- Email: [email protected]
Comparison of low dose versus standard dose heparin for radial approach in elective coronary angiography?
International Journal of Cardiology 187 (2015) 389–392
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Comparison of low dose versus standard dose heparin for radial approach in elective coronary angiography? Ahmet Çağrı Aykan a,⁎, Tayyar Gökdeniz a, Ilker Gül a, Ezgi Kalaycıoğlu a, Mustafa Çetin a, Engin Hatem a, Ismail Gökhan Çavuşoğlu b, Can Yücel Karabay c, Ahmet Güler c, Duygun Altıntaş Aykan d, Mustafa Yıldız c a
Department of Cardiology, Ahi Evren Chest Cardiovascular Surgery Education and Research Hospital, Trabzon, Turkey Department of Radiology, Ahi Evren Chest Cardiovascular Surgery Education and Research Hospital, Trabzon, Turkey Department of Cardiology, Koşuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey d Department of Pharmacology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey b c
a r t i c l e
i n f o
Article history: Received 27 February 2014 Received in revised form 18 March 2015 Accepted 20 March 2015 Available online 21 March 2015 Keywords: Radial Angiography Occlusion Heparin Complication Sheath
a b s t r a c t Objective: The aim of this study is to evaluate the efficacy and safety of two doses of heparin, a low dose (2500 IU) and a standard dose (5000 IU) in patients who underwent transradial coronary angiography (TRCAG). Methods: A total of 459 consecutive patients were included in the present study, 217 in the 2500-IU heparin group and 242 in the 5000-IU heparin group. Radial artery patency was evaluated one month after the TRCAG with Doppler ultrasonography. Results: The RAO was observed in 15 (3.3%) patients. The RAO was significantly higher in 2500 IU heparin group than 5000 IU heparin group (5.5% vs 1.2% p = 0.010, respectively). Female gender (Odds ratio (OR) = 66.135, p = 0.002, 95% confidence interval (CI) = 4.584–954.131), sheath removal time (OR = 1.496, p b 0.001, 95% CI = 1.254–1.784) and administration of 2500 IU heparin (OR = 9.758, p = 0.034, 95% CI = 1.195–79.695) were the independent predictors of RAO in multivariate regression analysis. While the presence of hypertension was independently associated with radial artery patency in multivariate regression analysis (OR = 0.022, p = 0.005, 95% CI = 0.002–0.307). Conclusion: The patients in the standard dose heparin group had lower RAO rates compared to low dose group in this study. This suggests that using the current technique, standard dose of heparin is still required for transradial diagnostic angiography. © 2015 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Methods
Radial artery occlusion (RAO) is usually silent but an undesired complication of transradial coronary angiography (TRCAG). The reported incidence of RAO is varying [1]. The incidence of RAO is affected by many factors including patient weight, the ratio between the radial artery diameter and sheath size, repeated procedures, prolonged cannulation time, compression method, and heparin dose (1). Greater incidence of RAO was reported with the combination of low doses of heparin and occlusive radial artery compression [2,3]. However, the usage of patent hemostasis method reduces the incidence of RAO [4]. Various studies reported an association between heparin dosage and RAO. However the optimal dose of heparin administration was still debatable. In the present study, we evaluated the incidence of RAO with 2 doses of heparin, a low dose (2500 IU) and a standard dose (5000 IU) in patients who underwent TRCAG.
This prospective study was conducted at our clinic between March 2013 and November 2013. We enrolled 744 consecutive patients and randomized in a 1:1 ratio before cardiac diagnostic catheterization from the right radial artery to a low (2500 IU) or standard (5000 IU) dose of unfractionated heparin. All patients had a good pulsating radial artery and normal oximetry–plethysmography testing before TRCAG. Patients taking warfarin, with acute coronary syndrome, admitted for elective percutaneous coronary intervention, had previous TRCAG were not enrolled in this study. A total of 285 patients were excluded after diagnostic angiography when a different final dose of heparin had been administered owing to ad hoc angioplasty or in the case of conversion to another artery approach. A total of 459 patients were included in the present study, 217 in the 2500-IU group and 242 in the 5000-IU group. Informed consent was obtained from all subjects, and the investigation conforms to the principles outlined in the Declaration of Helsinki. The study protocol was approved by ethics committee. After palmar arch permeability assessment and randomization, sterile preparation and local anesthesia with 1 ml of 2% prilocain was performed. The radial artery was cannulated with 6Fr hydrophilic 10-cm-
⁎ Corresponding author at: Department of Cardiology, Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital, Soğuksu Mah, Çamlık Street, 61040 Trabzon, Turkey. E-mail address: [email protected] (A.Ç. Aykan).
