Curr Treat Options Cardio Med (2014) 16:305 DOI 10.1007/s11936-014-0305-6
Coronary Artery Disease (D Feldman, Section Editor)
Bleeding Complications After PCI and the Role of Transradial Access Amit N. Vora, MD, MPH* Sunil V. Rao, MD Address *Duke Clinical Research Institute, 2400 Pratt Street, Durham, NC 27705, USA Email: [email protected]
Published online: 12 April 2014 * Springer Science+Business Media New York 2014
This article is part of the Topical Collection on Coronary Artery Disease Keywords Transradial access
I
Cardiac catheterization
I
Bleeding after PCI
I
Transradial complications
Opinion statement Bleeding events are the most common complications following percutaneous coronary intervention (PCI) and are associated with increases in short- and long-term mortality, nonfatal myocardial infarction, stroke, hospital length of stay, and hospital cost. Over time, there has been a decrease in periprocedural bleeding, primarily due to improvements in antithrombotic therapy; however, transradial (TR) catheterization has been shown to be an important strategy to minimize access site bleeding and potentially improve outcomes among patients with ST-segment elevation myocardial infarction. The rate of TR catheterization has been increasing significantly over the past few years and now accounts for an increasing proportion of procedures performed in the United States. Results from the recently published RIVAL Trial have shown comparable efficacy between transradial and transfemoral (TF) approaches with significant reduction in vascular access complications in the TR group. TR access in the STEMI population was prospectively assessed in the RIFLE-STEACS Trial and demonstrated significant reduction in the primary outcome of composite death/MI/stroke/target vessel revascularization/non-CABG bleeding. More recent studies have also demonstrated cost savings with TR access, related primarily to decreased hospital length of stay. While previous studies have shown increased operator radiation exposure compared to a TF approach, the most recent data suggest no significant difference in radiation at higher volume centers.
Introduction Over the last few decades, improvements in the efficacy of percutaneous coronary intervention (PCI) have
progressed to the point that the strategy now serves as the cornerstone in the treatment of ischemic heart
305, Page 2 of 11
Curr Treat Options Cardio Med (2014) 16:305
disease and acute coronary syndromes (ACS). According to most recent data, close to one million cardiac catheterizations and 500,000 PCIs are performed annually in the United States [1]. Key improvements in PCI technology over that period have included device miniaturization, the evolution of guidewire and stent technology, and advances in pharmacotherapeutics with antiplatelet and antithrombotic agents. These advances have led to improved outcomes in PCI efficacy and durability. Although rates of major or clinically significant bleeding have decreased markedly over the past two decades, they still occur in about 5 % of patients and have significant deleterious short- and long-term consequences. A significant proportion of this bleeding is due to vascular access site bleeding, with higher proportions seen in patients undergoing PCI for stable
angina or STEMI compared with those with NSTEMI [2] Traditionally, cardiac catheterization and PCI have been performed via the transfemoral (TF) route. Although the transradial (TR) approach was described more than two decades ago, until recently it has seen slow rates of adoption among operators in the United States. Contemporary large clinical trials have compared the TR approach to the traditional TF approach and have demonstrated similar, if not better, efficacy with superior safety. The purpose of this review is to describe the incidence and importance of bleeding complications in PCI, evaluate the most recent clinical data demonstrating the efficacy and safety of TR access in PCI, discuss other non-clinical concerns regarding TR access such as radiation exposure and cost, and describe the evaluation and management of the most important complications of TR access.
PCI and bleeding rates Bleeding events are among the most common complications of PCI; estimates vary in the literature but incidence of major bleeding events have ranged from 2.2 to 14 % [3–6] depending on the population studied and the definition used, with more recent studies suggesting that the incidence of clinically significant bleeding in today’s era is closer to 5 %. In a recent analysis of the NCDR CathPCI cohort, Chhatriwalla et al. used the registry’s definition of bleeding (with events identified by sites) and found a rate of 1.7 % of major bleeding events with a riskadjusted hazard ratio for in-hospital mortality after a bleeding complication to be 2.92 (95 % CI 3.78 – 3.06); the population attributable risk for mortality from major bleeding alone was 12.1 % in the entire cohort, similar to prior studies [7]. Other studies have also shown that postprocedure bleeding events are associated with increases in short- and long-term mortality, nonfatal myocardial infarction, stroke, hospital length of stay, and hospital cost [3–11]. Despite the recent decline in clinically significant major bleeding events, the likelihood of short- and long-term consequences has remained proportional to the frequency of events [12]. Bleeding events can be generally classified into access site bleeding and non-access site bleeding. Access site bleeding for TF patients can range from a small, self-limited hematoma to a large, hemodynamically significant retroperitoneal hematoma. In a retrospective cohort analysis by Kinnaird et al. of 10,974 patients undergoing PCI [4], the incidence of Thrombolysis In Myocardial Infarction (TIMI) major bleeding was 5.4 % (n=588) and TIMI minor bleeding was 12.7 % (n=1,394), with access-site bleeding comprising 79.3 % and 59.8 % of bleeding cases,
Curr Treat Options Cardio Med (2014) 16:305
Page 3 of 11, 305
respectively. Patients with major bleeding in this study had increased rates of in-hospital and annual mortality. Predictors of increased systemic bleeding complications have included age, ACS presentation, increased anticoagulation, longer times to sheath removal, and comorbidities such as renal disease and congestive heart failure [13–16]. The proportion of major bleeding events attributable to the vascular access site depends on the patient’s clinical presentation, with STEMI patients having a larger proportion of access-site bleeding compared with NSTEMI patients [2]. PCI performed for stable angina has been associated with the lowest overall bleeding rates. However, the proportion of access site bleeding events follows a different distribution, with higher rates of bleeding in the stable angina and STEMI populations compared to the NSTE-ACS population [2]. Rates of major bleeding have decreased significantly over the last few decades as the focus for PCI has shifted from efficacy to a more comprehensive emphasis on efficacy and safety. Part of this reduction in bleeding has been associated with improved miniaturization of devices, permitting most PCI procedures to be performed with 5- or 6-French sheaths as opposed to sheaths sized 9-French or greater. Most of the reduction, however, has been due to changes in periprocedural drug therapies, especially bivalirudin [17], and less to the use of either TR access or vascular closure devices (VCDs) [18]. The data for VCDs has been mixed; randomized trial data have not shown significant benefit when compared to manual compression, though observational data seem to suggest some benefit. One meta-analysis showed slight benefit with VCDs (pooled OR 0.89, 95 % CI 0.86 – 0.91) [19], whereas another meta-analysis of 30 studies involving 37,066 patients showed similar complication rates between VCDs and mechanical compression [20]. A more recent analysis of NCDR data by Marso et al. studied the effects of various bleeding avoidance strategies and found decreased rates of bleeding in patients with vascular closure devices, bivalirudin, or both when compared to patients undergoing manual compression [21].
