Follow-Up of Patients Undergoing Early Invasive Strategy by the Transradial or Transfemoral Approach with Vascular Closure Device

The early interventionist strategy represents an important step in the treatment of non-ST segment elevation myocardial infarction (NSTEMI), due to its superiority in reducing death and reinfarction when compared to the conservative strategy.1 Since the completion of invasive coronary procedures undergoing therapy Intense antithrombotic therapy predisposes to the occurrence of severe bleeding, with a potential prognostic impact, strategies aimed at preventing this complication guide the contemporary management of this patient profile.2 In this context, the option for radial access, in detriment to the femoral one, has been shown to reduce mortality and severe bleeding rates, especially after obtaining proficiency with the technique.3 In turn, the efficacy and safety resulting from the adoption of vascular occlusion devices (VOD) in the prevention of complications in procedures carried out through the 299 International Journal of Cardiovascular Sciences. 2017;30(4):299-306

lower limb is still a matter of debate. 4In the randomized clinical trial Angio-Seal versus the Radial approach in acute coronary syndrome (ARISE) the systematic use of a VOD in patients undergoing invasive stratification by femoral access was shown to be not inferior to radial access with respect of the incidence of vascular complications related to the arterial puncture site at 30 days. 5e objective of the present pre-specified analysis of the ARISE study was to compare the incidence of serious adverse cardiovascular events in clinical follow-up of 12 months, according to the access route adopted.

Methods
The design and rationale of the ARISE pilot study has been previously published. 6In summary, from July 2012 to March 2015, 240 patients with a diagnosis of NSTEMI who underwent invasive stratification were randomized to perform the procedure by radial access or femoral vein with VOD Angio-Seal (St.Jude Medical, St. Paul, Minnesota, US).The choice of Angio-Seal relied on the ease of handling, lower cost and greater casuistry published in the literature in its favor.Patients should present at least two of three markers of greatest clinical severity: ischemic changing in 12-lead electrocardiogram, positivity of biomarkers of myocardial necrosis or more than 60 years age.The objective of this analysis was to compare the techniques for free survival of serious adverse cardiovascular events at 12 months, defined as general mortality, acute myocardial infarction (AMI) or cerebrovascular accident (CVA).

Study procedures
For the randomization process an aleatory sequence was obtained through computational algorithms and maintained in individual envelopes, allowing allocation concealment.The coronarography, by both, radial and femoral accesses, was performed using the Judkins technique, using arterial introducers with 6 French diameter.Percutaneous coronary intervention (PCI) was indicated when a lesion was determined as a culprit lesion of the clinical event, with a severity of stenosis diameter ≥ 70%, showing a high probability of angiographic success, being performed immediately after the end of coronary angiography and left ventriculography (ad hoc) .Anticoagulation in the hemodynamic laboratory was obtained with intravenous 85-100 U / kg unfractionated heparin, suited to prior subcutaneous administration of enoxaparin or fondaparinux.In order to obtain haemostasis in the radial technique, the TR BAND radial compression device (Terumo Corporation, Tokyo, Japan) was applied, according to a protocol previously validated by our center, aiming at maintenance of patent anterograde flow. 7In the femoral technique, The VOD Angio-Seal, preceded by the systematic accomplishment of femoral angiography and maintaining absolute rest in the bed for 60 minutes after achieving adequate hemostasis.The success of the device was defined as the obtaining the adequate hemostasis at the end of the procedure, without the need to apply other compression methods.
Markers of myocardial necrosis, hemoglobin and hematocrit were measured pre-procedure and between 12 and 24 hours after its completion.Electrocardiogram was performed soon after the procedure or before the suspicion of a new ischemic event.Vascular complications related to arterial access were evaluated during hospitalization and on-site visit in 30 days after the procedure.The late assessment of the occurrence of cardiovascular events was obtained through telephone contact at six and twelve months, as well as by electronic chart review.

Statistical analysis
Absolute and relative frequencies were presented for the categorical and numerical variables, summarymeasures (mean and standard deviation).The existence of associations between two categorical variables was verified using the chi-square test, or alternatively in cases of small samples, Fisher's exact test.The comparison of means between two groups was performed using Student's t-test for independent samples.The survival function free of serious adverse cardiovascular events (death, AMI or CVA) was estimated by the Kaplan-Meier model and compared using the log rank test (Mantel-Cox).A significance level of 5% was used for all statistical tests.Statistical analyzes were performed using the statistical software SPSS 20.0.
The study was approved by the local research ethics committee and a free and informed consent form was obtained from every participant.There was no source of external funding and the authors are entirely responsible for the design, conduction, data analysis and final drafting of the manuscript.

