Analysis of patients submitted to percutaneous coronary intervention via radial artery access . The SAFIRA Registry database

Background: The choice of the radial access for performing percutaneous coronary interventions has grown due to evidence of the greater benefits of the technique, such as reduced vascular complications, lower bleeding rates, early ambulation, shorter hospital stay and lower costs. The present study aimed to analyze patients submitted to percutaneous coronary intervention using the radial access in comparison to the femoral artery access in elective cases or in acute coronary syndromes. Methods: An observational, single center study based on the SAFIRA registry database, which includes patients undergoing percutaneous coronary intervention with drug-eluting stents. The primary endpoint was the incidence of cardiovascular mortality in a 3-year follow-up. Results: A total of 2,453 patients were included, 1,237 of which allocated to the radial group and 1,216 to the femoral group. The prevalence of vascular complications was higher in the femoral group (OR: 15.4; p=0.008), as was the contrast volume used (OR: 1.001; p=0.02). The primary endpoint of cardiovascular mortality in the femoral group was 4.5% vs. 2.3% in the radial group (RR: 1.77; p<0.01). All-cause mortality rates (10.2% vs. 7.4%, RR: 1.37; p=0.03) and major adverse cardiac event rates (12.2% vs. 8.9%, RR: 1; 36; p<0.01) were also higher in the femoral group. When adjusted for relevant clinical variables, the femoral access remained as an independent predictor of cardiovascular mortality. Conclusions: Radial access was effective in reducing mortality, major adverse cardiac events and vascular complications among patients undergoing percutaneous coronary intervention. Descriptors: Percutaneous coronary intervention; Radial artery; Femoral artery. Como citar este artigo: Silva BS, Mangione FM, Wili LF, Mauro MF, Cristóvão SA, Mangione JA. Análise dos pacientes submetidos à intervenção coronária percutânea por via radial. Dados do Registro SAFIRA. J Transcat Interven. 2018;26(1):eA0018. https://doi.org/10.31160/ JOTCI2018;26(1)A0018 Autor correspondente: Bruno Stefani Lelis Silva Avenida Salvador Markowicz, 135 sala 709 − Santa Helena CEP: 12916-400 − Bragança Paulista, SP, Brasil E-mail: brunostefanimed@gmail.com Recebido em: 30/1/2018 Aceito em: 11/10/2018 1 Hospital Universitário São Francisco na Providência de Deus, Bragança Paulista, SP, Brasil 2 Hospital Beneficência Portuguesa de São Paulo, São Paulo, SP, Brasil


INTRODUCTION
The radial artery access for percutaneous coronary intervention (PCI) began to be used in 1992. 1,2Among its advantages are the anatomical location for puncture, easy compression, early removal of the introducer, lower risk of vascular complications and earlier ambulation. 3,4Recent studies have shown reduction in mortality with the use of the radial artery access in patients presenting acute coronary syndrome. 5,6][9] The aim of the present study was to analyze patients submitted to PCI via radial access and compare it to femoral access patients, regarding all clinical presentations of coronary atherosclerotic disease.

METHODS
This is an observational, single center study, based on data from the Safety and Efficacy of Pharmacological Stents in a Real World Population registry (SAFIRA, http://www.scielo.br/pdf/rbci/v22n1/0104-1843-rbci-22-01-0023.pdf), which included consecutive patients that underwent PCI with drug-eluting stents, from July 2002 to August 2016.PCIs were performed according to the current recommendations and the vascular access was defined according to the clinical characteristics of patients, operator preference and arterial pulse amplitude.
The primary endpoint was cardiovascular mortality du ring a 3-year follow-up.Secondary endpoints analyzed were the following: all-cause mortality, acute myocardial in farction (MI), major adverse cardiac events (MACE), vascular complications, and volume of contrast.MACE comprised cardiovascular mortality, non-fatal acute MI or target vessel revascularization.Vascular complications included dissection, limb ischemia, compartment syndrome, pseudoaneurysm, arteriovenous fistula, or retroperitoneal hematoma.All deaths were considered cardiac, unless a noncardiac cause could be clearly established.Acute MI was diagnosed by proven abnormal blood levels of myocardial necrosis markers (creatine kinase -CKMB or troponin).
Data collection was performed using the SAFIRA Registry database, at the Hospital Beneficência Portuguesa de São Paulo, after approval by the Research Ethics Committee (protocol 778-12; CAEE: 00771112.9.0000.5483).All patients included in the study signed the Informed Consent Form.Clinical follow-up was performed by office consultation or telephone calls at 30 days, 6 and 12 months, and thereafter annually.

Statistical analysis
Categorical variables were expressed as absolute frequency and percentages, and compared using the Chi-square test.
Continuous variables were presented as mean and standard deviation and compared with Student's t test.Cumulative event-free survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test.
The multivariate Cox regression model included clinical variables that reached statistical significance in the univariate analysis (p<0.05).Interaction testing was used to investigate the potential impact of the clinical presentation (chronic vs. acute) at the primary endpoint.The proportional hazard hypothesis was tested using the Schoenfeld residuals test.A p-value <0.05 was considered significant.Statistical analysis was performed using the STATA 14 software package (StataCorp LP, USA).