Transradial procedures and clinical outcomes The radial approach for coronary angiography was first described in 1989 in a series of 100 patients by Campeau [22] and subsequently by Otaki [23] in 1992. It started to gain in popularity after it was described by Kiemeneij and Laarman [24, 25] in 1994 and by Lotan et al. in 1995 [26]. Historically, TR access has seen low rates of implementation within the US, though adoption of TR access has been increasing. Data from 2,820,874 patients in the NCDR CathPCI registry show that TR adoption rates have increased 16-fold over 5 years, from 1.2 % in 2007 to 16.1 % in 2012 and accounted for 6.3 % of total procedures during that time [27]. Compared with TF access, TR access was associated with a significantly lower rate of bleeding (OR 0.5, 95 % CI 0.49 – 0.54) and access site complications (OR 0.39, 95 % CI 0.31 – 0.50), differences that tracked across all significant age, sex, and comorbidity subgroups.
305, Page 4 of 11
Curr Treat Options Cardio Med (2014) 16:305 The RIVAL (Radial Versus Femoral Access for Coronary Intervention) trial [28••] was the first large-scale, multicenter international clinical trial that randomized 7,021 patients presenting with acute coronary syndrome (ACS) undergoing cardiac catheterization to either femoral (n=3,514) or radial (n=3,507) access. Approximately two-thirds of the patients underwent PCI; the definition of major bleeding used in the study was consistent with the definition used in the CURRENT-OASIS 7 trial – major bleeding was defined as bleeding that was 1) fatal, 2) required transfusion of two or more units of packed red cells, 3) caused hypotension requiring inotrope therapy, 4) needed surgical intervention, 5) caused severely disabling sequelae, 6) was intracranial or intraocular, or 7) led to a hemoglobin drop of 5 g/dL [28••]. Trial results are shown in (Fig. 1; Table 1) and revealed no advantage of radial access over femoral access but significantly lower major vascular access complications at 30 days. In addition, when bleeding was defined using a more access sitesensitive definition like the ACUITY trial definition, there was a significant reduction with radial approach. Importantly, non-access site bleeding accounted for two-thirds of overall bleeding events in the RIVAL trial, which explains, in part, the overall neutral result since radial access would only affect access-site bleeding and not non-access-site bleeding. A pre-specified post-hoc analysis of the RIVAL trial by Mehta et al. [29] assessed efficacy and bleeding outcomes among patients presenting with STEMI and found that radial access was associated with a significant reduction in 30-day mortality (Table 2). Interestingly, this occurred despite similar rates of bleeding in both the radial and femoral access groups. Because of these mixed results and the fact that the overall trial was neutral, the RIVAL trial suggests, but does not appear to prove, that radial access may have significant outcome benefits among patients with STEMI undergoing PCI (Table 2). To address this, radial access in patients undergoing primary PCI for STEMI was prospectively assessed in the RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) trial [30••], which randomized 1,001 patients presenting with STEMI to TR (n=500) or TF (501) access. The primary outcome of composite death/MI/stroke/target vessel revascularization/non-CABG bleeding occurred in 13.6 % of TR patients versus 21.0 % of TF patients (p=0.003) with decreased mortality (5.2 % vs. 9.2 %, p=0.02) and bleeding (7.8 % vs. 12.2 %, p=0.026) in the TR arm. This rate of bleeding reduction is similar to what was seen in the HORIZONS-AMI trial comparing bivalirudin to a combination of unfractionated heparin/ glycoprotein IIb/IIIa therapy [31]. There are no US-based randomized data on transradial primary PCI. There are, however, observational data. Baklanov et al. note from the NCDR CathPCI Registry that TR access in STEMI cases has increased markedly from 0.9 % of all cases to 6.4 % of all cases [32]. Although they note a modest increase in door-to-first device times (78 min vs. 74 min, pG0.001), TR access was associated with decreased bleeding (OR 0.62, 95 % CI 0.53 – 0.72, pG0.001) and lower risk of adjusted inhospital mortality (OR 0.76, 95 % CI 0.59 – 0.99, p=0.0455).
Curr Treat Options Cardio Med (2014) 16:305
Page 5 of 11, 305
Figure 1. The primary results from the RIVAL Trial show comparable rates for the primary outcome of death, myocardial infarction, stroke, or non-CABG related major bleeding (a) and non-CABG bleeding (b).
Transradial procedures and costs From a cost perspective, the clinical benefits of TR access, which have included lower access site complications, lower bleeding, and earlier ambulation and length of stay, have to be balanced against an initially steep operator learning curve, increased procedural times [33], and increased rates of crossover to femoral access [33].
305, Page 6 of 11
Curr Treat Options Cardio Med (2014) 16:305
Table 1. Primary results from the RIVAL trial Primary outcome Death/MI/ stroke/non-CABG bleeding at 30 days Secondary outcomes Death, MI, or stroke Non-CABG major bleeding Death MI Stroke Major vascular complications
Radial (n=3507)
Femoral (n=3514)
128 (3.7 %)
139 (4.0 %)
0.92 (0.72–1.17)
112 24 44 60 20 49
114 33 51 65 14 131
0.98 0.73 0.86 0.92 1.43 0.37
(3.2 (0.7 (1.3 (1.7 (0.6 (1.4
%) %) %) %) %) %)
(3.2 (0.9 (1.5 (1.9 (0.4 (3.7
%) %) %) %) %) %)
Hazard Ratio (9 5 % CI)
(0.76–1.28) (0.43–1.23) (0.58–1.29) (0.65–1.31) (0.72–2.83) (0.27–0.52)
p-value 0.50
0.90 0.23 0.47 0.65 0.30 G0.0001
Applegate et al. evaluated the effects and cost-effectiveness of transitioning a cardiac catheterization laboratory from a “femoral first” approach to a “radial first” approach in a propensity-matched patient cohort, finding marginally higher cost for diagnostic catheterization but a $732 cost savings for TR PCI, mostly attributed to a decrease in access site complications [34]. A retrospective cohort analysis using data from the Premier research database performed propensity matching on 609 (0.1 % of the study population) TR PCI cases with 60,900 TF PCI cases and examined cost differences between the study groups, finding lower adjusted total costs by $553 in the TR PCI group, driven primarily by a 0.3 day reduction in length of stay and bleeding complications [35]. This difference was more pronounced in patients at higher risks of bleeding. A cost-benefit analysis from a meta-analysis of 14 previous studies of TR access showed that TR cases cost $275 less than TF cases from a hospital perspective [33]. Amin et al. performed a detailed cost analysis using a retrospective cohort of 7,121 procedures at five US hospitals, of which 1,219 (17 %) were TR [36•]. TR patients had a lower length of stay and decreased bleeding events and were associated with a cost savings of $830 per patient, with a graded increase of savings to $1,630 in patients with highest risk of bleeding. Procedural costs were similar between the two approaches, implying most of the cost savings was attributed to decreased length of stay. Given the current bundled payment reimbursement structure adopted by the Centers for Medicare and Medicaid Services (CMS), there may be a significant value proposition with increased adoption of TR access, providing a safer therapy (with decreased bleeding) with decreased cost, driven primarily from shorter hospital length of stay[37].
