Abstract
Several factors contribute to the risk of percutaneous coronary intervention (PCI) related major entry site complications (MES). We sought to examine the trends in MES among unselected patients during the stent era. Data from the Dynamic Registry including five distinct recruitment waves from 1997 to 2006 (N=10,932) were used to assess baseline characteristics and MES among consecutive patients undergoing PCI. MES was defined as bleeding requiring transfusion, pseudoaneurysm, arterial thrombosis or dissection, vascular complication requiring surgery, or retroperitoneal bleed. Uncomplicated hematomas were not included. Several trends were observed in baseline characteristics including an increase from wave 1 to wave 5 in BMI >30 kg/m2 (30.2% to 40.4%), renal disease (3.5% to 9.1%), diabetes (28.0% to 34.1%), and hypertension (59.4% to 78%) (ptrend <0.001 for all). Use of a thienopyridine increased significantly from wave 1 (49.7%) to wave 5 (84%) whereas glycoprotein (GP) IIbIIIa inhibitor use peaked in wave 3 (53.1%) and then decreased (p<0.001). Access site was predominately femoral but radial access increased over time (0.3% wave 1, 6.6% wave 5) (p=<.0001). The rates of MES (2.8% to 2.2%, ptrend =0.01) and MES requiring transfusion (2.0% to 0.74%, ptrend <0.001) were low and decreased with time. The trend in lower risk for MES in later time periods remained after adjustment. In conclusion, MES has decreased over time however opportunity for bleeding avoidance strategies still exists.
Keywords: percutaneous coronary intervention, complications, bleeding, arterial access
Local complications at the site of vascular access are among the most common complications following percutaneous coronary intervention (PCI).1 Robust data links vascular access site complications to both morbidity and mortality following PCI.2-5 The influence of access site bleeding events and transfusion on mortality and resource utilization is particularly significant.6,7 Multiple risk factors for vascular complications following PCI have been identified, including both patient and procedural characteristics.8-10 In an attempt to minimize vascular complications associated with PCI, bleeding avoidance strategies have been advocated. Such measures include use of smaller arterial sheaths, radial artery access, use of safer and more predictable anticoagulation regimens, and closure devices.11 Data in support of these strategies are emerging. In this analysis, we sought to investigate the rates and trends in major entry site complications (MES) in a large prospective multicenter PCI Registry in order to characterize changes in patient and procedural factors and specific types of MES complications.
Methods
The National Heart, Lung, and Blood Institute (NHLBI)-sponsored Dynamic Registry was a multicenter prospective study of consecutive patients undergoing PCI in North America and has previously been described.12 The Dynamic Registry includes five distinct recruitment waves of patients enrolled from 1997 to 2006 (N=10,965). All patients enrolled in this observational study provided informed consent for inclusion of data used in this analysis. This current analysis excludes 9 patients with missing data age and 24 patients missing information on the components that define MES complications leaving a patient population of 10,932.
MES complication was defined as access site bleeding requiring transfusion, development of pseudoaneurysm, arterial thrombosis or dissection, vascular complication requiring surgery, or retroperitoneal bleeding. Uncomplicated hematomas were not included in the primary MES endpoint. Data collection for closure devices use was captured only in waves 4 and 5. Non-access site bleeding was defined as gastrointestinal bleeding, genital- urinary bleeding, or other bleeding remote from the access site. Two of the authors (JDA, KY) independently determined whether bleeding events were access or non-access site related. In the event of disagreement a third reviewer was used (FS).
PCI patients were grouped by recruitment wave and descriptive statistics were summarized as means for continuous variables and percentages for categorical variables. Differences between proportions were assessed for temporal trend using Cochran-Mantel-Haenszel or the Jonckheere-Terpstra test, where appropriate. Similar methods were used for the individual components that defined MES bleeding complications. Logistic regression was used to estimate the independent effect of clinically relevant factors on in-hospital risk of MES. Risk factors in the model included age, sex, procedural indication, cardiogenic shock, prior PCI, history of congestive heart failure, chronic kidney disease, peripheral vascular disease, GP IIbIIIa inhibitor use, access site and recruitment wave. Goodness-of-fit was assessed using the Hosmer-Lemeshow method, and the model was considered to be adequate (p>0.05). All statistical analyses were performed with the use of SAS software, version 9.3, and a two-sided p-value of 0.05 or less was considered to indicate statistical significance.