http://dx.doi.org/10.1016/j.ijcard.2015.03.314 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
390
A.Ç. Aykan et al. / International Journal of Cardiology 187 (2015) 389–392
long sheaths (Glidesheath introducer, Terumo, Tokyo, Japan). After sheath insertion, a radial cocktail containing 2 mg of diltiazem, 200 mcg nitroglycerin and heparin 2500 or 5000 IU diluted in a 10-ml syringe was injected gradually through the sheath side arm into the radial artery. Coronary angiography was preferentially performed using a 6Fr Judkins left and right catheters (Boston Scientific). On completion of the diagnostic procedure, the radial sheaths were removed, and the inflatable hemostatic device was applied at the access site and after transfer to the recovery room, the initial compression was further reduced to maintain radial artery patency. Radial artery patent hemostasis was verified, first by placing a pulse oximeter on the thumb, and then observing the continuous plethysmographic signal on the monitor during manual compression of the ulnar artery just proximal to the pisiform bone. Great care was taken to obtain radial artery hemostasis while maintaining minimal pressure with the band. The band was left in place until hemostasis was completed, usually within b2 h. All patients were discharged at the same day. The radial artery patency was verified by duplex ultrasonography (Mindray M7 ultrasound system, Mİndray, Inc, Shenzen, PRC, 7L4S linear probe [5–10 mHz]) one month after the procedure. All coronary angiograms were performed by 2 interventional cardiologists with large experience in radial access. Duplex ultrasonography assessment of the radial artery was performed by 2 experienced physicians who remained unaware of the heparin dosing. Weights of the patients, in light clothes and without shoes, were measured in kilograms, and their heights were also measured. Body mass index (BMI) was calculated by dividing body weight in kilograms by the square of body height in meters. Glomerular filtration rate (GFR) was calculated according to modification in diet in renal disease formula. Hypertension was defined by a previous diagnosis of hypertension or the presence of systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥90 mm Hg (mean of two consecutive measurements). Diabetes was defined as fasting plasma glucose ≥126 mg/dl or plasma glucose level ≥ 200 mg/dl 2 h after the 75 mg oral glucose tolerance test or symptoms of hyperglycemia accompanied by casual plasma glucose ≥ 200 mg/dl or HbA1C ≥ 6.5% or patients using antidiabetic medications. Dyslipidemia was defined as total cholesterol value N200 mh/dl or usage of statin and/or fibrate. Patients who self-reported as having smoked during the previous six months were classified as smokers. Venous blood samples were drawn after a 12-hour overnight fast. Serum glucose and triglycerides were determined using standard automatic enzymatic methods. High density lipoprotein (HDL) cholesterol was determined after specific precipitation and low density lipoprotein (LDL) cholesterol was determined by the Friedewald formula.
the 5000-IU group. The characteristics of patients are shown in Table 1. The mean age of the patients was similar in both groups. Prevalence of hypertension, diabetes mellitus, dyslipidemia and smoking in both groups were similar. The procedure time, fluoroscopy time and sheath removal time were similar in both groups. While the fasting glucose, HDL, triglyceride, creatinine and eGFR levels were similar in both groups, the LDL cholesterol levels were significantly higher in the 5000 IU heparin group than in the 2500 IU heparin group (147.86 ± 42.03 mg/dl vs 138.70 ± 41.89 mg/dl). The RAO was observed in 15 (3.3%) patients. The RAO was significantly higher in the 2500 IU heparin group than in the 5000 IU heparin group (5.5% vs 1.2% p = 0.010 respectively). None of the patients had major bleeding. Table 2 summarizes the procedural and clinical data for radial artery patent (RAP) and RAO groups. Prevalence of diabetes mellitus, dyslipidemia and smoking in both groups were similar. The mean age, laboratory data, procedure time and fluoroscopy time were similar in both groups. There were significantly more women in the RAO group than in the RAP group (53.3% vs 21.6%, p = 0.008, respectively). Hypertension was significantly common among patients in the RAP than in the RAO group (54.3% vs. 26.7%, p = 0.035, respectively) while the dyslipidemia was significantly lower (59.5% vs 86.7%, p = 0.034). Sheath removal time was significantly longer in the RAO group than in the RAP group (12 (5) min vs 33 (14) min, p b 0.001, respectively). Heparin dose was also significantly different for the two groups. (See Table 3.) Female gender (Odds ratio (OR) = 66.135, p = 0.002, 95% confidence interval (CI) = 4.584–954.131), sheath removal time (OR = 1.496, p b 0.001, 95% CI = 1.254–1.784) and administration of 2500 IU heparin (OR = 9.758, p = 0.034, 95% CI = 1.195–79.695) were the independent predictors of RAO in multivariate regression analysis. While the presence of hypertension was independently associated with radial artery patency in multivariate regression analysis (OR = 0.022, p = 0.005, 95% CI = 0.002–0.307).