Volume-outcome relationship in TR PCI There has been a long-described relationship between the inverse relationship of volume of a particular procedure and its associated outcomes [38]. This is particularly apt in the setting of transradial PCI. It should be
(0.83–1.48) 0.491 0.025 (0.91–1.71) 0.176 0.011 (0.35–1.23) 0.190 0.557 (0.29–0.58) G0.001 0.624 (0.94–2.92) 0.082 0.001 (0.69–1.53) 0.903 0.269 (0.67–3.30) 0.335 0.864 (0.26–0.55) G0.001 0.885 1.11 1.25 0.66 0.41 1.66 1.03 1.48 0.38 (3.46) (2.71) (0.96) (4.46) (0.76) (1.87) (0.40) (3.82) 87 68 24 112 19 47 10 96 (3.84) (3.37) (0.63) (1.84) (1.25) (1.92) (0.59) (1.45) 98 86 16 47 32 49 15 37 0.026 0.031 0.870 0.009 0.006 0.225 0.696 0.002 (0.38–0.94) (0.36–0.95) (0.36–2.39) (0.28–0.84) (0.20–0.76) (0.30–1.33) (0.35–4.84) (0.19–0.70) 0.60 0.59 0.92 0.49 0.39 0.63 1.30 0.36 52 (5.19) 46 (4.59) 9 (0.91) 41 (4.10) 32 (3.19) 18 (1.82) 4 (0.40) 35 (3.49) (3.14) (2.72) (0.84) (1.99) (1.26) (1.16) (0.53) (1.26) 30 26 8 19 12 11 5 12 Primary outcome Death, MI or stroke Non-CABG major bleed ACUITY major bleed Death MI Stroke Major vascular access site complication
NSTE-ACS p Value Radial Femoral HR (n=2,552) (n=2,511) (95 % CI) STEMI Radial Femoral HR (n=955) (n=1,003) (95 % CI)
Table 2. Subgroup analysis from the RIVAL Trial of patients with STEMI
p Value p-interaction
Curr Treat Options Cardio Med (2014) 16:305
Page 7 of 11, 305 noted that the procedural success in the large clinical trials has been in the setting of experienced operators in high-volume TR centers. Operators in the RIVAL trial, for example, performed a median 300 PCIs per year (IQR 190 – 400) with 40 % (IQR 25 – 70 %) performed via the TR route [28••]. Subgroup analysis showed significant interaction between the primary composite outcome and radial PCI volume by center (HR 0.49, 95 % CI 0.28 – 0.87, p-interaction=0.021). Further analyses of outcomes stratified by PCI center volume showed a reduction in death/MI/stroke (HR 0.50, 95 % CI 0.27 – 0.92, p=0.027, p-interaction=0.013) and major vascular complications (HR 0.18, 95 % CI 0.08 – 0.37, pG0.00, p-interaction=0.019). This volume-outcome relationship also extends to safety parameters related to the radial approach – namely, the potentially increased radiation exposure compared with the femoral approach. Studies have consistently shown that the radial approach is associated with longer fluoroscopy times and radiation exposure; however, more detailed analyses suggest that these differences are dependent on operator and center proficiency. A substudy of the RIVAL trial assessed radiation differences between patients undergoing TR versus TF access [39•]. Although fluoroscopy time was noted to be higher in the TR arm (9.3 vs. 8.0 min, p G0.001), there was only a small difference in median air kerma (1,046 vs. 930 mGy, p=0.051) and no difference in median dose area product (DAP) (52.8 Gy-cm2 vs 51.2 Gy-cm2, p=0.83). However, when stratified according to center procedural volume, there was a marked increase in air kerma among the lowest volume centers, with no significant differences between radial and femoral access among high volume radial sites or operators. Similarly, Lo et al. prospectively studied the effects of operator experience and radiation exposure by measuring differences in radiation exposure by TR or TF access routes among a total of 100 cases performed by experts (91,000 procedures and 90 % of cases performed at the particular access site) versus intermediate trainee cardiologists (500 – 1,000 procedures and equal frequencies among the different access sites) [40]. Among the expert interventionalists they found an increase in procedure time with TR access but no differences in operator or patient radiation exposure. Among the trainee cardiologists, although there was no difference in procedure time or operator or patient radi-
305, Page 8 of 11
Curr Treat Options Cardio Med (2014) 16:305 ation exposure between access sites, there was a 25 % increase in operator exposure and a 10 – 15 % increase in patient exposure. These data demonstrate that that when controlling for operator and center radial proficiency, there is likely no increase in radiation exposure for neither patient nor operator, although there is a learning curve needed to achieve expertise in TR PCI.
Transradial learning curve The number of cases needed to achieve proficiency defines the so-called learning curve. Studies have described a learning curve with respect to TR PCI, showing an improvement in rates of procedural success, fluoroscopy times, and contrast utilization with increasing operator volume [41, 42]. However, this learning curve may not be as steep as previously thought. Ball et al. analyzed single center data consisting of 1,672 single vessel PCIs and stratified by operator volume [41]. They note a steep learning curve with no significant further reduction in TR failure rate after only 50 cases with only small changes in other procedural outcomes such as fluoroscopy time, contrast use, and vascular complications. Rao and Krucoff [43] have advocated the development of a “radial first” program in order to develop comfort and competency with regard to TR procedures not only by the operator but also by the nursing and support staff. Then, once there is comfort and expertise with TR access in the lowerrisk population, there should be in improved effort and commitment to consider the use of TR PCI on all eligible patients regardless of acuity. It should be noted that a “radial first” program is not a “radial only” program and there are important patient characteristics and clinical situations that would dictate use of a TF approach.
Conclusion Major, clinically significant bleeding is a common though largely avoidable complication of PCI. Nevertheless, it is still responsible for significant short- and long-term morbidity and mortality. The use of TR access in the United States, though initially low, has increased markedly over the previous 5 years and will likely continue to do so as operators become more experienced with the procedure. Large randomized data have shown similar outcomes to TF PCI but with lower vascular access complications. More recent trial data suggests mortality benefit in the STEMI population in addition to reduced bleeding and vascular complications. Although previously associated with high rates of procedural failure and increased radiation to the patient and the operator, more recent observational and trial data have failed to show significant difference, especially as operators become more proficient. Emerging data also show reduced cost with TR PCI, mostly related to decreased hospital length-of-stay and reduced bleeding complications. The benefits of TR access will likely increase operator adoption and proficiency increases so the technique can be used safely and effectively on the patient popula-
Curr Treat Options Cardio Med (2014) 16:305
Page 9 of 11, 305
tion at highest risk for bleeding complication, thus attenuating the “risktreatment paradox.”
Compliance with Ethics Guidelines Conflict of Interest Dr. Amit N. Vora declares no potential conflicts of interest relevant to this article. Dr. Sunil V. Rao reports consulting (modest) from The Medicines Company. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
2.
3.
4.
5.
6.
7.
8.
Go AS et al. Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6–e245. Rao SV et al. The transradial approach to percutaneous coronary intervention: historical perspective, current concepts, and future directions. J Am Coll Cardiol. 2010;55(20):2187–95. Batchelor WB et al. Contemporary outcome trends in the elderly undergoing percutaneous coronary interventions: results in 7,472 octogenarians. National Cardiovascular Network Collaboration. J Am Coll Cardiol. 2000;36(3):723–30. Kinnaird TD et al. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions. Am J Cardiol. 2003;92(8):930–5. Lauer MA et al. Practice patterns and outcomes of percutaneous coronary interventions in the United States: 1995 to 1997. Am J Cardiol. 2002;89(8):924–9. Popma JJ et al. Vascular complications after balloon and new device angioplasty. Circulation. 1993;88(4 Pt 1):1569–78. Manoukian SV 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(12):1362–8. Pinto DS et al. Economic evaluation of bivalirudin with or without glycoprotein IIb/IIIa inhibition ver-
9.