Results
Figure 1 illustrates the inclusion and randomization flowchart of the study.The mean age was 63 years, 30.8% were diabetic, troponin positive was detected in 84.2% of the sample and, except for the greater prevalence of women in the radial group, no differences were observed between the groups (Table 1).65% of the evaluated sample was classified as low or very low risk for bleeding from the CRUSADE score.PCI was performed in 86.7% of the cases and the characteristics of the procedures are expressed in Table 2. Stents were implanted in 97.6% of the cases, with predominance of non-pharmacological stents due to public health system reimbursement policies.
Angiographic and procedural success rates were high (97.6% and 95.2%, respectively).Hemostasis with TR BAND was obtained in 100% of the procedures by radial access, with anterograde flow demonstrated by the oximetric curve in 102 patients (85%).In six (5%) patients in the femoral group, the Angio-Seal device was not sufficient to obtain hemostasis, requiring additional manual compression for a period longer than 10 minutes.The rate of vascular complications at the 30-day arterial puncture site was 12.5% in the Angio-Seal group, at the cost of hematomas > 5 cm, and 13.3% in the radial group, at hematomas > 5 cm (6.7%) and asymptomatic occlusion of the radial artery (5.8%), with no significant difference.There were no cases of arteriovenous fistula, retroperitoneal hematoma, compartment syndrome, limb ischemia, nerve damage or the need for repairing vascular surgery.
The ischemic endpoints after 1 year according to the used access via are expressed on Table 3.The rate of severe bleeding or blood transfusion was 2.5% in the Angio-Seal group and 1.7% in the radial group (p = 1,000).Figure 2 illustrates the free survival curve of serious adverse cardiovascular events compound at 12 months, with no distinction being made between techniques (90.8% versus 94.2%, p = 0.328).

Discussion
The approach of NSTEMI contemplates invasive risk stratification risk and potent antithrombotic pharmacotherapy, a strategy that promotes the reduction of ischemic adverse events at the expense of increased bleeding risk.In this scenario, the adoption of the radial technique as an alternative to the femoral technique was shown to be superior in the reduction of vascular complications related to the arterial puncture site and consequently of clinical outcomes. 8Encouraging results from unicentric studies with modest sampling were corroborated by large randomized meta-analyzes.Reviewing the data from patients with acute coronary syndrome conducted in a meta-analysis of 17 studies and 19,328 procedures, radial access promoted a significant reduction of 27% in mortality and 40% in severe bleeding. 9Including all spectra of the atherosclerotic coronary disease, meta-analysis with 22,843 participants maintained the observed benefit with reduction of 29% in total mortality and 47% reduction in severe bleeding. 10wever, femoral access still prevails as a preferential route for the accomplishment of invasive coronary procedures.In Brazil, it is estimated that the use of the radial technique in PCI make up currently about 30% of the cases. 11,12Thus, it is imperative to adopt measures able to provide greater safety to the procedure, such as reducing the diameter of the devices endovascular, early removal of the arterial introducer, fluoroscopy or ultrasound guided femoral puncture.On the other hand, the use of DOV in obtaining haemostasis by the femoral technique shows conflicting data about its efficacy, supported mainly by negative studies involving first generation devices, many of which are no longer commercialized. 13,14However, contemporary analyzes indicate superiority Strategy against manual compression.Among 85,048 ICPs performed between 2007 and 2009, registered in a multicenter registry in the state of Michigan, of which 28,528 used a DOV, they promoted a significant reduction of vascular   complications and the need for transfusion. 15The British national real-world registry encompassing 271,485 therapeutic procedures performed between 2006 to 2011 showed a lower 30-day DOV-favorable mortality rate, especially among women, acute coronary syndrome as a form of clinical presentation and recent thrombolysis. 16e main question still open is whether the DOV present the same effectiveness of the radial technique in the reduction of vascular complications and bleeds related to the access route.The ARISE study adds data to this questioning, since it is the first randomized clinical trial comparing the two strategies in a population of patients with SIMISSST.No differences were observed between the techniques regarding the incidence of vascular complications at 30 days and serious adverse cardiovascular events at 12 months.In fact, it is postulated that the benefits derived from the radial technique are mainly due to the reduction in the prevalence of severe bleeding and the need for blood transfusion, 17 which was not observed in our study.Our findings differ from the few publications comparing the radial access to VOD, where the first is associated with a significant reduction of vascular complications, as the main difference

Figure 1 -
Figure 1 -Inclusion and randomization flowchart of the ARISE study.

Figure 2 -
Figure 2 -Probability of death, acute myocardial infarction or stroke-free survival at 12 months according to the access route adopted.