Predictors and Outcomes Associated With Radial Versus Femoral Access for Intervention in Patients With Acute Coronary Syndrome in a Real-World Setting: Results From the Acute Coronary Syndrome Israeli Survey (ACSIS) 2010

Abstract: Background. Use of transradial intervention (TRI) is becoming more popular, and recent studies suggest an advantage for TRI in high-risk patients presenting with acute coronary syndrome (ACS). The aim of our study was to describe current utilization and outcomes of transradial intervention (TRI) in real-world patients presenting with ACS.  Methods. Data were derived from the ACS Israeli Survey (ACSIS 2010), a nationwide prospective survey of patients presenting with ACS over a 2-month period. Follow-up was continued for up to 1 year. Results. Of 1815 ACS patients undergoing coronary angiography, 613 (34%) underwent TRI, which was more likely to be employed among patients with lower-risk characteristics. Patients undergoing TRI had significantly lower 30-day mortality and in-hospital bleeding. On multivariate analysis, the risk of in-hospital major bleeding was reduced by 60% in patients undergoing TRI (P=.04). However, no significant differences in other components of major adverse cardiac events or mortality were demonstrated at 30 days. All-cause mortality at 1 year was significantly lower among patients who underwent TRI. However, after multivariate adjustment, this effect was no longer significant. Conclusions. In our study of real-world patients, better TRI outcomes are related largely to lower baseline risk of patients allocated to this approach, suggesting that TRI may be underutilized in high-risk ACS patients.  

J INVASIVE CARDIOL 2014;26(8):398-402

Key words: PCI, radial approach, acute coronary syndrome 

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Campeau in 1989¹ and subsequently Kiemeneij and Laarman in 1993² successfully attempted diagnostic cardiac catheterization and percutaneous coronary intervention (PCI), respectively, using the radial artery. Since these seminal reports, the use of transradial intervention (TRI) has gradually gained acceptance. Support for this practice has stemmed from numerous small trials and observational studies that have shown advantages of TRI over transfemoral intervention (TFI) with respect to early ambulation, shorter hospital stay,³ fewer access-site vascular complications,⁴ fewer major hemorrhages, and less need for transfusions.⁵ Recently, the RIVAL trial randomized 7021 patients undergoing angiography due to acute coronary syndrome (ACS) to radial versus femoral access. While in all ACS patients, use of TRI did not show any major benefit on major bleeding, major adverse cardiac event (MACE) rate, or mortality, the investigators did observe a benefit of the radial approach in patients with ST-segment elevation MI (STEMI), as well as in centers that perform a high volume of procedures via the radial artery.⁶

Worldwide, there is much variability in the use of TRI among countries and among centers within each country. While in some European countries, TRI is now the preferred route to perform cardiac catheterization and percutaneous coronary intervention (PCI),⁷ only a small minority of procedures are performed using the radial route in the United States.⁸

Over the last decade, the use of TRI in Israel has grown in popularity to the extent that about one-third of all coronary procedures are performed using the radial approach. Using data from the Acute Coronary Syndrome Israeli Survey (ACSIS) 2010, a nationwide survey including all patients admitted with the diagnosis of ACS during a 2-month period, we set out to describe current practice, factors associated with the use of the radial approach, and outcomes of patients undergoing intervention using the radial approach in a real-world setting. 

Methods

Study population. Patients were derived from the ACS Israeli Survey (ACSIS 2010), a nationwide survey conducted during March and April of 2010 in all 25 coronary cardiac units and cardiology wards operating in Israel. On-site coronary catheterization with percutaneous intervention and coronary bypass graft facilities were available in 23 and 12 of the centers, respectively. Demographic, historical, and clinical data were recorded on prespecified forms for all patients admitted with the diagnosis of ACS. Patients were managed at the discretion of each center. Decision to perform angiography by the radial or femoral route was at the discretion of each performing operator. Route of arterial access used to complete the procedure was recorded prospectively on prespecified forms. All patients were either seen or contacted by telephone at 30 days. Mortality at 30 days was determined for all participants from hospital charts and by matching the identification numbers of the patients with the National Population Registry. Mortality at 1 year was ascertained by matching the identification numbers of the patients with the National Population Registry. Of the 2193 patients with ACS recruited during the study period, 1815 patients (83%) underwent coronary angiography and intervention as indicated, and comprised the present study population. 

Data collection and endpoints. Diagnosis of myocardial infarction was based on the Universal Definition of Myocardial Infarction.⁹ ST-elevation ACS was based on the presence of ST-elevation ≥1 mm in ≥2 contiguous leads, typical anginal-type discomfort, and a rise in serum biomarkers (cardiac specific troponins and/or CK-MB).

A primary composite endpoint of the present study included the occurrence of major adverse cardiac event (MACE) at 30 days (comprising death, recurrent ACS, stent thrombosis, and hospitalization for heart failure) and 1-year mortality. Stent thrombosis was diagnosed in accordance with the Academic Research Consortium (ARC) definition for definite or probable stent thrombosis.¹⁰

 In addition, major bleeding (defined as bleeding with an associated drop in hemoglobin of 5 g/dL or a drop in hematocrit of 15%, any intracranial or retroperitoneal bleeding, or need for transfusion of ≥2 units of packed cells) was assessed as a secondary endpoint.