4. Discussion In the present study we have shown that female sex, sheath removal time and heparin dosage were the independent predictors of RAO. While the presence of hypertension was associated with radial artery patency. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL) and radial versus femoral randomized investigation in ST-elevation acute coronary
Table 1 The patient characteristics.
2.1. Statistical analysis
Variable
2500 IU Heparin n = 217
5000 IU Heparin n = 242
p
SPSS 17.0 statistical software (SPSS Inc., Chicago, Ill., USA) was used for statistical analysis. Continuous variables were expressed as means ± SD, and categorical variables were expressed as percentages. The Kolmogorov–Smirnov test was used to test the normality of distribution of continuous variables. Group means for continuous variables were compared using Student's t test and the Mann–Whitney U test as appropriate. Categorical variables were compared using the Chi square test. Multivariate logistic regression analysis was performed to find the independent predictors of RAO. Sex, presence of hypertension and dyslipidemia, sheath removal time and heparin group were entered to multivariate regression analysis. A value of p b 0.05 was considered statistically significant.
Male, n% Age, year Body mass index, kg/m2 Hypertension, n% Dyslipidemia, n% Diabetes Mellitus, n% Smoking, n% Glucose, mg/dl High density lipoprotein cholesterol, mg/dl Low density lipoprotein cholesterol, mg/dl Triglyceride, mg/dl Creatinine, mg/dl Glomerular filtration rate, ml/min Fluoroscopy time, sc Procedure time, min Sheath removal time, min Hematoma, n% Radial artery occlusion, n%
160 (73.7%) 58.85 ± 9.82 27.35 ± 4.24 119 (54.8%) 121 (55.8%) 40 (18.4%) 84 (38.7%) 103 (20) 43.08 ± 10.85
195 (80.6%) 60.72 ± 10.63 27.65 ± 4.19 126 (52.1%) 156 (64.5%) 54 (22.3%) 104 (43%) 103 (22) 42.28 ± 9.68
0.080 0.052 0.445 0.552 0.057 0.304 0.354 0.696 0.408
138.70 ± 41.89
147.86 ± 42.03
0.020
140 (98) 0.89 ± 0.23 90.4 (30.7) 150 (79.5) 7 (2) 12 (5) 0 12 (5.5%)
142.5 (84) 0.90 ± 0.26 90.3 (34.5) 142.5 (75.3) 6.5 (2) 12 (7) 5 (2.1%) 3 (1.2%)
0.850 0.449 0.982 0.065 0.391 0.732 0.063 0.010
3. Results A total of 459 (355 male) patients were included in the present study, 217 (160 male) in the 2500-IU group and 242 (195 male) in
A.Ç. Aykan et al. / International Journal of Cardiology 187 (2015) 389–392 Table 2 Clinical and laboratory data of patients. Variable
RAP, n = 444
RAO, n = 15
Male, n (%) Age, year Body mass index, kg/m2 Hypertension, n (%) Dyslipidemia, n (%) Diabetes Mellitus, n (%) Smoking, n (%) Glucose, mg/dl High density lipoprotein cholesterol, mg/dl Low density lipoprotein cholesterol, mg/dl Triglyceride, mg/dl Creatinine, mg/dl Glomerular filtration rate, ml/min Fluoroscopy time, sec Procedure time, min Sheath removal time, min Heparin group Heparin 2500 IU, n (%) Heparin 5000 IU, n (%)
348 (78.4%) 59.83 ± 10.34 27.50 ± 4.19 241 (54.3%) 264 (59.5%) 91 (20.5%) 184 (41.4%) 103 (21) 42.74 ± 10.33
7 (46.7%) 60.00 ± 8.82 27.73 ± 4.97 4 (26.7%) 13 (86.7%) 3 (20%) 4 (26.7%) 103 (21) 39.44 ± 6.98
p 0.008 0.950 0.838 0.035 0.034 0.963 0.252 0.941 0.094
143.16 ± 43.33
154.43 ± 36.62
0.309
140 (89.75) 0.90 ± 0.25 90.7 (34.5) 146 (72.8) 6.5 (2) 12 (5)
143 (134) 0.87 ± 0.19 79.5 (28.1) 145 (107) 7 (2) 33 (14)
205 (94.5%) 239 (98.8%)
12 (5.5%) 3 (1.2%)
0.237 0.747 0.179 0.983 0.659 b0.001 0.010
syndrome (RIFLE-STEACS) studies have shown significant clinical benefits in terms of both lower morbidity and cardiac mortality in patients with ST-segment elevation acute coronary syndrome [5,6]. RAO has been recognized as a most frequent complication of TRCAG [7]. Hand has dual blood supply from ulnar and radial arteries and usually collateral blood supply is enough from contralateral artery in case of occlusion. Therefore most of the RAO were unrecognized due to its silent course. Only few cases of RAO become symptomatic requiring mechanical intervention [8–10]. However the RAO limits the future transradial interventions. Varying incidence of RAO was reported in the literature ranging from b 1 to N30% [7,11,12]. RAO was found in 