Catheterization and Cardiovascular Interventions 76:654–658 (2010)

Comparison of Bivalirudin Versus Heparin on Radial

Artery Occlusion After Transradial Catheterization
Sylvain Plante,1* MD, Warren J. Cantor,1 MD, Lorne Goldman,1 MD,
Steven Miner,1 MD, Amy Quesnelle,2 RT, Anusoumya Ganapathy,2 RT,
Abdol Popel,2 RT, and Olivier F. Bertrand,3* MD, PhD
Background: Anticoagulant therapy is required to prevent radial artery occlusion (RAO)
after transradial catheterization. There is no data comparing bivalirudin to standard
heparin. Methods: We studied 400 consecutive patients. In case of diagnostic angiog-
raphy-only (n 5 200), they received an intravenous bolus of heparin (70 U kg21) imme-
diately before sheath removal whereas in case of angiography followed by ad hoc per-
cutaneous coronary intervention (n 5 200), they received bivalirudin (bolus 0.75 mg
kg21, followed by infusion at 1.75 mg/kg/h). RAO was assessed 4–8 weeks later using
two-dimensional echography-doppler and reverse Allen’s test with pulse oximetry.
Results: At follow-up, 21 of the 400 (5.3%) patients were found to have RAO with no sig-
nificant difference between the two groups (3.5% bivalirudin vs. 7.0% heparin, P 5 0.18).
Patients with RAO had a significantly lower weight compared to patients without RAO
(78 6 13 kg vs. 86 6 18 kg, P 5 0.011). By multivariate analysis, a weight <84 kg (OR:
2.78, 95% CI 1.08–8.00, P 5 0.032) and a procedure duration
20 min (OR: 7.52, 95% CI
1.57–36.0, P 5 0.011) remained strong independent predictors of RAO. All cases of radial
occlusion were asymptomatic and without clinical sequelae. Conclusion: Delayed
administration of bivalirudin or heparin for transradial catheterization provides similar
efficacy in preventing RAO. Because of its low cost, a single bolus of heparin can be
preferred in case of diagnostic angiography whereas bivalirudin can be contemplated in
case of ad hoc percutaneous coronary intervention. VC 2010 Wiley-Liss, Inc.

Key words: CATH—diagnostic cardiac catheterization; ANGO—angiography coronary;

TRAD—transradial cath

INTRODUCTION The efficacy of bivalirudin to prevent RAO has not

been evaluated. We have compared the efficacy of hep-
Over the last 10 years, the transradial approach has
arin-only to bivalirudin-only in the prevention of RAO
been adopted by many interventional cardiologists as
after transradial catheterization.
an alternative vascular access site for coronary angiog-
raphy and percutaneous coronary intervention (PCI).
1
Clinical studies have shown that use of the radial ar- Southlake Regional Health Centre, Newmarket, Ontario,
tery access was associated with a reduction in vascular Canada
2
complications, as well as a reduction in procedure- York PCI Group, Newmarket, Ontario, Canada
3
Quebec Heart-Lung Institute, Quebec, Canada
related costs, mainly driven by early ambulation and
reduced length of stay and by a reduction in the use of Conflict of interest: There is no conflict of interest to declare
femoral closure devices [1,2]. Permanent radial artery regarding this study.
occlusion (RAO) has been previously reported as a
minor complication following transradial catheteriza- *Correspondence to: Sylvain Plante, MD, Catheterization Laborato-
ries, Southlake Regional Health Centre, 641, Davis Dr. Newmarket,
tion [3,4]. Routine administration of heparin immedi- Ontario, Canada, L3Y 2R2. E-mail: sylpla@rogers.com or Olivier
ately following cannulation of the radial artery has Bertrand, MD, PhD, Quebec Heart-Lung Institute, Quebec, Canada.
been used to reduce the risks of late radial artery E-mail: olivier.bertrand@crhl.ulaval.ca
thrombosis, with reported rates ranging from 2.8 to 9%
[4–8]. Bivalirudin with provisional glycoprotein IIb/ Received 29 March 2010; Revision accepted 14 April 2010
IIIa inhibition has been validated as a safe and cost- DOI 10.1002/ccd.22610
effective alternative to heparin and routine glycoprotein Published online 6 October 2010 in Wiley Online Library
IIb/IIIa inhibition in patients undergoing PCI [9–11]. (wileyonlinelibrary.com).