Statistical analysis. Statistical analysis was performed using SAS software, version 8.2 (SAS Institute, Inc). Continuous variables are presented as mean ± standard deviation or median and interquartile range, and categorical variables are expressed as percentages. Continuous variables were compared with the Student t-test if data followed a normal distribution and with the Wilcoxon Rank sum test if data were skewed. Categorical variables were compared using chi-square test or Fisher’s exact test when indicated. 

Multivariate logistic regression analysis was used to identify independent predictors for a radial versus femoral approach from candidate covariates listed in Table 1. A stepwise selection method was used with a significance level of 0.05 for entering and removing an explanatory variable.

Multivariate logistic regression analysis was used to assess the benefit of radial versus femoral approach for reducing the 30-day MACE and major bleeding endpoints, and multivariate Cox proportional hazards regression modeling was used to assess 1-year mortality. All multivariate models included the following prespecified variables: age, gender, diabetes mellitus, past myocardial infarction, Killip class, use of glycoprotein IIb/IIIa antagonists, time from symptom onset to admission (≤3 hours, >3 hours), door-to-balloon time (≤90 min, >90 min), multivessel coronary disease, and pretreatment with clopidogrel. To account for a possible selection bias for mode of vascular access, a propensity score was calculated by logistic regression analysis including the following variables: age (continuous), gender, hypertension, diabetes mellitus, dyslipidemia, family history of coronary artery disease, current or past smoking, prior stroke, congestive heart failure (CHF), peripheral vascular disease, prior PCI or coronary artery bypass grafting, antecedent angina, chronic renal failure, mode of transportation (mobile intensive cardiac care unit vs other), time from symptom onset to arrival, heart rate, systolic blood pressure, Killip class ≥2, infarct location (anterior vs non-anterior), and chronic aspirin treatment. This score ranged from 0.12-0.92. This model yielded a C-statistic of 0.74. All tests were 2-sided, and values of P<.05 were considered statistically significant.

Results

Of the 1815 ACS patients who underwent coronary angiography during the study period, a total of 613 (34%) were performed by the radial route and 1189 (66%) by the femoral route. The baseline characteristics of patients undergoing coronary angiography are shown in Table 1. Compared with patients undergoing TFI, patients undergoing TRI were slightly younger, less likely to have had previous coronary bypass grafting, and more likely to present in Killip class I. They also presented with smaller infarcts, as evidenced by a lower incidence of cardiogenic shock during their hospital course, lower incidence of left ventricular ejection fraction (LVEF) <40%, and lower incidence of developing Q-waves on the discharge electrocardiogram (ECG). In addition, patients undergoing primary PCI by the femoral route were more likely to present with an occluded infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] 0-1 flow) on initial angiography and were slightly more likely to undergo angioplasty and receive glycoprotein IIB/IIIA antagonists. There were no major differences in other clinical variables, including body mass index, presence of diabetes, renal failure, or prior cerebrovascular disease. The baseline and infarct characteristics of patients with ST-elevation ACS and non-ST elevation ACS undergoing coronary angiography by the femoral or radial route are included in Appendix 1 and show findings consistent with those in the total population.  

Predictors for TRI in ACS patients. Multivariate logistic regression modeling was used to identify factors independently associated with the use of radial vs femoral approach among study patients (Table 2). This analysis showed that TRI was more likely to be employed among ACS patients who displayed lower risk characteristics: LVEF >40% was associated with a significant 76% greater likelihood for a radial approach (P<.001), whereas patients who presented with STEMI were less likely to undergo coronary angiography with a radial approach compared to those who presented with non-ST elevation myocardial infarction (NSTEMI). In addition, TRI was less likely to be employed in patients who underwent prior coronary artery bypass graft and more likely to be employed among those who underwent prior PCI (Table 2). Notably, a younger age was not identified as an independent predictor for TRI after multivariate adjustment (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.88-1.75; P=.22). The distribution of radial procedures between the different centers in the survey is shown in Figure 1. Much variation existed between centers, and center volume (upper volume tertile centers marked with an asterisk) was not necessarily associated with greater proportion of radial procedures. 

Outcomes associated with radial vs femoral approach in ACS patients. Univariate outcomes at 30 days are shown in Figure 2. Patients undergoing TRI had significantly lower 30-day mortality and in-hospital bleeding. On multivariate analysis, after adjusting for multiple confounders, the risk of in-hospital major bleeding was significantly reduced by 60% in patients undergoing TRI as compared with those undergoing TFI (odds ratio [OR], 0.4; CI 95%, 0.164-0.980; P=.04). However, no significant differences in other components of MACE or mortality were demonstrated at 30 days. Similar results were shown in the multivariate models that included a propensity score for TRI. 