RESULTS
A total of 2,453 patients were included, 1,237 in the radial group and 1,216 in the femoral group.The femoral group had a higher percentage of female patients (34.0% vs. 23.0%;p<0.001), a higher prevalence of chronic renal failure (9.9% vs. 6.7%;p<0.01), and of previous percutaneous or surgical coronary artery bypass graft (CABG) (20.0% vs. 16.0%,p=0.01, and 22.0% vs. 10.0%;p<0.01, respectively).A higher prevalence of patients with ST-elevation myocardial infarction (STEMI) in the group of patients treated through radial access (3.5% vs. 1.9%) was observed.Since the radial technique was introduced more recently, there was a higher rate of use of second-generation drug-eluting stents and new antiplatelet agents, such as prasugrel and ticagrelor (90.1% vs. 55.4%;p<0.01, and 10.8% vs. 6.7%;p<0.01, respectively) in this group.Baseline clinical characteristics and procedures are shown in Tables 1 and 2.
When adjusted for clinical variables that showed statistical significance in the univariate analysis (Table 4), femoral access remained an independent predictor of cardiovascular mortality, but it was no longer a predictor for all-cause mortality and MACE (Table 5).The clinical presentation did not alter the relation between type of vascular access and cardiovascular mortality (interaction p=0.94), indicating a significant benefit for using the radial access, both for stable clinical presentation and ACS.

DISCUSSION
The present study has shown that the radial artery access reduced cardiovascular mortality rate, regardless of clinical presentation, showing a positive impact, both in the ACS scenario and for patients with stable coronary artery disease.We also observed the radial vascular access to be safer, with reduction in vascular complications and total contrast volume.
Radial artery access has been consolidated as the preferred option in patients submitted to PCI in recent years.Since the introduction of the technique, the development and improvement of materials, associated with the greater operator's experience, have made its results as effective as other vascular accesses (femoral puncture and brachial dissection). 10,11 e RIFLE (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) study was conducted in four centers in Italy, comparing patients with STEMI. 5Similar to the findings observed in the present study, there was a lower rate of MACE and bleeding associated with the procedures performed via radial access.There was a reduction in cardiac mortality (9.2% in the femoral group vs. 5.2% in the radial group; p=0.02), and a 47% reduction in the rate of vascular complications related to the access route (6.8% femoral vs. 2.6% radial; p=0.002).The crossover rate of radial access to the femoral one was 4.7%, similar to the present registry.
The RIVAL (Radial Versus Femoral Access for Coronary Angiography and Intervention in Patients with Acute Coronary Syndromes) study, likewise, included only ACS patients and showed no difference in their primary MACE endpoint (3.7% in the radial vs. 4.0% in the femoral group; p=0.50). 6However, there was a significant reduction in the number of severe vascular complications (1.4% in the radial group vs. 3.7% in the femoral group; p=0.0001).On the other hand, the crossover rate of the radial to femoral access was 7.6%.Subgroup analysis showed a significant reduction in the primary endpoint in centers with greater expertise in performing procedures by the radial route (>142 procedures per operator/year), corroborating the data of the present study, which was performed in a center with vast experience in the technique.
MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX), a randomized multicenter study, was published in 2015 and included 8,404 patients with ACS with and without ST segment elevation. 12In the study, patients undergoing PCI via radial artery showed significantly lower rates in the endpoint that comprised death, acute MI, stroke and major bleeding, mainly due to the 33% relative reduction in the bleeding rate according to the Bleeding Academic Research Consortium (BARC) criteria.There was also a reduction by 28% in all-cause mortality rate (1.6% vs. 2.2%; RR: 0.72; 95%CI 0.53-0.99;p=0.045).
Unlike the studies cited, in the present registry the majority of patients had stable angina (77%) and since there was no interaction between the clinical presentation and the primary endpoint of cardiovascular mortality, it is possible to consider that the benefits of radial access are also evident in this scenario.A similar result was found in a single center study performed at the Instituto Dante Pazzanese de Cardiologia, in São Paulo, from 2007 to 2012, where 72.6% of patients had stable coronary artery disease and radial access was associated with a reduction in the risk of vascular complications when compared to the femoral access.

CONCLUSION
The radial artery access was effective in reducing cardiovascular mortality, all-cause mortality, major adverse cardiac events and vascular complications in patients undergoing percutaneous coronary intervention with drugeluding stents.After adjustment for relevant clinical factors, the femoral artery access remained as an independent predictor of cardiovascular mortality.

Figure 1 .
Figure 1.Kaplan-Meier curve for cardiovascular death stratified by vascular access.

Figure 2 .
Figure 2. Kaplan-Meier curve for all-cause death stratified by vascular access.

Figure 3 .
Figure 3. Kaplan-Meier curve for major adverse cardiac events stratified by vascular access.

Table 2 .
Clinical presentation and procedure characteristics

Table 3 .
Clinical endpoints according to vascular access after 3 years

Table 5 .
Multivariate analysis for clinical events