Results
Significant trends in baseline characteristics were observed with increasing comorbities over time (Table 1). The prevalence of prior myocardial infarction, however, fell over the ten year period. Significant trends in procedural characteristics were also observed (Table 2). Entry site location was predominantly femoral with increasing use of radial access over time. Anticoagulation and antiplatelet regimens varied considerably over time. Notably, use of a thienopyridine significantly increased while the use of a GP IIbIIIa inhibitor peaked in wave 3 and decreased by wave 5. Overall use of procedural and post-procedural heparin fell significantly from wave 1 to wave 5. Within the procedural period, use of unfractionated heparin fell while more low molecular weight heparin rose during the study period (ptrend<0.001 for both). Bivalirudin use, reported in waves 4 and 5 only, was 31.9% and 32.0%, respectively. Pre-procedure aspirin use was high and there was no significant change over the 10 year period. Closure devices were used in 30.9% of patients in wave 4 and 40.2% in wave 5 (p<0.001).
Table 1. Baseline characteristics of study population by recruitment wave.
| 1 | 2 | 3 | 4 | 5 | ||
|---|---|---|---|---|---|---|
| Characteristic | (N=2500) | (N=2099) | (N=2045) | (N=2111) | (N=2177) | p-value |
| Age, mean, median (years) | 62.6, 63 | 63.0, 63 | 64.4, 65 | 63.7, 64 | 63.9, 64 | <0.001 |
| Female | 35.5% | 36.4% | 36.0% | 32.5% | 32.8% | 0.005 |
| White | 80.1% | 78.2% | 79.3% | 77.0% | 75.1% | 0.99 |
| Black | 7.6% | 12.0% | 12.8% | 14.7% | 16.4% | |
| Asian | 4.8% | 3.9% | 3.8% | 3.0% | 2.2% | |
| Hispanic | 7.2% | 5.7% | 4.0% | 5.3% | 5.8% | |
| Other race/ethnicity | 0.2% | 0.2% | 0.1% | 0.0% | 0.7% | |
| Body mass index (kg/m2), mean, median | 28.2, 28 | 28.8, 28 | 29.3, 28 | 29.2, 28 | 29.6, 29 | <0.001 |
| Prior percutaneous coronary intervention | 28.5% | 30.5% | 33.0% | 31.6% | 35.2% | <0.001 |
| Prior coronary bypass | 16.6% | 17.1% | 18.6% | 19.8% | 18.0% | 0.03 |
| Prior myocardial infarction | 39.1% | 32.4% | 27.6% | 25.9% | 22.6% | <0.001 |
| Diabetes mellitus | 28.0% | 28.5% | 30.1% | 33.5% | 34.1% | <0.001 |
| Prior heart failure | 9.9% | 9.6% | 12.5% | 9.3% | 10.1% | 0.94 |
| Hypertension | 59.3% | 64.6% | 74.7% | 77.1% | 78.1% | <0.001 |
| Hypercholesterolemia | 61.0% | 63.4% | 71.4% | 74.8% | 79.1% | <0.001 |
| Smoker | ||||||
| Never | 34.5% | 32.5% | 33.2% | 37.6% | 36.0% | 0.04 |
| Current | 25.3% | 26.7% | 24.0% | 22.5% | 25.7% | |
| Former | 40.2% | 40.7% | 42.8% | 39.9% | 38.3% | |
| Renal disease | 3.5% | 5.0% | 7.3% | 8.8% | 9.2% | <0.001 |
| Peripheral vascular disease | 7.2% | 7.3% | 9.2% | 8.8% | 7.4% | 0.24 |
Baseline clinical variables were based on patient self-reports, physician diagnosis or pharmacologic therapy
Table 2. Procedural data and outcome by recruitment wave.