Kaplan-Meier analysis showed that the cumulative probability of all-cause mortality at 1 year was significantly lower among patients who underwent TRI as compared with TFI (Figure 3A). However, after multivariate adjustment, the effect of radial vs femoral approach on 1-year mortality was not statistically significant (HR, 0.94; 95% CI, 0.81-1.19; P=.54) (Figure 3B). A secondary analysis in which all multivariate models were further stratified by center was performed. These analyses yielded similar results. The effect of TRI vs TFI on all outcomes was similar between patients with STEMI and NSTEMI (all P-values for “TRI by MI type” interactions were >.10).

Discussion

The major findings of our study are that: (1) among ACS patients in a real-life setting, significant differences exist in patients selected for TRI as compared with TFI. Specifically, current real-world practice is to underutilize the radial approach in higher-risk patients, including those with STEMI and a lower ejection fraction on admission; and (2) patients undergoing TRI have lower rates of in-hospital major bleeding, but do not differ with regard to rates of MACE or adjusted mortality at 30 days or 1 year. 

Over the last decade, the radial access route has gained much popularity in Israel. Over 30% of ACS cases underwent TRI in our study. Since this was not a randomized trial, vascular access was obtained at operator discretion. The vast majority of active operators in Israel are dedicated interventional cardiologists; thus, most TRI cases in this registry were performed by operators proficient in this technique and outcomes in this group are unlikely to be affected by a radial learning curve. There was a definite bias regarding patient selection for TRI, with “sicker” and older patients with large myocardial infarctions less likely to undergo TRI. While patients were not randomized to a treatment modality, it is notable that even among experienced radial operators, sicker patients were less likely to undergo TRI. Similar findings regarding patient selection for TRI were reported in a large registry of STEMI patients undergoing PCI in Italy.¹¹ Similar to our study, about one-third of the patients underwent TRI and patients in this Italian registry were also younger with higher prevalence of previous myocardial infarction, cardiogenic shock, lower LVEF, and lower prevalence of previous CABG. Outcomes were assessed using propensity-matched pairs that demonstrated decreased 2-year mortality rates and decreased need for transfusion. 

In the present study, TRI was associated with a significant reduction in major bleeding events, but was not associated with a statistically significant effect on additional outcomes, including 30-day MACE and 1-year mortality. Variable outcomes of TRI have been reported in the literature. In the previously mentioned Italian registry of TRI in STEMI patients, Valgimigli et al assessed outcomes using propensity-matched pairs. Using this method, they were able to demonstrate decreased 2-year mortality rates and decreased need for transfusion.¹¹ In a recently published meta-analysis of 10 randomized studies comparing TRI vs TFI in STEMI patients undergoing PCI, TRI was associated with lower short-term mortality. However, in this meta-analysis only a non-significant trend toward less major bleeding was found.¹² An earlier meta-analysis of 23 randomized trials comparing TRI with TFI included 7020 patients with a wide spectrum of indications for angiography, and found a 73% reduction in the incidence of major bleeding but only a trend for reduction in ischemic events and death.³ The largest randomized controlled study of TRI in patients with ACS, the RIVAL study, was recently published by Jolly et al,⁶ and randomized 7021 patients to TRI and TFI. Similar to the present findings, this well-conducted, large, randomized trial showed no differences in major outcomes. However, more favorable outcomes were reported for STEMI patients undergoing TRI in centers with high TRI volume.¹³ Results from the RIVAL study suggest that STEMI patients have a unique potential to benefit from TRI. Indeed, a recent study found that vascular access site followed hemodynamic instability and age in terms of effect on mortality risk (OR, 5.2; 95% CI, 2.8-0.66).¹⁴ In this context, our findings regarding underutilization of TRI in STEMI patients in a real-world setting are significant. Increased use of TRI in ACS patients may help improve clinical outcomes and reduce major bleeding events.

The major weakness of our study is its non-randomized nature and relatively short data collection period of 2 months, which might not accurately reflect current practice. In addition, certain data were not collected, including femoral sheath size, use of femoral closure devices, or data on crossovers from TRI to TFI or vice versa, which might have impacted the risk of bleeding. However, the strength of our data is that it reflects current practices by experienced interventional cardiologists in non-selected ACS patients in a real-world setting. 

Conclusions

Our data, derived from a real-world setting of ACS patients, suggest that the favorable outcomes seen with TRI are largely related to the lower baseline risk of these patients, suggesting that TRI may be underutilized in high-risk ACS patients who may derive greater benefit from this approach. Further data on high-risk ACS patients are needed.   

References

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From the ¹Chaim Sheba Medical Center, Tel Hashomer, Israel; ²Shaare Zedek Medical Center, the Hebrew University School of Medicine, Jerusalem, Israel; ³Soroka Medical Center, Beer Sheva, Israel; and ⁴Rabin Medical Center, Petach Tikva, Israel.

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 August 26, 2013, provisional acceptance given November 4, 2013, final version accepted February 3, 2014.

Address for correspondence: Paul Fefer, MD, Heart Center, Chaim Sheba Medical Center, Tel Hashomer, Israel 52621. Email: paulfefer@gmail.com