10.
11.
12.
13.
14.
sus heparin with routine glycoprotein IIb/IIIa inhibition for early invasive management of acute coronary syndromes. J Am Coll Cardiol. 2008;52(22):1758–68. Aronow HD et al. Predictors of length of stay after coronary stenting. Am Heart J. 2001;142(5):799– 805. Cohen DJ et al. Economic evaluation of bivalirudin with provisional glycoprotein IIB/IIIA inhibition versus heparin with routine glycoprotein IIB/IIIA inhibition for percutaneous coronary intervention: results from the REPLACE-2 trial. J Am Coll Cardiol. 2004;44(9):1792–800. Lopes RD et al. Advanced age, antithrombotic strategy, and bleeding in non-ST-segment elevation acute coronary syndromes: results from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. J Am Coll Cardiol. 2009;53(12):1021–30. Nathan S, Rao SV. Radial versus femoral access for percutaneous coronary intervention: implications for vascular complications and bleeding. Curr Cardiol Rep. 2012;14(4):502–9. Doyle BJ et al. Major femoral bleeding complications after percutaneous coronary intervention: incidence, predictors, and impact on long-term survival among 17,901 patients treated at the Mayo Clinic from 1994 to 2005. JACC Cardiovasc Interv. 2008;1(2):202–9. Feit F et al. Predictors and impact of major hemorrhage on mortality following percutaneous coronary
305, Page 10 of 11 intervention from the REPLACE-2 Trial. Am J Cardiol. 2007;100(9):1364–9. 15. Kirtane AJ et al. Correlates of bleeding events among moderate- to high-risk patients undergoing percutaneous coronary intervention and treated with eptifibatide: observations from the PROTECT-TIMI30 trial. J Am Coll Cardiol. 2006;47(12):2374–9. 16. Mehta SK et al. Bleeding in patients undergoing percutaneous coronary intervention: the development of a clinical risk algorithm from the National Cardiovascular Data Registry. Circ Cardiovasc Interv. 2009;2(3):222–9. 17. Stone GW et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006;355(21):2203–16. 18. Subherwal S et al. Temporal trends in and factors associated with bleeding complications among patients undergoing percutaneous coronary intervention: a report from the National Cardiovascular Data CathPCI Registry. J Am Coll Cardiol. 2012;59(21):1861–9. 19. Vaitkus PT. A meta-analysis of percutaneous vascular closure devices after diagnostic catheterization and percutaneous coronary intervention. J Invasive Cardiol. 2004;16(5):243–6. 20. Nikolsky E et al. Vascular complications associated with arteriotomy closure devices in patients undergoing percutaneous coronary procedures: a meta-analysis. J Am Coll Cardiol. 2004;44(6):1200–9. 21. Marso SP et al. Association between use of bleeding avoidance strategies and risk of periprocedural bleeding among patients undergoing percutaneous coronary intervention. JAMA. 2010;303(21):2156–64. 22. Campeau L. Percutaneous radial artery approach for coronary angiography. Cathet Cardiovasc Diagn. 1989;16(1):3–7. 23. Otaki M. Percutaneous transradial approach for coronary angiography. Cardiology. 1992;81(6):330–3. 24. Kiemeneij F, Laarman GJ. Percutaneous transradial artery approach for coronary Palmaz-Schatz stent implantation. Am Heart J. 1994;128(1):167–74. 25. Kiemeneij F, Laarman GJ, de Melker E. Transradial artery coronary angioplasty. Am Heart J. 1995;129(1):1–7. 26. Lotan C et al. Transradial approach for coronary angiography and angioplasty. Am J Cardiol. 1995;76(3):164–7. 27. Feldman DN et al. Adoption of radial access and comparison of outcomes to femoral access in percutaneous coronary intervention: an updated report from the national cardiovascular data registry (20072012). Circulation. 2013;127(23):2295–306. 28.•• Jolly SS et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised,
Curr Treat Options Cardio Med (2014) 16:305 parallel group, multicentre trial. Lancet. 2011;377(9775):1409–20. The RIVAL Trial is the largest randomized trial comparing the transfemoral and transradial approaches to catheterization. 29. Mehta SR et al. Effects of radial versus femoral artery access in patients with acute coronary syndromes with or without ST-segment elevation. J Am Coll Cardiol. 2012;60(24):2490–9. 30.•• Romagnoli E et al. Radial versus femoral randomized investigation in ST-segment elevation acute coronary syndrome: the RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) study. J Am Coll Cardiol. 2012;60(24):2481–9. The RIFLE-STEACS is one of the largest trials specifically looking at the use of transradial access in patients presenting with ST-elevation myocardial infarction. 31. Stone GW et al. Bivalirudin during Primary PCI in Acute Myocardial Infarction. N Engl J Med. 2008;358(21):2218–30. 32. Baklanov DV et al. The prevalence and outcomes of transradial percutaneous coronary intervention for STsegment elevation myocardial infarction: analysis from the National Cardiovascular Data Registry (2007 to 2011). J Am Coll Cardiol. 2013;61(4):420–6. 33. Mitchell MD et al. Systematic review and cost-benefit analysis of radial artery access for coronary angiography and intervention. Circ Cardiovasc Qual Outcomes. 2012;5(4):454–62. 34. Applegate R, et al. Cost effectiveness of radial access for diagnostic cardiac catheterization and coronary intervention. Catheter Cardiovasc Interv. 2013;82(4):E375–84. 35. Safley DM et al. Comparison of costs between transradial and transfemoral percutaneous coronary intervention: a cohort analysis from the Premier research database. Am Heart J. 2013;165(3):303–9 e2. 36.• Amin AP, et al. Costs of Transradial Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2013;6(8):827–34. This is a retrospective study assessing cost differences between transradial and transfemoral access, describing the potential costs savings from transradial access, predominantly due to a shorter length of stay. 37. Rao SV, Patel MR. The Value Proposition in Percutaneous Coronary Intervention. J Am Coll Cardiol Intv. 2013;6(8):835–7. 38. McGrath PD et al. RElation between operator and hospital volume and outcomes following percutaneous coronary interventions in the era of the coronary stent. JAMA. 2000;284(24):3139–44. 39.• Jolly SS et al. Effect of radial versus femoral access on radiation dose and the importance of procedural volume: a substudy of the multicenter randomized RIVAL trial. JACC Cardiovasc Interv. 2013;6(3):258–66. This is a good study assessing the importance of operator volume on radiation exposure during TR catheterization.
Curr Treat Options Cardio Med (2014) 16:305 40.
41.
Lo TS et al. Impact of access site selection and operator expertise on radiation exposure; a controlled prospective study. Am Heart J. 2012;164(4):455–61. Ball WT et al. Characterization of operator learning curve for transradial coronary interventions. Circ Cardiovasc Interv. 2011;4(4):336–41.
Page 11 of 11, 305 42.
43.
Spaulding C et al. Left radial approach for coronary angiography: results of a prospective study. Cathet Cardiovasc Diagn. 1996;39(4):365–70. Rao SV, Krucoff MW. Radial first: paradox+proficiency=opportunity. J Am Heart Assoc. 2013;2(3):e000281.
