The Association Between the Transradial Approach for Percutaneous Coronary Interventions and Bleeding

ABSTRACT: Bleeding complications after percutaneous coronary interventions (PCI) are a significant clinical problem associated with worse patient outcomes, including mortality. A number of studies have demonstrated that the majority of bleeding complications in patients undergoing PCI are related to access-site bleeding. Employing the transradial artery approach to PCI markedly reduces these bleeding rates. The reductions in bleeding and transfusions from employing the transradial approach may be associated with improved survival in PCI patients. Despite these data, the prevalence of transradial PCI remains low and its adoption by operators has been slow to increase. Growing data to support the superior clinical outcomes with radial artery PCI, coupled with improved awareness of this data, may lead to increases in its adoption and improved clinical outcomes and mortality after PCI. J INVASIVE CARDIOL 2009;21(Suppl A):21A–24A
Percutaneous coronary interventions (PCI) are an integral part of the treatment of coronary artery disease and are the most commonly performed invasive therapeutic cardiac procedures. For over two decades, the dominant site of access has been the femoral artery and remains so today.¹ Despite many advantages, including a marked reduction in bleeding complications, there has been slow adoption of the transradial approach for coronary interventions since its introduction by Campeau in 1989.1,2 Currently, transradial access accounts for only 1–3% of all coronary interventions in the United States.³ With improvements in procedural technique and anticoagulation strategies, there has been a significant reduction in ischemic complications and adverse cardiac events associated with PCI.⁴ As a result, a growing emphasis has been placed on understanding the impact of bleeding complications on clinical outcomes and implementing ways to reduce them. Peri-procedural bleeding, including minor bleeding, is associated with worse outcomes such as myocardial infarction, stroke, stent thrombosis, and death.^5–8 In fact, a stepwise relationship between bleeding severity and short- and intermediate-term outcomes has been demonstrated.⁹ Vascular access-site complications are a major contributor to bleeding events. In a registry experience including 10,974 patients undergoing PCI, Kinnaird et al reported on the adverse outcomes associated with peri-procedural bleeding and found that the majority of bleeding events in their cohort were related to vascular access hematomas.¹⁰ Therefore, employing techniques that reduce access site bleeding complications, such as the transradial approach, can significantly reduce bleeding events and potentially improve both short- and long-term clinical outcomes. This review will discuss the data on the role of transradial PCI in reducing hemorrhagic complications as well as some of the challenges to adopting this technique and its impact on procedural outcomes. Bleeding Incidence and Outcomes Multiple studies have demonstrated that bleeding events associated with PCI are independent predictors of major adverse cardiac events and death.^5,6,8–12 A 30-day analysis of the impact of major bleeding on mortality and clinical outcomes from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial showed that those with major bleeding had a higher 30-day mortality (7.3% versus 1.2%, p p p p 10 Of the 588 major bleeding events, 400 of them were hematomas or retroperitoneal bleeds. This represents 68% of major bleeds that are due to vascular access. Of the 1,394 minor bleeds, 834 (60%) of them were hematomas or retroperitoneal bleeds. Rao and colleagues analyzed data from four multicenter trials of patients with ACS that included 26,452 patients and reported an association between increasing bleeding severity and a stepwise increase in 30-day and 6-month mortality.9 Not only was there was an incremental increase in both 30-day and 6-month mortality with increasing bleeding severity, but procedure-related moderate and severe bleeding was associated with higher mortality rates at 30 days and 6 months compared with non-procedure-related moderate or severe bleeds (Table 1). Data from the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry evaluated the relationship between access-site hematomas requiring blood transfusions and in-hospital and 1-year mortality.