V
C 2010 Wiley-Liss, Inc.
 RAO and Transradial Catheterization 655

METHODS Statistical Analysis

Study Population Categorical variables were expressed as numbers and
We recruited 400 consecutive patients referred for percentages and continuous variables as mean  SD.
diagnostic coronary angiography and possible ad hoc Baseline and procedural characteristics were compared
PCI. Patients were invited to participate if they met the using Fischer’s exact test or Chi-square test for cate-
following criteria: (a) coronary angiography  PCI gorical variables and Student’s t test for continuous
successfully performed via a radial artery access; (b) variables. Continuous variables, such as body weight
on aspirin at the time of the procedure; (c) on clopi- and time procedure, were dichotomized, taking the best
dogrel at the time of procedure (6 hr after loading cutoff point of the receiver-operating characteristic
dose of 300 mg or 2 hr after loading dose of 600 (ROC) curves for RAO prediction. Multivariate analy-
mg). Patients were excluded if they had received intra- sis by nominal logistic regression models tested varia-
venous unfractionated heparin within 6 hr or low-mo- bles that were significant at P < 0.1 in the univariate
lecular-weight heparin within 12 hr of the procedure, analysis. The odds ratios (ORs) and their 95% confi-
were presenting with acute myocardial infarction (pri- dence intervals (CIs) were calculated. Multivariate
mary PCI), were in cardiogenic shock, if they had odds ratios are given for variables included in the mul-
known allergy to aspirin or clopidogrel, or were unable tivariate model. A P value < 0.05 was considered sig-
to attend the study follow-up visit at 4–8 weeks. The nificant. All tests were performed using JMP 7.0 soft-
study protocol was approved by the local Ethics ware (SAS Institute, Cary, NC).
Review Board. Written informed consent was obtained
in all patients before the procedure.
RESULTS
Study Design Baseline clinical and procedural data are shown in
Before the procedure, palmar arch patency was con- Table I. The two groups were well balanced, although
firmed by plethysmography and pulse oximetry meas- there was a higher proportion of smoking history in the
ured on index finger following compression of the ra- group of patients who received bivalirudin (70% vs.
dial artery [12]. Following radial artery cannulation, 58%, P ¼ 0.017). Vascular sheaths with hydrophilic
intra-arterial 2.5 mg of verapamil was administered to coating (Cook, IN) were used more frequently in the
minimize vasospasm and coronary angiography was heparin group. As expected, 6 Fr sheaths were used
performed. In case of diagnostic angiography, a single more often in the bivalirudin group undergoing PCI
intravenous bolus of heparin (70 U kg1) was adminis- compared to the heparin group undergoing diagnostic
tered immediately before sheath removal. For patients angiography. The average time delay from arterial
undergoing ad hoc PCI, an intravenous bolus of biva- puncture to administration of the antithrombotic agent
lirudin (0.75 mg kg1) was administered followed by was also significantly shorter in patients who received
infusion (1.75 mg/kg/h). Depending on the procedure heparin-only.
duration, the bivalirudin infusion could be either dis- At follow-up, the overall rate of RAO, defined by
continued after PCI completion or continued for up to absent Doppler flow and by absence of waveform on
maximum 1-hr post-PCI according to operator’s combined plethysmography/pulse oximetry, was 5.3%.
choice. After sheath removal, a bracelet (HemostopV, There was no significant difference in the incidence of
R

Zoom, Piedmont, QC, Canada) was maintained over RAO in the heparin group compared to the bivalirudin
the radial artery until hemostasis was completed usu- group (7.0% vs. 3.5%, P ¼ 0.18; Fig. 1). All cases of
ally within 2 hr as previously described for transradial radial occlusion were asymptomatic and without clini-
or transulnar catheterization [13,14]. cal sequelae. Patients with RAO at follow-up weighted
significantly less than patients without RAO and
female gender was nonsignificantly associated with
Follow-Up RAO (Table II). Although the delay between radial ar-
Clinical follow-up was performed 4–8 weeks after tery puncture and antithrombotic therapy was not related
the procedure. Radial artery patency was assessed by to the incidence of RAO, a shorter procedural duration
two-dimensional echography and pulsed Doppler and was significantly associated with RAO. By multivariate
by combined plethysmography and pulse oximetry analysis, the type of anticoagulant therapy was not an
measured on the index finger following compression of independent predictor of RAO whereas body weight
ulnar artery for 2 min (reverse Allen’s test). RAO was with a cut-off at 84 kg (OR: 2.78, 95% CI 1.08–8.00, P
defined as the absence of Doppler flow and the absence ¼ 0.032) and a procedure duration with a cutoff at 20
of waveform on the plethysmography/oxymetry test. min (OR: 7.52, 95% CI 1.57–36.0, P ¼ 0.011) were
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.
Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
656 Plante et al.