Coronary Artery Disease (D Feldman, Section Editor)
Bleeding Complications After PCI and the Role of Transradial Access Amit N. Vora, MD, MPH* Sunil V. Rao, MD Address *Duke Clinical Research Institute, 2400 Pratt Street, Durham, NC 27705, USA Email: [email protected]
Published online: 12 April 2014 * Springer Science+Business Media New York 2014
This article is part of the Topical Collection on Coronary Artery Disease Keywords Transradial access
I
Cardiac catheterization
I
Bleeding after PCI
I
Transradial complications
Opinion statement Bleeding events are the most common complications following percutaneous coronary intervention (PCI) and are associated with increases in short- and long-term mortality, nonfatal myocardial infarction, stroke, hospital length of stay, and hospital cost. Over time, there has been a decrease in periprocedural bleeding, primarily due to improvements in antithrombotic therapy; however, transradial (TR) catheterization has been shown to be an important strategy to minimize access site bleeding and potentially improve outcomes among patients with ST-segment elevation myocardial infarction. The rate of TR catheterization has been increasing significantly over the past few years and now accounts for an increasing proportion of procedures performed in the United States. Results from the recently published RIVAL Trial have shown comparable efficacy between transradial and transfemoral (TF) approaches with significant reduction in vascular access complications in the TR group. TR access in the STEMI population was prospectively assessed in the RIFLE-STEACS Trial and demonstrated significant reduction in the primary outcome of composite death/MI/stroke/target vessel revascularization/non-CABG bleeding. More recent studies have also demonstrated cost savings with TR access, related primarily to decreased hospital length of stay. While previous studies have shown increased operator radiation exposure compared to a TF approach, the most recent data suggest no significant difference in radiation at higher volume centers.
Introduction Over the last few decades, improvements in the efficacy of percutaneous coronary intervention (PCI) have
progressed to the point that the strategy now serves as the cornerstone in the treatment of ischemic heart
305, Page 2 of 11
Curr Treat Options Cardio Med (2014) 16:305
disease and acute coronary syndromes (ACS). According to most recent data, close to one million cardiac catheterizations and 500,000 PCIs are performed annually in the United States [1]. Key improvements in PCI technology over that period have included device miniaturization, the evolution of guidewire and stent technology, and advances in pharmacotherapeutics with antiplatelet and antithrombotic agents. These advances have led to improved outcomes in PCI efficacy and durability. Although rates of major or clinically significant bleeding have decreased markedly over the past two decades, they still occur in about 5 % of patients and have significant deleterious short- and long-term consequences. A significant proportion of this bleeding is due to vascular access site bleeding, with higher proportions seen in patients undergoing PCI for stable
angina or STEMI compared with those with NSTEMI [2] Traditionally, cardiac catheterization and PCI have been performed via the transfemoral (TF) route. Although the transradial (TR) approach was described more than two decades ago, until recently it has seen slow rates of adoption among operators in the United States. Contemporary large clinical trials have compared the TR approach to the traditional TF approach and have demonstrated similar, if not better, efficacy with superior safety. The purpose of this review is to describe the incidence and importance of bleeding complications in PCI, evaluate the most recent clinical data demonstrating the efficacy and safety of TR access in PCI, discuss other non-clinical concerns regarding TR access such as radiation exposure and cost, and describe the evaluation and management of the most important complications of TR access.
PCI and bleeding rates Bleeding events are among the most common complications of PCI; estimates vary in the literature but incidence of major bleeding events have ranged from 2.2 to 14 % [3–6] depending on the population studied and the definition used, with more recent studies suggesting that the incidence of clinically significant bleeding in today’s era is closer to 5 %. In a recent analysis of the NCDR CathPCI cohort, Chhatriwalla et al. used the registry’s definition of bleeding (with events identified by sites) and found a rate of 1.7 % of major bleeding events with a riskadjusted hazard ratio for in-hospital mortality after a bleeding complication to be 2.92 (95 % CI 3.78 – 3.06); the population attributable risk for mortality from major bleeding alone was 12.1 % in the entire cohort, similar to prior studies [7]. Other studies have also shown that postprocedure bleeding events are associated with increases in short- and long-term mortality, nonfatal myocardial infarction, stroke, hospital length of stay, and hospital cost [3–11]. Despite the recent decline in clinically significant major bleeding events, the likelihood of short- and long-term consequences has remained proportional to the frequency of events [12]. Bleeding events can be generally classified into access site bleeding and non-access site bleeding. Access site bleeding for TF patients can range from a small, self-limited hematoma to a large, hemodynamically significant retroperitoneal hematoma. In a retrospective cohort analysis by Kinnaird et al. of 10,974 patients undergoing PCI [4], the incidence of Thrombolysis In Myocardial Infarction (TIMI) major bleeding was 5.4 % (n=588) and TIMI minor bleeding was 12.7 % (n=1,394), with access-site bleeding comprising 79.3 % and 59.8 % of bleeding cases,
Curr Treat Options Cardio Med (2014) 16:305
Page 3 of 11, 305
respectively. Patients with major bleeding in this study had increased rates of in-hospital and annual mortality. Predictors of increased systemic bleeding complications have included age, ACS presentation, increased anticoagulation, longer times to sheath removal, and comorbidities such as renal disease and congestive heart failure [13–16]. The proportion of major bleeding events attributable to the vascular access site depends on the patient’s clinical presentation, with STEMI patients having a larger proportion of access-site bleeding compared with NSTEMI patients [2]. PCI performed for stable angina has been associated with the lowest overall bleeding rates. However, the proportion of access site bleeding events follows a different distribution, with higher rates of bleeding in the stable angina and STEMI populations compared to the NSTE-ACS population [2]. Rates of major bleeding have decreased significantly over the last few decades as the focus for PCI has shifted from efficacy to a more comprehensive emphasis on efficacy and safety. Part of this reduction in bleeding has been associated with improved miniaturization of devices, permitting most PCI procedures to be performed with 5- or 6-French sheaths as opposed to sheaths sized 9-French or greater. Most of the reduction, however, has been due to changes in periprocedural drug therapies, especially bivalirudin [17], and less to the use of either TR access or vascular closure devices (VCDs) [18]. The data for VCDs has been mixed; randomized trial data have not shown significant benefit when compared to manual compression, though observational data seem to suggest some benefit. One meta-analysis showed slight benefit with VCDs (pooled OR 0.89, 95 % CI 0.86 – 0.91) [19], whereas another meta-analysis of 30 studies involving 37,066 patients showed similar complication rates between VCDs and mechanical compression [20]. A more recent analysis of NCDR data by Marso et al. studied the effects of various bleeding avoidance strategies and found decreased rates of bleeding in patients with vascular closure devices, bivalirudin, or both when compared to patients undergoing manual compression [21].