⁶ This included data on 6,656 patients and captured 120 hematomas requiring transfusion, with an incidence of 1.8%. Ninety-seven percent of the patients with hematomas had femoral artery access. Those with hematomas requiring transfusion were more likely to be older, female, have a lower BMI, and have more co-morbidities like renal, cerebrovascular, and pulmonary diseases. In-hospital mortality was approximately nine times higher in those with hematomas requiring transfusion than patients without (9.9% versus 1.2%). Similarly, at 1 year, mortality among those who developed a hematoma requiring transfusion was approximately 4.5 times higher than those who had not (18.8% versus 9.9%). After adjustment for demographic, clinical, angiographic, and procedural variables, hematomas requiring transfusion remained an independent predictor of death both within the hospital (OR = 3.59, 95% CI 1.66–7.77) and at 1 year (HR = 1.65, 95% CI 1.01–2.70). By combining patient data from the OASIS Registry,^13-15 OASIS-2 trial,¹⁶ and CURE trial,¹⁷ Eikelboom and colleagues evaluated the impact of bleeding on prognosis in 34,146 patients with acute coronary syndrome.¹⁸ At 6 months, 667 (2.0%) patients developed major bleeding. Those with major bleeding were five times more likely to die within the first 30 days (12.8% versus 2.5%, p p = 0.002). As in other studies, they reported a similar association between major bleeding and ischemic events such as myocardial infarction and stroke. Retroperitoneal hematomas, as a consequence of femoral artery access for PCI, have been shown to portend significant adverse events and are associated with a high mortality rate. Ellis and colleagues reported on data prospectively collected on 28,378 patients undergoing PCI.¹⁹ While the incidence of retroperitoneal hemorrhage was low in this cohort (176 patients/0.57%), subsequent outcomes in patients with retroperitoneal bleeding were substantially poor. Of those with retroperitoneal hematomas, 73.5% required blood transfusions and 10.4% of these patients died during hospitalization. In addition to clinical and demographic predictors of retroperitoneal bleeding, femoral artery sheath placement superior to the inferior epigastric artery (p 19 This highlights the importance of appropriate technique when gaining arterial access through the femoral approach to help avoid one of its most ominous complications. Arteriotomies located within the common femoral artery above the bifurcation but below the inferior epigastric artery reduce access-site complications, including retroperitoneal bleeding, compared with arteriotomies that are higher or lower.²⁰ The use of fluoroscopy to identify the femoral head can help maximize the likelihood of access into the common femoral artery by placing the skin incision 1–2 cm inferior to the middle part of the femoral head.²¹ It is unclear how common the use of routine fluoroscopy is to guide femoral arteriotomy in clinical practice. Despite its potential beneficial effect on appropriate arteriotomy location, patient variability in vascular anatomy likely does not guarantee appropriate location even when fluoroscopy is used. Transradial Approach Avoiding the femoral artery in favor of the radial artery for coronary angiography and interventions has been repeatedly shown to reduce bleeding complications. The radial artery is smaller in diameter, easily compressible, is remote from the retroperitoneal space, and does not have any adjacent major vascular structures. Early studies reported on the feasibility of this approach and began to demonstrate reductions in complications and cost.^22–24 Transradial PCI was subsequently shown to be safe and effective in the high-risk setting such as acute myocardial infarction, rescue PCI, and in conjunction with glycoprotein IIb/IIIa inhibitors.^25–28 More contemporary studies, as in the Prospective Registry of Vascular Access in Interventions in Lazio region (PREVAIL) have reported on the access-site specific outcomes in “real world” clinical settings.²⁹ They evaluated 1,052 patients having any percutaneous cardiovascular procedure requiring arterial access. In that cohort, 509 had radial access with 543 having femoral access. Approximately 40% of patients in both groups had coronary angioplasty. Analysis was performed on an intention-to-access basis. The primary endpoint was a combined incidence of in-hospital major and minor bleeding, stroke, and access-site vascular complications. They reported that radial access was significantly associated with a reduction in the primary outcome as compared to femoral access (4.2% versus 1.96%, p = 0.03). A combined secondary endpoint of in-hospital death and myocardial infarction or reinfarction was also lower in the radial access group (3.1% versus 0.6%, p = 0.005). Multivariate analysis adjusting for confounders showed that intention-to-access from the radial approach was independently associated with a reduction in both the primary endpoint (OR = 0.37, 95% CI 0.16–0.84) and secondary endpoint (OR = 0.14, 95% CI 0.03–0.62). Chase and colleagues reported on reductions in mortality, likely mediated through reduced transfusions, after percutaneous coronary interventions performed via the radial artery when compared with the femoral approach.