| 1 | 2 | 3 | 4 | 5 | ||
|---|---|---|---|---|---|---|
| Characteristic | N=2500 | N=2099 | N=2045 | N=2111 | N=2177 | p-value |
| Device access site | ||||||
| Femoral | 99.4% | 97.5% | 96.0% | 96.1% | 93.2% | <.0001 |
| Brachial | 0.3% | 0.5% | 0.2% | 0.5% | 0.2% | |
| Radial | 0.3% | 2.0% | 3.8% | 3.4% | 6.6% | |
| Meds <24hrs. Prior or During Procedure | ||||||
| Aspirin | 91.9% | 81.0% | 94.1% | 92.2% | 86.7% | 0.88 |
| Clopidogrel or Ticlopidine | 49.8% | 41.4% | 67.6% | 85.7% | 84.0% | <0.001 |
| GPIIb/IIIa inhibitor | 24.3% | 31.7% | 53.1% | 33.7% | 37.4% | <0.001 |
| Bivalirudin | - | - | - | 31.9% | 32.0% | 0.77 |
| Heparin | 97.4% | 94.6% | 95.8% | 75.6% | 71.9% | <0.001 |
| Unfractionated heparin | n/a | 93.6% | 95.0% | 73.2% | 68.8% | <0.001 |
| Low molecular weight heparin | n/a | 3.9% | 3.7% | 4.7% | 7.3% | <0.001 |
| Meds used after the procedure | ||||||
| Heparin | 38.6% | 21.6% | 10.6% | 9% | 10.6% | <.0001 |
The type of heparin used was not collected in Wave 1.
The trends in MES and bleeding outcomes are presented in Figure 1 The absolute decrease in MES over time was small but the trend was significant, from 2.8% in wave 1 to 2.2% in wave 5 (ptrend=0.015). Transfusions related to access site MES decreased over time. Among patients that experienced bleeding (n=426), the access site was the cause in 74.4%, 72.0%, 60.0%, 49.4% and 71.4% of cases in waves 1 to 5. Rates of pseudoaneurysm did not vary over time (from 0.71% in wave 1 to 0.97% in wave 5, ptrend =0.45). Complications including arterial thrombosis and surgery of the access site were rare and similar over time (data not shown).
Figure 1. Major entry site complications by recruitment wave.
Several variables were identified as independently associated with MES (Table 3). Older age, female sex, acute myocardial infarction as indication, cardiogenic shock and procedural GP IIbIIIa inhibitor use were all associated with a higher risk of MES. Prior PCI and radial access, on the other hand, were associated with a significantly lower risk of MES. Compared to recruitment wave 1, there was a trend towards a lower risk of MES in subsequent waves and this reached statistical significance in wave 4.
Table 3. Variables associated with major entry site complications in the Dynamic Registry.
| Effect | Odds Ratio | 95% Confidence Limits | p-value | |
|---|---|---|---|---|
| Age (years) | 1.037 | 1.026 | 1.049 | <0.001 |
| Female sex | 1.989 | 1.550 | 2.551 | <0.001 |
| Acute myocardial infarction* | 1.391 | 1.051 | 1.841 | 0.02 |
| Cardiogenic shock | 3.091 | 1.788 | 5.346 | <0.001 |
| Peripheral vascular disease | 1.560 | 1.072 | 2.269 | 0.02 |
| Procedural glycoprotein IIbIIIa inhibitor | 1.480 | 1.144 | 1.914 | 0.003 |
| Prior percutaneous coronary intervention | 0.696 | 0.518 | 0.936 | 0.017 |
| Radial access (versus femoral and brachial) | 0.123 | 0.017 | 0.880 | 0.037 |
| Recruitment Wave (versus wave 1) | ||||
| wave2 | 1.042 | 0.736 | 1.477 | 0.82 |
| wave3 | 0.776 | 0.534 | 1.128 | 0.18 |
| wave4 | 0.564 | 0.374 | 0.852 | 0.007 |
| wave5 | 0.756 | 0.517 | 1.105 | 0.15 |
versus other indication for percutaneous coronary intervention
Discussion
This analysis of nearly 11,000 patients in the Dynamic PCI Registry confirms a small decrease in MES complications including those requiring blood transfusion over the time period of 1998 to 2006 in unselected patients. This occurred despite an increase in high risk patient characteristics over time, including obesity, renal insufficiency, diabetes mellitus and hypertension. The improvement may be explained by the uptake of strategies known to reduce bleeding, including radial access and anticoagulation with bivalirudin, or more attentiveness to femoral arterial access, hemostasis and closure.