TABLE I. Baseline Clinical and Procedural Data

All Patients Bivalirudin Heparin
(n ¼ 400) (n ¼ 200) (n ¼ 200) P*
Age (years) 60  11 60  11 59  11 0.58
Male Gender 304 (76%) 156 (78%) 148 (74%) 0.41
Weight (kg) 86  18 86  19 85  16 0.84
Previous myocardial infarction 70 (18%) 34 (17%) 36 (18%) 0.90
Previous coronary artery bypass grafting 14 (4%) 6 (3%) 8 (4%) 0.79
Previous percutaneous coronary intervention 68 (17%) 37 (19%) 31 (16%) 0.51
Previous radial access 30 (8%) 16 (8%) 14 (7%) 0.85
Hydrophilic sheath 214 (54%) 85 (43%) 129 (65%) <0.0001
Sheath Size 0.0004
4 Fr 3 (0.8%) 0 (0.0%) 3 (1.5%)
5 Fr 25 (6%) 4 (2%) 21 (11%)
6 Fr 372 (93%) 196 (98%) 176 (88%)
Time from puncture to antithrombotic 13 7 14 7 12 6 0.024
therapy (min)
Data are presented as mean  standard deviation (SD) or number (percent of total).
*P value for the comparison between bivalirudin and heparin groups.

TABLE II. Characteristics of Patients With Radial Artery

Occlusion
Radial artery occlusion
Yes No
(n ¼ 21, 5.3%) (n ¼ 379, 94.7%) P
Group 0.18
Bivalirudin 7 (33%) 193 (51%)
Heparin 14 (67%) 186 (49%)
Age (years) 63  10 59  11 0.14
Male Gender 13 (62%) 291 (77%) 0.12
Weight (kg) 78  13 86  18 0.011
Diabetes 6 (29%) 71 (19%) 0.26
Smoking History 16 (76%) 238 (63%) 0.25
Previous radial access 1 (5%) 29 (8%) 1.00
Hydrophilic sheath 12 (57%) 202 (54%) 0.82
Sheath size 0.56
5 Fr 2 (10%) 23 (6%)
6 Fr 19 (90%) 353 (93%)
Fig. 1. Incidence of radial artery occlusion. Time from puncture 13  7 13  6 0.76
to anticoagulant (min)
identified as significant independent predictors of RAO Procedure duration (min) 19  13 27  18 0.017
4–8 weeks after transradial catheterization (AUC 0.72; Data are presented as mean  standard deviation (SD) or number (per-
Fig. 2). In this model, there was no interaction between cent of total).
anticoagulant therapy and procedure duration.

DISCUSSION
the early days of transradial catheterization, the use of
In this study, we showed that the choice of anticoa- heparin has been recommended to limit the risks of
gulant therapy between heparin and bivalirudin admin- early RAO [3,4,8]. More recently, pretreatment with
istered after completion of diagnostic angiography does clopidogrel was associated with less risks of RAO by
not influence the incidence of RAO after transradial univariate analysis but was not identified as independ-
catheterization. Permanent RAO after transradial cathe- ent predictor by multivariate analysis [16,17]. Apart
terization has been well documented and previously from antithrombotic therapies, several other factors
reported [3–5,7]. Although RAO is rarely associated have been shown to influence the incidence of RAO.
with significant clinical symptoms, it may limit future Saito et al. have demonstrated that a significant mis-
access if other invasive procedures are needed. match between catheter and radial artery size was asso-
Although hydrophilic sheaths have become popular to ciated with increased risk of RAO [18]. This has
increase patient comfort, they have not been associated prompted radialists to favor smaller catheter sizes for
with less risks of RAO postcatheterization [15]. Since diagnostic coronary angiography and PCI with
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.
Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
 RAO and Transradial Catheterization 657

