrombolysis, primary PCI, and CABG, is effective in limiting left ventricular damage and improving clinical outcomes.^17-19 Primary PCI has been accepted as the strategy for reperfusion providing best outcomes in STEMI patients because of the advantages of minimal invasion, completely patency of IRA, limiting infarction size, and improving outcomes.¹⁴ However, the efficacy of this therapy is time dependent and several barriers limit its use. Therefore, intravenous thrombolytic therapy is still an established, simple, widely available, and cost-effective treatment option for STEMI, especially for patients who are admitted in non-PCI hospitals. Up to now, ACC/AHA guidelines still list thrombolytic therapy as a class I indication.²⁰ According to current guidelines, coronary angiography 3-24 hours after thrombolysis is required for patients who are admitted in non-PCI hospitals and first received intravenous thrombolysis.²¹ In this study, the STEMI patients who received routine early PCI within 12 hours after thrombolysis were enrolled, and the results found that early PCI following thrombolysis could improve the coronary flow of IRA and myocardial perfusion.

The risk of bleeding complications during PCI may increase under anti-platelet and anti-coagulation therapies. PCI-related bleeding, in the setting of primary PCI for STEMI patients, particularly occurs mainly at the arterial puncture site and is consistently associated with a much higher risk of death during clinical follow-up, as reported in many contemporary pharmacoinvasive trials and registries.²² Lots of studies^23,24 have shown the advantages of TRI, particularly in the patients who were at high risk of vascular complications. However, there are few reports on the safety and feasibility of early TRI in STEMI patients who have received thrombolysis. To our knowledge, this is the first randomized study focusing on the safety and feasibility of TRI in STEMI patients following intravenous thrombolysis. The results showed that despite being a limited-sized study, there was a trend toward lower incidences in hospital death, bleeding, and hematoma formation. This is consistent with several recent studies that have found a similar trend or statistically significant differences between TRI and TFI.^25,26

One definite advantage of TRI is the reduction in vascular complications, especially access-site related complications such as hematoma, pseudoaneurysm, and arterioveneous fistula when aggressive anti-coagulation and anti-platelet therapies are sought. This can be explained by the fact that the femoral artery usually runs deep under the skin close to the femoral vein and nerve.9 The radial artery offers the unique feature of being very superficial, and is thus easy to puncture and easy to compress. In addition, no major nerves or veins are located near the artery, minimizing the risk of injury of these structures. The above is the anatomic basis of TRI.

In this study, 4 cases received PCI via left radial or ulnar artery because of failure in right radial artery approach. However, no differences of procedural time were found. Accessing the radial artery is technically more challenging and more time-consuming than the femoral access route, as well as exposure time.

Our previous study has found that the quality of images was similar in CAG with either 4 Fr or 6 Fr catheters.²⁷ In this study, 4 Fr catheters were used in CAG in both groups, and the results shows that the use of 4 Fr catheters in CAG could minimize the injury of route, as well as reduce the volume of contrast medium and increase the success rate of TRI.

Study limitations. This study was a small-sized trial that only observed the MACEs in hospital. In addition, we excluded cardiogenic shock with STEMI from this study, due to the fact that hypotension would have precluded the use of vasodilators, used in the radial artery cocktail, forcing the operators to choose transfemoral access, and hence introducing a selection bias.

Conclusion

The present study suggested that TRI for STEMI patients following intravenous thrombolysis was as safe and feasible as TFI, and has fewer vascular access-site complications compared to TFI when performed by experienced operators. Future studies need to consider a large multi-center randomized trial or subgroup analysis of the registry studies to confirm this conclusion.

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From the Department of Cardiology, Second Hospital of Hebei Medical University, Shijiazhuang, PR China.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted December 28, 2011, provisional acceptance given January 27, 2012, final version accepted March 23, 2012.
Address for correspondence: Dr Xiang-hua Fu, Department of Cardiology, Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang 050000, PR China. Email: fuxh999@hotmail.com