Our results are in keeping with other reported single center and multicenter registry analyses surveying bleeding and other vascular complications in patients undergoing PCI. In 14,239 patients undergoing PCI from the femoral artery approach at Wake Forest University, vascular complications decreased from 3.1% to 1.0% from 1998 to 2007.13 In the National Cardiovascular Data (NCDR) CathPCI Registry between 2004 and 2008 the overall rate of bleeding was 2.0%, similar to our observation. 14 In another NCDR analysis of over 1.7 million patients between 2005 and 2009, a 20% reduction in post-PCI bleeding was observed, however rates remained the highest in STEMI patients and no improvement was seen in this subgroup.15
Peri-procedural anticoagulation clearly influences MES bleeding complications. Use of alternative anticoagulants to unfractionated heparin alone or in combination with a GP IIbIIIa receptor antagonist, is associated with lower rates of bleeding complications during PCI in various patient subsets.16,17 A change in practice patterns, with the adoption of bivalirudin over time, was observed in the NCDR Cath PCI Registry with use increasing from 17% to 30% from 2005 to 2009.15 We began collecting data on bivalirudin use after wave 3, which ended in 2002. In waves 4 and 5 of the Dynamic Registry, 2004 to 2006, bivalirudin use was similar at 32%. We also observed a decline in the use of GP IIbIIIa inhibitor after 2002. Periprocedural use of a GP IIbIIIa inhibitor was found to be an independent predictor of MES in our study.
The trends we observed in radial access are also similar to other registries.15 By 2006, radial access was used in 6.6% of PCI procedures in the Dynamic Registry. This is double the rate observed in the NCDR Registry through 2009 which remained below 3%. In the subset of patients with STEMI, however, the use of radial increased from 0.9% to 6.4% from 2007 to 2011.18 The majority of randomized controlled trials supporting the radial over femoral approach for the reduction in bleeding were published later in time and may result in further increases in transradial PCI.19,20 We observed a significantly lower risk of MES in patients undergoing PCI via the radial approach. Previous trials have reported on the contribution of non-access site bleeding to major bleeding events. In the current study, the access site was responsible for bleeding in 49% to 75% of patients in each wave. An analysis of over 14,000 patients in randomized trials of PCI found that both access and non-access site bleeding were independently associated with mortality at 1 year.21
Several independent predictors of MES were identified such as female sex, peripheral vascular disease, acute myocardial infarction and cardiogenic shock. Bleeding avoidance strategies such as radial access and bivalirudin may be particularly effective at reducing bleeding complications in patients with one or more of these risk factors.
This prospective study is subject to limitations. MES was site determined and not independently adjudicated. All bleeding events however were reviewed by two of the authors to determine whether they were access or non-access site related. The severity of bleeding was not defined according to previously published criteria; however requirement of transfusion was collected. We were unable to evaluate several variables known to influence the risk of bleeding as they were not prospectively collected in the registry; including sheath size, venous access, and baseline hematocrit. Data on vascular closure device use was restricted to the later waves. Other limitations include the lack of data concerning additional techniques such as micropuncture use, and fluoroscopic or ultrasound guidance for femoral artery entry. Additionally, transfusion was at the discretion of the physicians and the threshold for transfusion may have changed over time with a higher threshold. Therefore, our results may be confounded by other factors that effectively lower MES bleeding complications and transfusions other than those explored in this analysis. Lastly, we did not assess the relationship between MES and clinical outcomes.
Acknowledgments
Funding Source: The Dynamic Registry is funded by grant HL-33292 from the National Heart, Lung and Blood Institutes of Health, Bethesda, MD.