We cannot exclude that some baseline or procedural

characteristics were different in the two groups and could
have affected the results. Ultimately only a randomized
study could determine the optimal anticoagulant therapy.
This study was conducted by operators and nursing staff
well-experienced in transradial approach, confirmation
of those results in less-experienced centers is still war-
ranted. The study compared heparin-only to bivalirudin-
only, we cannot exclude that a regimen combining hepa-
rin to bivalirudin would further reduce radial artery
occlusion. Rates of RAO were numerically lower with
bivalirudin, we cannot exclude a type I error. Finally, the
design of the study imposed to administer anticoagulant
therapy after completion of diagnostic procedure; we
cannot exclude that immediate anticoagulant therapy af-
ter sheath insertion better prevents RAO.
Fig. 2. Independent predictors of radial artery occlusion. Our study could have direct clinical implications. In
case of diagnostic procedure, a delayed administration
transradial approach. More recently, the concept of pat- of heparin may provide a safe and inexpensive antith-
ent hemostasis technique has been promoted as a sim- rombotic regimen to limit the risk of RAO after trans-
ple way of minimizing the risks of RAO [5,17]. In radial approach. Conversely, if the operator decides to
contrast, a recent study did not show benefit for intra- proceed with ad hoc PCI after completion of the diag-
arterial compared to intravenous low dose weight-based nostic angiography, he may then opt for bivalirudin
heparin delivery to limit the risks of RAO [6]. In this use and heparin can be safely omitted. Whether the
study, we could identify only two independent predic- avoidance of heparin may even reduce the risks of
tors of RAO. Lower weight has been previously associ- bleeding when bivalirudin is preferred requires further
ated with increased risk of RAO and may simply investigation.
reflect that those patients had smaller radial arteries
[5]. The association between shorter procedures and REFERENCES
RAO is more puzzling. We can only speculate that it
may be due to differences in clinical characteristics 1. Jolly SS, Amlani S, Hamon M, Yusuf S, Mehta SR. Radial versus
femoral access for coronary angiography or intervention and the
between patients undergoing angiography-only versus impact on major bleeding and ischemic events: A systematic
those undergoing angiography and ad hoc PCI. Con- review and meta-analysis of randomized trials. Am Heart J 2009;
versely, it could also suggest that prolonged anticoagu- 157:132–140.
lation could limit the risks of RAO. Furthermore, biva- 2. Mann T, Cubeddu G, Bowen J, Schneider JE, Arrowood M,
lirudin therapy is known to be associated with higher Newman WN, Zellinger MJ, Rose GC. Stenting in acute coro-
nary syndromes: A comparison of radial versus femoral access
ACT values than heparin therapy, this may have played sites. J Am Coll Cardiol 1998;32:572–576.
a role in preventing RAO [10]. 3. Kiemeneij F, Laarman GJ, Odekerken D, Slagboom T, van der
In the US, bivalirudin has become the predominant Wieken R. A randomized comparison of percutaneous translu-
antithrombotic therapy owing to the significant reduction minal coronary angioplasty by the radial, brachial and femoral
of bleeding complications compared to the standard hepa- approaches: The access study. J Am Coll Cardiol 1997;29:
1269–1275.
rin  glycoprotein IIb/IIIa receptor inhibitors [10,19,20]. 4. Stella PR, Kiemeneij F, Laarman GJ, Odekerken D, Slagboom
However, the exact benefit of bivalirudin with transradial T, van der Wieken R. Incidence and outcome of radial artery
PCI remains uncertain [21]. To date, there has been only occlusion following transradial artery coronary angioplasty.
one study evaluating the incidence of RAO after bivaliru- Cathet Cardiovasc Diagn 1997;40:156–158.
din use in patients referred for transradial catheterization 5. Pancholy S, Coppola J, Patel T, Roke-Thomas M. Prevention of
radial artery occlusion-patent hemostasis evaluation trial
with possible ad hoc PCI. Although the incidence of (PROPHET study): A randomized comparison of traditional ver-
postprocedure RAO was kept low, investigators used var- sus patency documented hemostasis after transradial catheteriza-
ious dosages of heparin on top of bivalirudin [22]. tion. Cathet Cardiovasc Interv 2008;72:335–340.
6. Pancholy SB. Comparison of the effect of intra-arterial versus
intravenous heparin on radial artery occlusion after transradial
Limitations catheterization. Am J Cardiol 2009;104:1083–1085.
7. Pancholy SB. Impact of two different hemostatic devices on ra-
This was a nonrandomized comparison between dial artery outcomes after transradial catheterization. J Invasive
patients undergoing two different types of procedures. Cardiol 2009;21:101–104.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.
Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
658 Plante et al.