Transradial procedures and clinical outcomes The radial approach for coronary angiography was first described in 1989 in a series of 100 patients by Campeau [22] and subsequently by Otaki [23] in 1992. It started to gain in popularity after it was described by Kiemeneij and Laarman [24, 25] in 1994 and by Lotan et al. in 1995 [26]. Historically, TR access has seen low rates of implementation within the US, though adoption of TR access has been increasing. Data from 2,820,874 patients in the NCDR CathPCI registry show that TR adoption rates have increased 16-fold over 5 years, from 1.2 % in 2007 to 16.1 % in 2012 and accounted for 6.3 % of total procedures during that time [27]. Compared with TF access, TR access was associated with a significantly lower rate of bleeding (OR 0.5, 95 % CI 0.49 – 0.54) and access site complications (OR 0.39, 95 % CI 0.31 – 0.50), differences that tracked across all significant age, sex, and comorbidity subgroups.
305, Page 4 of 11
Curr Treat Options Cardio Med (2014) 16:305 The RIVAL (Radial Versus Femoral Access for Coronary Intervention) trial [28••] was the first large-scale, multicenter international clinical trial that randomized 7,021 patients presenting with acute coronary syndrome (ACS) undergoing cardiac catheterization to either femoral (n=3,514) or radial (n=3,507) access. Approximately two-thirds of the patients underwent PCI; the definition of major bleeding used in the study was consistent with the definition used in the CURRENT-OASIS 7 trial – major bleeding was defined as bleeding that was 1) fatal, 2) required transfusion of two or more units of packed red cells, 3) caused hypotension requiring inotrope therapy, 4) needed surgical intervention, 5) caused severely disabling sequelae, 6) was intracranial or intraocular, or 7) led to a hemoglobin drop of 5 g/dL [28••]. Trial results are shown in (Fig. 1; Table 1) and revealed no advantage of radial access over femoral access but significantly lower major vascular access complications at 30 days. In addition, when bleeding was defined using a more access sitesensitive definition like the ACUITY trial definition, there was a significant reduction with radial approach. Importantly, non-access site bleeding accounted for two-thirds of overall bleeding events in the RIVAL trial, which explains, in part, the overall neutral result since radial access would only affect access-site bleeding and not non-access-site bleeding. A pre-specified post-hoc analysis of the RIVAL trial by Mehta et al. [29] assessed efficacy and bleeding outcomes among patients presenting with STEMI and found that radial access was associated with a significant reduction in 30-day mortality (Table 2). Interestingly, this occurred despite similar rates of bleeding in both the radial and femoral access groups. Because of these mixed results and the fact that the overall trial was neutral, the RIVAL trial suggests, but does not appear to prove, that radial access may have significant outcome benefits among patients with STEMI undergoing PCI (Table 2). To address this, radial access in patients undergoing primary PCI for STEMI was prospectively assessed in the RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) trial [30••], which randomized 1,001 patients presenting with STEMI to TR (n=500) or TF (501) access. The primary outcome of composite death/MI/stroke/target vessel revascularization/non-CABG bleeding occurred in 13.6 % of TR patients versus 21.0 % of TF patients (p=0.003) with decreased mortality (5.2 % vs. 9.2 %, p=0.02) and bleeding (7.8 % vs. 12.2 %, p=0.026) in the TR arm. This rate of bleeding reduction is similar to what was seen in the HORIZONS-AMI trial comparing bivalirudin to a combination of unfractionated heparin/ glycoprotein IIb/IIIa therapy [31]. There are no US-based randomized data on transradial primary PCI. There are, however, observational data. Baklanov et al. note from the NCDR CathPCI Registry that TR access in STEMI cases has increased markedly from 0.9 % of all cases to 6.4 % of all cases [32]. Although they note a modest increase in door-to-first device times (78 min vs. 74 min, pG0.001), TR access was associated with decreased bleeding (OR 0.62, 95 % CI 0.53 – 0.72, pG0.001) and lower risk of adjusted inhospital mortality (OR 0.76, 95 % CI 0.59 – 0.99, p=0.0455).
Curr Treat Options Cardio Med (2014) 16:305
Page 5 of 11, 305
Figure 1. The primary results from the RIVAL Trial show comparable rates for the primary outcome of death, myocardial infarction, stroke, or non-CABG related major bleeding (a) and non-CABG bleeding (b).
Transradial procedures and costs From a cost perspective, the clinical benefits of TR access, which have included lower access site complications, lower bleeding, and earlier ambulation and length of stay, have to be balanced against an initially steep operator learning curve, increased procedural times [33], and increased rates of crossover to femoral access [33].
305, Page 6 of 11
Curr Treat Options Cardio Med (2014) 16:305
Table 1. Primary results from the RIVAL trial Primary outcome Death/MI/ stroke/non-CABG bleeding at 30 days Secondary outcomes Death, MI, or stroke Non-CABG major bleeding Death MI Stroke Major vascular complications
Radial (n=3507)
Femoral (n=3514)
128 (3.7 %)
139 (4.0 %)
0.92 (0.72–1.17)
112 24 44 60 20 49
114 33 51 65 14 131
0.98 0.73 0.86 0.92 1.43 0.37
(3.2 (0.7 (1.3 (1.7 (0.6 (1.4
%) %) %) %) %) %)
(3.2 (0.9 (1.5 (1.9 (0.4 (3.7
%) %) %) %) %) %)
Hazard Ratio (9 5 % CI)
(0.76–1.28) (0.43–1.23) (0.58–1.29) (0.65–1.31) (0.72–2.83) (0.27–0.52)
p-value 0.50
0.90 0.23 0.47 0.65 0.30 G0.0001
Applegate et al. evaluated the effects and cost-effectiveness of transitioning a cardiac catheterization laboratory from a “femoral first” approach to a “radial first” approach in a propensity-matched patient cohort, finding marginally higher cost for diagnostic catheterization but a $732 cost savings for TR PCI, mostly attributed to a decrease in access site complications [34]. A retrospective cohort analysis using data from the Premier research database performed propensity matching on 609 (0.1 % of the study population) TR PCI cases with 60,900 TF PCI cases and examined cost differences between the study groups, finding lower adjusted total costs by $553 in the TR PCI group, driven primarily by a 0.3 day reduction in length of stay and bleeding complications [35]. This difference was more pronounced in patients at higher risks of bleeding. A cost-benefit analysis from a meta-analysis of 14 previous studies of TR access showed that TR cases cost $275 less than TF cases from a hospital perspective [33]. Amin et al. performed a detailed cost analysis using a retrospective cohort of 7,121 procedures at five US hospitals, of which 1,219 (17 %) were TR [36•]. TR patients had a lower length of stay and decreased bleeding events and were associated with a cost savings of $830 per patient, with a graded increase of savings to $1,630 in patients with highest risk of bleeding. Procedural costs were similar between the two approaches, implying most of the cost savings was attributed to decreased length of stay. Given the current bundled payment reimbursement structure adopted by the Centers for Medicare and Medicaid Services (CMS), there may be a significant value proposition with increased adoption of TR access, providing a safer therapy (with decreased bleeding) with decreased cost, driven primarily from shorter hospital length of stay[37].