³⁰ The Mortality benefit Of Reduced Transfusion after percutaneous coronary interventions via the Arm or Leg (MORTAL) study evaluated 38,872 PCI procedures in 32,822 patients in British Columbia. In this group, femoral access was used in 79.5% of the procedures, and radial access was used in 20.5%. In the femoral group, 2.8% of the procedures were complicated by the need for peri-procedural transfusions, while in the radial group, only 1.4% of the procedures were associated with a transfusion. The transfusion rate in the radial group was essentially half that found in the femoral group with an adjusted odds ratio of 0.59 (95% CI 0.48–0.73). This reduction in the need for transfusions was associated with a significant reduction in mortality at 30 days and 1 year (Table 2). The death rates at 30 days for the transfused group versus the non-transfused group were 12.6% and 1.3%, respectively. At 1 year, the death rates were 22.9% and 3.2%. The adjusted odds ratio for death at 30 days in the transfused group versus the non-transfused group was 4.01 (95% CI 3.08–5.22) and at 1 year was 3.58 (95% CI 2.94–4.36). The number of transfusions that must be avoided to prevent one death (number needed to treat) calculated to be approximately 15 transfusions. The data were then analyzed to compare mortality at 30 days and 1 year in the radial access group against the femoral access group. The adjusted odds ratio for 30-day mortality for transradial access versus femoral access was 0.71 (95% CI 0.61–0.82). At 1 year, the adjusted odds ratio for mortality was 0.83 (95% CI 0.71–0.98). When this comparison was made amongst the non-transfused patients, no significant difference in mortality was noted between the radial access and femoral access group, suggesting that the reductions in mortality observed with transradial access over femoral access are mediated through a decrease in bleeding and specifically in the need for transfusions. A meta-analysis comparing radial versus femoral approach for PCI performed by Agostoni and colleagues identified 12 studies that meet their criteria for inclusion.³¹ The primary outcomes evaluated were major adverse cardiac events (MACE), access site complications including bleeding, and procedural success. Major adverse cardiac events in the transradial and transfemoral groups were not significantly different at 2.1% and 2.4%, respectively. However, there were significantly fewer access-site complications in the transradial group (0.3%), compared to the femoral group (2.8%) with an odds ratio of 0.20 (95% CI 0.09–0.42, p p 3 In this large cohort, only 15 of the 7,804 (0.19%) patients who had radial access experienced vascular complications, defined as access site occlusion, peripheral embolization, arterial dissection, pseudoaneurysm, or ateriovenous fistula formation. Compared to the femoral approach, radial access had a significantly lower risk of bleeding (OR = 0.42, 95% CI 0.31–0.56) without any reduction in procedural success (adjusted OR = 1.02, 95% CI 0.93–1.12). Despite these advantages, this study found that the use of the radial approach for PCI in this large U.S. cohort remains very uncommon, with only 1.32% of the total procedures being a radial access PCI. Conclusions Periprocedural bleeding remains a significant complication after PCI. Multiple studies have shown that the most common site of bleeding in patients undergoing PCI is related to the vascular access site and that bleeding is associated with worse short- and long-term outcomes. The transradial approach to PCI has been repeatedly shown to reduce bleeding and improve clinical outcomes and mortality. Despite this, the transition to this approach, especially within the United States, remains slow with a very low percentage of PCIs being performed via the radial artery. This is likely related to lack of exposure to transradial PCI during fellowship training and operator discomfort with transradial techniques. If these hurdles can be overcome and the use of the transradial approach increases, the available data suggest that outcomes after PCI can be significantly improved. References 1. Jolly SS, Amlani S, Hamon M, Yusuf S, Mehta SR. Radial versus femoral access for coronary angiography or intervention and the impact on major bleeding and ischemic events: a systematic review and meta-analysis of randomized trials. Am Heart J 2009;157(1):132–140. 2. Campeau L. Percutaneous radial artery approach for coronary angiography. Cathet Cardiovasc Diagn 1989;16(1):3–7. 3. Rao SV, Ou FS, Wang TY, et al. Trends in the prevalence and outcomes of radial and femoral approaches to percutaneous coronary intervention: A report from the national cardiovascular data registry. JACC Cardiovasc Interv 2008;1:379–386. 4. Singh M, Rihal CS, Gersh BJ, et al. Twenty-five-year trends in in-hospital and long-term outcome after percutaneous coronary intervention. a single-institution experience. Circulation 2007;115:2835–2841. 