Footnotes
Disclosures: The authors report no financial relationships or conflicts of interest
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References
- 1.Roe MT, Messenger JC, Weintraub WS, Cannon CP, Fonarow GC, Dai D, Chen AY, Klein LW, Masoudi FA, McKay C, Hewitt K, Brindis RG, Peterson ED, Rumsfeld JS. Treatments, trends, and outcomes of acute myocardial infarction and percutaneous coronary intervention. J Am Coll Cardiol. 2010;56:254–263. doi: 10.1016/j.jacc.2010.05.008. [DOI] [PubMed] [Google Scholar]
- 2.Eikelboom JW, Mehta SR, Anand SS, Xie C, Fox KAA, Yusuf S. Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation. 2006;114:774–782. doi: 10.1161/CIRCULATIONAHA.106.612812. [DOI] [PubMed] [Google Scholar]
- 3.Manoukian SV, Feit F, Mehran R, Voeltz MD, Ebrahimi R, Hamon M, Dangas GD, Lincoff AM, White HD, Moses JW, King SB, 3rd, Ohman EM, Stone GW. 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. doi: 10.1016/j.jacc.2007.02.027. [DOI] [PubMed] [Google Scholar]
- 4.Ndrepepa G, Berger PB, Mehilli J, Seyfarth M, Neumann FJ, Schomig A, Kastrati A. Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point. J Am Coll Cardiol. 2008;51:690–697. doi: 10.1016/j.jacc.2007.10.040. [DOI] [PubMed] [Google Scholar]
- 5.Doyle BJ, Rihal CS, Gastineau DA, Holmes DR., Jr Bleeding, blood transfusion, and increased mortality after percutaneous coronary intervention: implications for contemporary practice. J Am Coll Cardiol. 2009;53:2019–2027. doi: 10.1016/j.jacc.2008.12.073. [DOI] [PubMed] [Google Scholar]
- 6.Rao SV, Jollis JG, Harrington RA, Granger CB, Newby LK, Armstrong PW, Moliterno DJ, Lindblad L, Pieper K, Topol EJ, Stamler JS, Califf RM. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA. 2004;292:1555–1562. doi: 10.1001/jama.292.13.1555. [DOI] [PubMed] [Google Scholar]
- 7.Rao SV, Kaul PR, Liao L, Armstrong PW, Ohman EM, Granger CB, Califf RM, Harrington RA, Eisenstein EL, Mark DB. Association between bleeding, blood transfusion, and costs among patients with non-ST-segment elevation acute coronary syndromes. Am Heart J. 2008;155:369–374. doi: 10.1016/j.ahj.2007.10.014. [DOI] [PubMed] [Google Scholar]
- 8.Doyle BJ, Ting HH, Bell MR, Lennon RJ, Mathew V, Singh M, Holmes DR, Rihal CS. 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;1:202–209. doi: 10.1016/j.jcin.2007.12.006. [DOI] [PubMed] [Google Scholar]
- 9.Piper WD, Malenka DJ, Ryan TJ, Jr, Shubrooks SJ, Jr, O'Connor GT, Robb JF, Farrell KL, Corliss MS, Hearne MJ, Kellett MA, Jr, Watkins MW, Bradley WA, Hettleman BD, Silver TM, McGrath PD, O'Mears JR, Wennberg DE. Northern New England Cardiovascular Disease Study G. Predicting vascular complications in percutaneous coronary interventions. Am Heart J. 2003;145:1022–1029. doi: 10.1016/S0002-8703(03)00079-6. [DOI] [PubMed] [Google Scholar]
- 10.Kinnaird TD, Stabile E, Mintz GS, Lee CW, Canos DA, Gevorkian N, Pinnow EE, Kent KM, Pichard AD, Satler LF, Weissman NJ, Lindsay J, Fuchs S. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions. Am J Cardiol. 2003;92:930–935. doi: 10.1016/s0002-9149(03)00972-x. [DOI] [PubMed] [Google Scholar]