3.3% in the present study. Occlusion of the radial artery during hemostasis increases the RAO but patent hemostasis provides an incremental decrease in RAO [5]. Spaulding et al. reported that heparin dose of 2000–3000 IU was associated with 24% incidence of RAO whereas 5000 IU dose was related to 4.3% of RAO [2]. However the radial catheters removed by occlusive radial artery compression method which increases the RAO is compared to the patent hemostasis method. In the present study similar to Spaulding et al. we used 6Fr radial artery catheters but the incidence of RAO was lower than their study as the incidence of RAO was 5.5% in 2500 IU heparin group and 1.2% in 5000 IU heparin group in our study. This may be attributable to patent hemostasis method of radial artery catheter removal. Additionally the procedures we performed by very experienced operators in this study and the mean fluoroscopy and procedure times were very low. Furthermore the sheath removal time after the TRCAG was considerably lower than the literature. Our results have suggested that with current modern techniques of hemostasis anticoagulation with 5000 IU of heparin is still associated with significantly lower risks of RAO compared to a 2500 IU regimen and combination of faster sheath removal and standard anticoagulation with 5000 IU heparin may decrease the incidence of RAO despite using 6Fr radial artery sheaths and catheters. Only 5
391
patients in the 5000 IU heparin group had hematoma but it was not significantly different. The route of heparin administration either intravenous or through the sheath has similar RAO rates [13]. We used the arterial route in this study. The sheath size and sheath to artery ratio are important predictors of RAO [1,14]. Thus lower diameter catheters are favored against 6Fr catheters. However our results were comparable with 5Fr catheters for RAO rates. This may be attributable to faster sheath removal times and patent hemostatsis method in this study. Pancholy et al. reported that maintenance of radial artery patency during hemostasis is the most important parameter to decrease the risk of RAO and in selected cases, provisional use of heparin appears feasible and safe when patent hemostasis is maintained [15]. Additionally they reported that administration of heparin was not a predictor of late radial artery occlusion as similar occlusion rates were observed in priori and provisional heparin groups [15]. Bernat et al. studied the incidence of RAO with 2000 and 5000 IU heparin dosage regimens after TRCAG and evaluated the efficacy and safety of transient homolateral ulnar artery compression to achieve acute radial artery recanalization [12]. The RAO was not significantly higher in the 2000 IU heparin group (5.9%) than in the 5000 IU heparin group (2.9%). However the response to ulnar compression was significantly higher among patients in the 5000 IU heparin group. Schiano et al. studied the RAO related outcomes of weight adjusted heparin dose in 162 patients that underwent TRCAG [16]. They reported that weight adjusted heparinization (50 IU/kg maximum 5000 IU) had decreased radial artery compression time without causing an increase in RAO. Additionally none of the patients had RAO. The present study differs from Schiano et al.'s study that we dicotomized patients to standard 2500 and 5000 IU heparin group irrespective of their body weight. As small body stature is related to lower radial artery diameter and increased RAO rates [1]. The BMI of patients was similar in our study. Women are at increased risk for RAO after TRCAG and this finding is associated with short body stature [1]. In the present study we found that women were at greatly increased risk for RAO. Buturak et al. reported that the presence of hypertension was associated with radial artery patency after TRCAG [14]. Similar to their findings we found that the presence of hypertension is associated with radial artery patency. This may be attributable to increased arterial stiffness that may preclude the total disruption of arterial flow during compression and providing a well patent hemostasis.