5. Fuchs S, Kornowski R, Teplitsky I, et al. Major bleeding complicating contemporary primary percutaneous coronary interventions-incidence, predictors, and prognostic implications. Cardiovasc Revasc Med 2009;10:88–93. 6. Yatskar L, Selzer F, Feit F, et al. Access site hematoma requiring blood transfusion predicts mortality in patients undergoing percutaneous coronary intervention: Data from the National Heart, Lung, and Blood Institute Dynamic Registry. Catheter Cardiovasc Interv 2007;69:961–966. 7. Feit F, Voeltz MD, Attubato MJ, et al. Predictors and impact of major hemorrhage on mortality following percutaneous coronary intervention from the REPLACE-2 Trial. Am J Cardiol 2007;100:1364–1369. 8. Manoukian, SV, F Feit, R Mehran et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes. an analysis from the ACUITY Trial. J Am Coll Cardiol 2007;49:1362–1368. 9. Rao SV, O'Grady K, Pieper KS, et al. Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes. Am J Cardiol 2005;96:1200–1206. 10. Kinnaird TD, Stabile E, Mintz GS, et al. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions. Am J Cardiol 2003;92:930–935. 11. Lincoff AM, Bittl JA, Harrington RA, et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention. REPLACE-2 randomized trial. JAMA 2003;289:853–863. 12. Bertrand OF, Larose E, Rodes-Cabau J, et al. Incidence, predictors, and clinical impact of bleeding after transradial coronary stenting and maximal antiplatelet therapy. Am Heart J 2009;157:164–169. 13. Yusuf S, Flather M, Pogue J, et al. Variations between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina or myocardial infarction without initial ST elevation. OASIS (Organisation to Assess Strategies for Ischaemic Syndromes) Registry Investigators. Lancet 1998;352:507–514. 14. Chinese Coordinating Center of OASIS Registry. The clinical characteristics of acute coronary syndrome in China. Zhonghua Nei Ke Za Zhi 2003;42:697–700. 15. Prabhakaran D, Yusuf S, Mehta S, et al. Two-year outcomes in patients admitted with non-ST elevation acute coronary syndrome. results of the OASIS registry 1 and 2. Indian Heart J 2005;57:217–225. 16. [No authors listed]. Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischaemia without ST elevation: a randomised trial. Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators. Lancet 1999;353:429–438. 17. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. New Engl J Med 2001;345:494–502. 18. Eikelboom JW, Mehta SR, Anand SS, et al. Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 2006;114:774–782. 19. Ellis SG, Bhatt D, Kapadia S, et al. Correlates and outcomes of retroperitoneal hemorrhage complicating percutaneous coronary intervention. Catheter Cardiovasc Interv 2006;67:541–545. 20. Sherev DA, Shaw RE, Brent BN. Angiographic predictors of femoral access site complications. implication for planned percutaneous coronary intervention. Catheter Cardiovasc Interv 2005;65:196–202. 21. Garrett PD, Eckart RE, Bauch TD, et al. Fluoroscopic localization of the femoral head as a landmark for common femoral artery cannulation. Catheter Cardiovasc Interv 2005;65:205–207. 22. Mann JT 3rd, Cubeddu MG, Schneider JE, Arrowood M. Right radial access for PTCA. A Prospective Study Demonstrates Reduced Complications and Hospital Charges. J Invasive Cardiol 1996;8(Suppl D):40D–44D. 23. 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;29:1269–1275. 24. Benit E, Missault L, Eeman T, et al. Brachial, radial, or femoral approach for elective Palmaz-Schatz stent implantation. a randomized comparison. Cathet Cardiovasc Diagn 1997;41:124–130. 25. 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. 26. Cantor WJ, Puley G, Natarajan MK, et al. 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. Am Heart J 2005;150:543–549. 27. Brasselet C, Tassan S, Nazeyrollas P, et al. Randomised comparison of femoral versus radial approach for percutaneous coronary intervention using abciximab in acute myocardial infarction: results of the FARMI trial. Heart 2007;93:1556–1561. 28. Valsecchi O, Musumeci G, Vassileva A, et al. Safety, feasibility and efficacy of transradial primary angioplasty in patients with acute myocardial infarction. Ital Heart 2003;4:329–334. 29. Pristipino C, Trani C, Nazzaro MS, et al. Major improvement of percutaneous cardiovascular procedure outcomes with radial artery catheterization: results from the PREVAIL study. Heart 2009;95:476–482. 30. Chase AJ, Fretz EB, Warburton WP, et al. Association of the arterial access site at angioplasty with transfusion and mortality. the M.O.R.T.A.L study (Mortality benefit Of Reduced Transfusion after percutaneous coronary intervention via the Arm or Leg). Heart 2008;94:1019–1025. 31. Agostoni P, Biondi-Zoccai GG, de Benedictis ML, et al. Radial versus femoral approach for percutaneous coronary diagnostic and interventional procedures; Systematic overview and meta-analysis of randomized trials. J Am Coll Cardiol 2004;44:349–356.