- 11.Dauerman HL, Rao SV, Resnic FS, Applegate RJ. Bleeding avoidance strategies. Consensus and controversy. J Am Coll Cardiol. 2011;58:1–10. doi: 10.1016/j.jacc.2011.02.039. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Venkitachalam L, Kip KE, Selzer F, Wilensky RL, Slater J, Mulukutla SR, Marroquin OC, Block PC, Williams DO, Kelsey SF Investigators of N-SP, Dynamic R. Twenty-year evolution of percutaneous coronary intervention and its impact on clinical outcomes: a report from the National Heart, Lung, and Blood Institute-sponsored, multicenter 1985-1986 PTCA and 1997-2006 Dynamic Registries. Circulation: Cardiovasc Interv. 2009;2:6–13. doi: 10.1161/CIRCINTERVENTIONS.108.825323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Applegate RJ, Sacrinty MT, Kutcher MA, Kahl FR, Gandhi SK, Santos RM, Little WC. Trends in vascular complications after diagnostic cardiac catheterization and percutaneous coronary intervention via the femoral artery, 1998 to 2007. JACC: Cardiovasc Interv. 2008;1:317–326. doi: 10.1016/j.jcin.2008.03.013. [DOI] [PubMed] [Google Scholar]
- 14.Marso SP, Amin AP, House JA, Kennedy KF, Spertus JA, Rao SV, Cohen DJ, Messenger JC, Rumsfeld JS. National Cardiovascular Data R. Association between use of bleeding avoidance strategies and risk of periprocedural bleeding among patients undergoing percutaneous coronary intervention. JAMA. 2010;303:2156–2164. doi: 10.1001/jama.2010.708. [DOI] [PubMed] [Google Scholar]
- 15.Subherwal S, Peterson ED, Dai D, Thomas L, Messenger JC, Xian Y, Brindis RG, Feldman DN, Senter S, Klein LW, Marso SP, Roe MT, Rao SV. 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;59:1861–1869. doi: 10.1016/j.jacc.2011.12.045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Lincoff AM, Bittl JA, Harrington RA, Feit F, Kleiman NS, Jackman JD, Sarembock IJ, Cohen DJ, Spriggs D, Ebrahimi R, Keren G, Carr J, Cohen EA, Betriu A, Desmet W, Kereiakes DJ, Rutsch W, Wilcox RG, de Feyter PJ, Vahanian A, Topol EJ Investigators R. 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. doi: 10.1001/jama.289.7.853. [DOI] [PubMed] [Google Scholar]
- 17.Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Kornowski R, Hartmann F, Gersh BJ, Pocock SJ, Dangas G, Wong SC, Kirtane AJ, Parise H, Mehran R Investigators H-AT. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med. 2008;358:2218–2230. doi: 10.1056/NEJMoa0708191. [DOI] [PubMed] [Google Scholar]
- 18.Baklanov DV, Kaltenbach LA, Marso SP, Subherwal SS, Feldman DN, Garratt KN, Curtis JP, Messenger JC, Rao SV. The prevalence and outcomes of transradial percutaneous coronary intervention for ST-segment elevation myocardial infarction: analysis from the National Cardiovascular Data Registry (2007 to 2011) J Am Coll Cardiol. 2013;61:420–426. doi: 10.1016/j.jacc.2012.10.032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Mehta SR, Jolly SS, Cairns J, Niemela K, Rao SV, Cheema AN, Steg PG, Cantor WJ, Dzavik V, Budaj A, Rokoss M, Valentin V, Gao P, Yusuf S Investigators R. Effects of radial versus femoral artery access in patients with acute coronary syndromes with or without ST-segment elevation. J Am Coll Cardiol. 2012;60:2490–2499. doi: 10.1016/j.jacc.2012.07.050. [DOI] [PubMed] [Google Scholar]
- 20.Romagnoli E, Biondi-Zoccai G, Sciahbasi A, Politi L, Rigattieri S, Pendenza G, Summaria F, Patrizi R, Borghi A, Di Russo C, Moretti C, Agostoni P, Loschiavo P, Lioy E, Sheiban I, Sangiorgi G. 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;60:281–289. doi: 10.1016/j.jacc.2012.06.017. [DOI] [PubMed] [Google Scholar]
- 21.Ndrepepa G, Neumann FJ, Richardt G, Schulz S, Tölg R, Stoyanov KM, Gick M, Ibrahim T, Fiedler KA, Berger PB, Laugwitz KL, Kastrati A. Prognostic Value of Access and Non–Access Sites Bleeding After Percutaneous Coronary Intervention. Circ Cardiovasc Interv. 2013 doi: 10.1161/CIRCINTERVENTIONS.113.000433. epub July 23, 2013. [DOI] [PubMed] [Google Scholar]