8. Spaulding C, Lefevre T, Funck F, Thebault B, Chauveau M, 15. Kindel M, Ruppel R. Hydrophilic-coated sheaths increase the
Ben Hamda K, Chalet Y, Monsegu H, Tsocanakis O, Py A, success rate of transradial coronary procedures and reduce
et al. Left radial approach for coronary angiography: Results of a patient discomfort but do not reduce the occlusion rate:
prospective study. Cathet Cardiovasc Diagn 1996;39:365–370. Randomized single-blind comparison of coated vs. non-coated
9. Cohen DJ, Lincoff AM, Lavelle TA, Chen HL, Bakhai A, Bere- sheaths. Clin Res Cardiol 2008;97:609–614.
zin RH, Jackman D, Sarembock IJ, Topol EJ. Economic evalua- 16. Cubero JM, Lombardo J, Pedrosa C, Diaz-Bejarano D, Sanchez
tion of bivalirudin with provisional glycoprotein IIB/IIIA inhibi- B, Fernandez V, Gomez C, Vazquez R, Molano FJ, Pastor LF.
tion versus heparin with routine glycoprotein IIB/IIIA inhibition Radial compression guided by mean artery pressure versus
for percutaneous coronary intervention: Results from the standard compression with a pneumatic device (RACOMAP).
REPLACE-2 trial. J Am Coll Cardiol 2004;44:1792–1800. Cathet Cardiovasc Interv 2009;73:467–472.
10. Lincoff AM, Bittl JA, Harrington RA, Feit F, Kleiman NS, 17. Sanmartin M, Gomez M, Rumoroso JR, Sadaba M, Martinez
Jackman JD, Sarembock IJ, Cohen DJ, Spriggs D, Ebrahimi R, M, Baz JA, Iniguez A. Interruption of blood flow during com-
et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade pression and radial artery occlusion after transradial catheteriza-
compared with heparin and planned glycoprotein IIb/IIIa block- tion. Cathet Cardiovasc Interv 2007;70:185–189.
ade during percutaneous coronary intervention: REPLACE-2 18. Saito S, Ikei H, Hosokawa G, Tanaka S. Influence of the ratio
randomized trial. JAMA 2003;289:853–863. between radial artery inner diameter and sheath outer diameter
11. Stone GW, Ware JH, Bertrand ME, Lincoff AM, Moses JW, on radial artery flow after transradial coronary intervention.
Ohman EM, White HD, Feit F, Colombo A, McLaurin BT, Cathet Cardiovasc Interv 1999;46:173–178.
et al. Antithrombotic strategies in patients with acute coronary 19. Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM,
syndromes undergoing early invasive management: One-year Moses JW, White HD, Pocock SJ, Ware JH, Feit F, et al. Biva-
results from the ACUITY trial. JAMA 2007;298:2497–2506. lirudin for patients with acute coronary syndromes. N Engl J
12. Barbeau GR, Arsenault F, Dugas L, Simard S, Lariviere MM. Med 2006;355:2203–2216.
Evaluation of the ulnopalmar arterial arches with pulse oximetry 20. Stone GW, White HD, Ohman EM, Bertrand ME, Lincoff AM,
and plethysmography: Comparison with the Allen’s test in 1010 McLaurin BT, Cox DA, Pocock SJ, Ware JH, Feit F, et al.
patients. Am Heart J 2004;147:489–493. Bivalirudin in patients with acute coronary syndromes under-
13. Bertrand OF, De Larochelliere R, Rodes-Cabau J, Proulx G, going percutaneous coronary intervention: A subgroup analysis
Gleeton O, Nguyen CM, Dery JP, Barbeau G, Noel B, Larose from the acute catheterization and urgent intervention triage
E, et al. A randomized study comparing same-day home dis- strategy (ACUITY) trial. Lancet 2007;369:907–919.
charge and abciximab bolus only to overnight hospitalization 21. Hamon M, Rasmussen LH, Manoukian SV, Cequier A, Lincoff
and abciximab bolus and infusion after transradial coronary MA, Rupprecht HJ, Gersh BJ, Mann T, Bertrand ME, Mehran
stent implantation. Circulation 2006;114:2636–2643. R, et al. Choice of arterial access site and outcomes in patients
14. Mangin L, Bertrand OF, De La Rochelliere R, Proulx G, Lemay with acute coronary syndromes managed with an early invasive
R, Barbeau G, Gleeton O, Rodes-Cabau J, Nguyen CM, Roy L. strategy: The ACUITY trial. EuroIntervention 2009;5:115–120.
The transulnar approach for coronary intervention: A safe alter- 22. Venkatesh K, Mann T. Transitioning from heparin to bivalirudin
native to transradial approach in selected patients. J Invasive in patients undergoing ad hoc transradial interventional proce-
Cardiol 2005;17:77–79. dures: A pilot study. J Invasive Cardiol 2006;18:120–124.

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