Volume-outcome relationship in TR PCI There has been a long-described relationship between the inverse relationship of volume of a particular procedure and its associated outcomes [38]. This is particularly apt in the setting of transradial PCI. It should be
(0.83–1.48) 0.491 0.025 (0.91–1.71) 0.176 0.011 (0.35–1.23) 0.190 0.557 (0.29–0.58) G0.001 0.624 (0.94–2.92) 0.082 0.001 (0.69–1.53) 0.903 0.269 (0.67–3.30) 0.335 0.864 (0.26–0.55) G0.001 0.885 1.11 1.25 0.66 0.41 1.66 1.03 1.48 0.38 (3.46) (2.71) (0.96) (4.46) (0.76) (1.87) (0.40) (3.82) 87 68 24 112 19 47 10 96 (3.84) (3.37) (0.63) (1.84) (1.25) (1.92) (0.59) (1.45) 98 86 16 47 32 49 15 37 0.026 0.031 0.870 0.009 0.006 0.225 0.696 0.002 (0.38–0.94) (0.36–0.95) (0.36–2.39) (0.28–0.84) (0.20–0.76) (0.30–1.33) (0.35–4.84) (0.19–0.70) 0.60 0.59 0.92 0.49 0.39 0.63 1.30 0.36 52 (5.19) 46 (4.59) 9 (0.91) 41 (4.10) 32 (3.19) 18 (1.82) 4 (0.40) 35 (3.49) (3.14) (2.72) (0.84) (1.99) (1.26) (1.16) (0.53) (1.26) 30 26 8 19 12 11 5 12 Primary outcome Death, MI or stroke Non-CABG major bleed ACUITY major bleed Death MI Stroke Major vascular access site complication
NSTE-ACS p Value Radial Femoral HR (n=2,552) (n=2,511) (95 % CI) STEMI Radial Femoral HR (n=955) (n=1,003) (95 % CI)
Table 2. Subgroup analysis from the RIVAL Trial of patients with STEMI
p Value p-interaction
Curr Treat Options Cardio Med (2014) 16:305
Page 7 of 11, 305 noted that the procedural success in the large clinical trials has been in the setting of experienced operators in high-volume TR centers. Operators in the RIVAL trial, for example, performed a median 300 PCIs per year (IQR 190 – 400) with 40 % (IQR 25 – 70 %) performed via the TR route [28••]. Subgroup analysis showed significant interaction between the primary composite outcome and radial PCI volume by center (HR 0.49, 95 % CI 0.28 – 0.87, p-interaction=0.021). Further analyses of outcomes stratified by PCI center volume showed a reduction in death/MI/stroke (HR 0.50, 95 % CI 0.27 – 0.92, p=0.027, p-interaction=0.013) and major vascular complications (HR 0.18, 95 % CI 0.08 – 0.37, pG0.00, p-interaction=0.019). This volume-outcome relationship also extends to safety parameters related to the radial approach – namely, the potentially increased radiation exposure compared with the femoral approach. Studies have consistently shown that the radial approach is associated with longer fluoroscopy times and radiation exposure; however, more detailed analyses suggest that these differences are dependent on operator and center proficiency. A substudy of the RIVAL trial assessed radiation differences between patients undergoing TR versus TF access [39•]. Although fluoroscopy time was noted to be higher in the TR arm (9.3 vs. 8.0 min, p G0.001), there was only a small difference in median air kerma (1,046 vs. 930 mGy, p=0.051) and no difference in median dose area product (DAP) (52.8 Gy-cm2 vs 51.2 Gy-cm2, p=0.83). However, when stratified according to center procedural volume, there was a marked increase in air kerma among the lowest volume centers, with no significant differences between radial and femoral access among high volume radial sites or operators. Similarly, Lo et al. prospectively studied the effects of operator experience and radiation exposure by measuring differences in radiation exposure by TR or TF access routes among a total of 100 cases performed by experts (91,000 procedures and 90 % of cases performed at the particular access site) versus intermediate trainee cardiologists (500 – 1,000 procedures and equal frequencies among the different access sites) [40]. Among the expert interventionalists they found an increase in procedure time with TR access but no differences in operator or patient radiation exposure. Among the trainee cardiologists, although there was no difference in procedure time or operator or patient radi-
305, Page 8 of 11
Curr Treat Options Cardio Med (2014) 16:305 ation exposure between access sites, there was a 25 % increase in operator exposure and a 10 – 15 % increase in patient exposure. These data demonstrate that that when controlling for operator and center radial proficiency, there is likely no increase in radiation exposure for neither patient nor operator, although there is a learning curve needed to achieve expertise in TR PCI.
Transradial learning curve The number of cases needed to achieve proficiency defines the so-called learning curve. Studies have described a learning curve with respect to TR PCI, showing an improvement in rates of procedural success, fluoroscopy times, and contrast utilization with increasing operator volume [41, 42]. However, this learning curve may not be as steep as previously thought. Ball et al. analyzed single center data consisting of 1,672 single vessel PCIs and stratified by operator volume [41]. They note a steep learning curve with no significant further reduction in TR failure rate after only 50 cases with only small changes in other procedural outcomes such as fluoroscopy time, contrast use, and vascular complications. Rao and Krucoff [43] have advocated the development of a “radial first” program in order to develop comfort and competency with regard to TR procedures not only by the operator but also by the nursing and support staff. Then, once there is comfort and expertise with TR access in the lowerrisk population, there should be in improved effort and commitment to consider the use of TR PCI on all eligible patients regardless of acuity. It should be noted that a “radial first” program is not a “radial only” program and there are important patient characteristics and clinical situations that would dictate use of a TF approach.
Conclusion Major, clinically significant bleeding is a common though largely avoidable complication of PCI. Nevertheless, it is still responsible for significant short- and long-term morbidity and mortality. The use of TR access in the United States, though initially low, has increased markedly over the previous 5 years and will likely continue to do so as operators become more experienced with the procedure. Large randomized data have shown similar outcomes to TF PCI but with lower vascular access complications. More recent trial data suggests mortality benefit in the STEMI population in addition to reduced bleeding and vascular complications. Although previously associated with high rates of procedural failure and increased radiation to the patient and the operator, more recent observational and trial data have failed to show significant difference, especially as operators become more proficient. Emerging data also show reduced cost with TR PCI, mostly related to decreased hospital length-of-stay and reduced bleeding complications. The benefits of TR access will likely increase operator adoption and proficiency increases so the technique can be used safely and effectively on the patient popula-
Curr Treat Options Cardio Med (2014) 16:305
Page 9 of 11, 305
tion at highest risk for bleeding complication, thus attenuating the “risktreatment paradox.”
Compliance with Ethics Guidelines Conflict of Interest Dr. Amit N. Vora declares no potential conflicts of interest relevant to this article. Dr. Sunil V. Rao reports consulting (modest) from The Medicines Company. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
2.
3.
4.
5.
6.
7.
8.
Go AS et al. Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6–e245. Rao SV et al. The transradial approach to percutaneous coronary intervention: historical perspective, current concepts, and future directions. J Am Coll Cardiol. 2010;55(20):2187–95. Batchelor WB et al. Contemporary outcome trends in the elderly undergoing percutaneous coronary interventions: results in 7,472 octogenarians. National Cardiovascular Network Collaboration. J Am Coll Cardiol. 2000;36(3):723–30. Kinnaird TD et al. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions. Am J Cardiol. 2003;92(8):930–5. Lauer MA et al. Practice patterns and outcomes of percutaneous coronary interventions in the United States: 1995 to 1997. Am J Cardiol. 2002;89(8):924–9. Popma JJ et al. Vascular complications after balloon and new device angioplasty. Circulation. 1993;88(4 Pt 1):1569–78. Manoukian SV 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(12):1362–8. Pinto DS et al. Economic evaluation of bivalirudin with or without glycoprotein IIb/IIIa inhibition ver-
9.