4.1. Limitations This study has several limitations. Firstly the study population was relatively small. The lower sheath diameters are associated with lower RAO rates but we used 6Fr sheaths for TRCAG. Therefore the adaptation of these findings to lower sheath size may overestimate the RAO rates of lower doses in lower sheath diameters. Additionally the procedures were performed by experienced operators. All patients were pretreated with acetyl salicylic acid and continued then after. Thus effect of acetyl salicylic acid pretreatment could not be excluded.
5. Conclusion
Table 3 The independent predictors of radial artery occlusion. Variable
Odds ratio
p
95% confidence interval
Female Hypertension Dyslipidemia Sheath removal time Heparin 2500 IU
66.135 0.022 10.312 1.496 9.758
0.002 0.005 0.079 b0.001 0.034
4.584–954.131 0.002–0.307 760–139.917 1.254–1.784 1.195–79.695
The patients in the standard dose heparin group had lower RAO rates compared to low dose group in this study. This suggests that using the current technique, standard dose of heparin is still required for transradial diagnostic angiography.
Acknowledgments None declared.
392
A.Ç. Aykan et al. / International Journal of Cardiology 187 (2015) 389–392
References [1] M. Hamon, C. Pristipino, C. Di Mario, J. Nolan, J. Ludwig, M. Tubaro, M. Sabate, J. Mauri-Ferré, K. Huber, K. Niemelä, M. Haude, W. Wijns, D. Dudek, J. Fajadet, F. Kiemeneij, European Association of Percutaneous Cardiovascular Interventions, Working Group on Acute Cardiac Care of the European Society of Cardiology, Working Group on Thrombosis on the European Society of Cardiology, Consensus document on the radial approach in percutaneous cardiovascular interventions: position paper by the European Association of Percutaneous Cardiovascular Interventions and Working Groups on Acute Cardiac Care and Thrombosis of the European Society of Cardiology, EuroIntervention 8 (11) (2013) 1242–1251. [2] C. Spaulding, T. Lefevre, F. Funck, B. Thebault, M. Chauveau, K. Ben Hamda, Y. Chalet, H. Monsegu, O. Tsocanakis, A. Py, N. Guillard, S. Weber, Left radial approach for coronary angiography: results of a prospective study, Catheter. Cardiovasc. Diagn. 39 (1996) 365–370. [3] P.R. Stella, F. Kiemeneij, G.J. Laarman, D. Odekerken, T. Slagboom, R. van der Wieken, Incidence and outcome of radial artery occlusion following transradial artery coronary angioplasty, Catheter. Cardiovasc. Diagn. 40 (1997) 156–158. [4] S. Pancholy, J. Coppola, T. Patel, M. Roke-Thomas, Prevention of radial artery occlusion-patent hemostasis evaluation trial (PROPHET study): a randomized comparison of traditional versus patency documented hemostasis after transradial catheterization, Catheter. Cardiovasc. Interv. 72 (2008) 335–340. [5] S.S. Jolly, S. Yusuf, J. Cairns, K. Niemelä, D. Xavier, P. Widimsky, A. Budaj, M. Niemelä, V. Valentin, B.S. Lewis, A. Avezum, P.G. Steg, S.V. Rao, P. Gao, R. Afzal, C.D. Joyner, S. Chrolavicius, S.R. Mehta, RIVAL trial group, Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomized, parallel group, multicentre trial, Lancet 377 (2011) 1409–1420. [6] E. Romagnoli, G. Biondi-Zoccai, A. Sciahbasi, L. Politi, S. Rigattieri, G. Pendenza, F. Summaria, R. Patrizi, A. Borghi, C. Di Russo, C. Moretti, P. Agostoni, P. Loschiavo, E. Lioy, I. Sheiban, G. Sangiorgi, 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. 60 (2012) 2481–2489.