10.
11.
12.
13.
14.
sus heparin with routine glycoprotein IIb/IIIa inhibition for early invasive management of acute coronary syndromes. J Am Coll Cardiol. 2008;52(22):1758–68. Aronow HD et al. Predictors of length of stay after coronary stenting. Am Heart J. 2001;142(5):799– 805. Cohen DJ et al. Economic evaluation of bivalirudin with provisional glycoprotein IIB/IIIA inhibition versus heparin with routine glycoprotein IIB/IIIA inhibition for percutaneous coronary intervention: results from the REPLACE-2 trial. J Am Coll Cardiol. 2004;44(9):1792–800. Lopes RD et al. Advanced age, antithrombotic strategy, and bleeding in non-ST-segment elevation acute coronary syndromes: results from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. J Am Coll Cardiol. 2009;53(12):1021–30. Nathan S, Rao SV. Radial versus femoral access for percutaneous coronary intervention: implications for vascular complications and bleeding. Curr Cardiol Rep. 2012;14(4):502–9. Doyle BJ et al. Major femoral bleeding complications after percutaneous coronary intervention: incidence, predictors, and impact on long-term survival among 17,901 patients treated at the Mayo Clinic from 1994 to 2005. JACC Cardiovasc Interv. 2008;1(2):202–9. Feit F et al. Predictors and impact of major hemorrhage on mortality following percutaneous coronary
305, Page 10 of 11 intervention from the REPLACE-2 Trial. Am J Cardiol. 2007;100(9):1364–9. 15. Kirtane AJ et al. Correlates of bleeding events among moderate- to high-risk patients undergoing percutaneous coronary intervention and treated with eptifibatide: observations from the PROTECT-TIMI30 trial. J Am Coll Cardiol. 2006;47(12):2374–9. 16. Mehta SK et al. Bleeding in patients undergoing percutaneous coronary intervention: the development of a clinical risk algorithm from the National Cardiovascular Data Registry. Circ Cardiovasc Interv. 2009;2(3):222–9. 17. Stone GW et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006;355(21):2203–16. 18. Subherwal S et al. Temporal trends in and factors associated with bleeding complications among patients undergoing percutaneous coronary intervention: a report from the National Cardiovascular Data CathPCI Registry. J Am Coll Cardiol. 2012;59(21):1861–9. 19. Vaitkus PT. A meta-analysis of percutaneous vascular closure devices after diagnostic catheterization and percutaneous coronary intervention. J Invasive Cardiol. 2004;16(5):243–6. 20. Nikolsky E et al. Vascular complications associated with arteriotomy closure devices in patients undergoing percutaneous coronary procedures: a meta-analysis. J Am Coll Cardiol. 2004;44(6):1200–9. 21. Marso SP et al. Association between use of bleeding avoidance strategies and risk of periprocedural bleeding among patients undergoing percutaneous coronary intervention. JAMA. 2010;303(21):2156–64. 22. Campeau L. Percutaneous radial artery approach for coronary angiography. Cathet Cardiovasc Diagn. 1989;16(1):3–7. 23. Otaki M. Percutaneous transradial approach for coronary angiography. Cardiology. 1992;81(6):330–3. 24. Kiemeneij F, Laarman GJ. Percutaneous transradial artery approach for coronary Palmaz-Schatz stent implantation. Am Heart J. 1994;128(1):167–74. 25. Kiemeneij F, Laarman GJ, de Melker E. Transradial artery coronary angioplasty. Am Heart J. 1995;129(1):1–7. 26. Lotan C et al. Transradial approach for coronary angiography and angioplasty. Am J Cardiol. 1995;76(3):164–7. 27. Feldman DN et al. Adoption of radial access and comparison of outcomes to femoral access in percutaneous coronary intervention: an updated report from the national cardiovascular data registry (20072012). Circulation. 2013;127(23):2295–306. 28.•• Jolly SS et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised,
Curr Treat Options Cardio Med (2014) 16:305 parallel group, multicentre trial. Lancet. 2011;377(9775):1409–20. The RIVAL Trial is the largest randomized trial comparing the transfemoral and transradial approaches to catheterization. 29. Mehta SR et al. Effects of radial versus femoral artery access in patients with acute coronary syndromes with or without ST-segment elevation. J Am Coll Cardiol. 2012;60(24):2490–9. 30.•• Romagnoli E et al. Radial versus femoral randomized investigation in ST-segment elevation acute coronary syndrome: the RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) study. J Am Coll Cardiol. 2012;60(24):2481–9. The RIFLE-STEACS is one of the largest trials specifically looking at the use of transradial access in patients presenting with ST-elevation myocardial infarction. 31. Stone GW et al. Bivalirudin during Primary PCI in Acute Myocardial Infarction. N Engl J Med. 2008;358(21):2218–30. 32. Baklanov DV et al. The prevalence and outcomes of transradial percutaneous coronary intervention for STsegment elevation myocardial infarction: analysis from the National Cardiovascular Data Registry (2007 to 2011). J Am Coll Cardiol. 2013;61(4):420–6. 33. Mitchell MD et al. Systematic review and cost-benefit analysis of radial artery access for coronary angiography and intervention. Circ Cardiovasc Qual Outcomes. 2012;5(4):454–62. 34. Applegate R, et al. Cost effectiveness of radial access for diagnostic cardiac catheterization and coronary intervention. Catheter Cardiovasc Interv. 2013;82(4):E375–84. 35. Safley DM et al. Comparison of costs between transradial and transfemoral percutaneous coronary intervention: a cohort analysis from the Premier research database. Am Heart J. 2013;165(3):303–9 e2. 36.• Amin AP, et al. Costs of Transradial Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2013;6(8):827–34. This is a retrospective study assessing cost differences between transradial and transfemoral access, describing the potential costs savings from transradial access, predominantly due to a shorter length of stay. 37. Rao SV, Patel MR. The Value Proposition in Percutaneous Coronary Intervention. J Am Coll Cardiol Intv. 2013;6(8):835–7. 38. McGrath PD et al. RElation between operator and hospital volume and outcomes following percutaneous coronary interventions in the era of the coronary stent. JAMA. 2000;284(24):3139–44. 39.• Jolly SS et al. Effect of radial versus femoral access on radiation dose and the importance of procedural volume: a substudy of the multicenter randomized RIVAL trial. JACC Cardiovasc Interv. 2013;6(3):258–66. This is a good study assessing the importance of operator volume on radiation exposure during TR catheterization.
Curr Treat Options Cardio Med (2014) 16:305 40.
41.
Lo TS et al. Impact of access site selection and operator expertise on radiation exposure; a controlled prospective study. Am Heart J. 2012;164(4):455–61. Ball WT et al. Characterization of operator learning curve for transradial coronary interventions. Circ Cardiovasc Interv. 2011;4(4):336–41.
Page 11 of 11, 305 42.
43.
Spaulding C et al. Left radial approach for coronary angiography: results of a prospective study. Cathet Cardiovasc Diagn. 1996;39(4):365–70. Rao SV, Krucoff MW. Radial first: paradox+proficiency=opportunity. J Am Heart Assoc. 2013;2(3):e000281.