[7] I. Bernat, O.F. Bertrand, R. Rokyta, M. Kacer, J. Pesek, J. Koza, M. Smid, H. Bruhova, G. Sterbakova, L. Stepankova, O. Costerousse, Efficacy and safety of transient ulnar artery compression to recanalize acute radial artery occlusion after transradial catheterization, Am. J. Cardiol. 107 (2011) 1698–1701. [8] S.B. Pancholy, Transradial access in an occluded radial artery: new technique, J. Invasive Cardiol. 19 (2007) 541–544. [9] Z. Ruzsa, L. Pinter, R. Kolvenbach, Anterograde recanalisation of the radial artery followed by transradial angioplasty, Cardiovasc. Revasc. Med. 11 (2010) 1–4. [10] A. Babunashvili, D. Dundua, Recanalization and reuse of early occluded radial artery within 6 days after previous transradial diagnostic procedure, Catheter. Cardiovasc. Interv. 77 (2011) 530–536. [11] M. Uhlemann, S. Mobius-Winkler, M. Mende, I. Eitel, G. Fuernau, M. Sandri, V. Adams, H. Thiele, A. Linke, G. Schuler, S. Gielen, The Leipzig prospective vascular ultrasound registry in radial artery catheterization impact of sheath size on vascular complications, JACC Cardiovasc. Interv. 5 (2012) 36–43. [12] I. Bernat, O.F. Bertrand, R. Rokyta, M. Kacer, J. Pesek, J. Koza, M. Smid, H. Bruhova, G. Sterbakova, L. Stepankova, O. Costerousse, Efficacy and safety of transient ulnar artery compression to recanalize acute radial artery occlusion after transradial catheterization, Am. J. Cardiol. 107 (2011) 1698–1701. [13] S.B. Pancholy, Comparison of the effect of intra-arterial versus intravenous heparin on radial artery occlusion after transradial catheterization, Am. J. Cardiol. 104 (2009) 1083–1085. [14] A. Buturak, S. Gorgulu, T. Norgaz, N. Voyvoda, Y. Sahingoz, A. Degirmencioglu, S. Dagdelen, The long term incidence and predictors of radial artery occlusion following a transradial coronary procedure, Cardiol. J. (Jan 10 2014)http://dx.doi.org/10. 5603/CJ.a2013.0128. [15] S.B. Pancholy, O.F. Bertrand, T. Patel, Comparison of a priori versus provisional heparin therapy on radial artery occlusion after transradial coronary angiography and patent hemostasis (from the PHARAOH Study), Am. J. Cardiol. 110 (2) (2012) 173–176. [16] P. Schiano, F. Barbou, M.C. Chenilleau, J. Louembe, J. Monsegu, Adjusted weight anticoagulation for radial approach in elective coronarography: the AWARE coronarography study, EuroIntervention 6 (2) (2010) 247–250.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Comparison of low dose versus standard dose heparin for radial approach in elective coronary angiography? Ahmet Çağrı Aykan a,⁎, Tayyar Gökdeniz a, Ilker Gül a, Ezgi Kalaycıoğlu a, Mustafa Çetin a, Engin Hatem a, Ismail Gökhan Çavuşoğlu b, Can Yücel Karabay c, Ahmet Güler c, Duygun Altıntaş Aykan d, Mustafa Yıldız c a
Department of Cardiology, Ahi Evren Chest Cardiovascular Surgery Education and Research Hospital, Trabzon, Turkey Department of Radiology, Ahi Evren Chest Cardiovascular Surgery Education and Research Hospital, Trabzon, Turkey Department of Cardiology, Koşuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey d Department of Pharmacology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey b c
a r t i c l e
i n f o
Article history: Received 27 February 2014 Received in revised form 18 March 2015 Accepted 20 March 2015 Available online 21 March 2015 Keywords: Radial Angiography Occlusion Heparin Complication Sheath
a b s t r a c t Objective: The aim of this study is to evaluate the efficacy and safety of two doses of heparin, a low dose (2500 IU) and a standard dose (5000 IU) in patients who underwent transradial coronary angiography (TRCAG). Methods: A total of 459 consecutive patients were included in the present study, 217 in the 2500-IU heparin group and 242 in the 5000-IU heparin group. Radial artery patency was evaluated one month after the TRCAG with Doppler ultrasonography. Results: The RAO was observed in 15 (3.3%) patients. The RAO was significantly higher in 2500 IU heparin group than 5000 IU heparin group (5.5% vs 1.2% p = 0.010, respectively). Female gender (Odds ratio (OR) = 66.135, p = 0.002, 95% confidence interval (CI) = 4.584–954.131), sheath removal time (OR = 1.496, p b 0.001, 95% CI = 1.254–1.784) and administration of 2500 IU heparin (OR = 9.758, p = 0.034, 95% CI = 1.195–79.695) were the independent predictors of RAO in multivariate regression analysis. While the presence of hypertension was independently associated with radial artery patency in multivariate regression analysis (OR = 0.022, p = 0.005, 95% CI = 0.002–0.307). Conclusion: The patients in the standard dose heparin group had lower RAO rates compared to low dose group in this study. This suggests that using the current technique, standard dose of heparin is still required for transradial diagnostic angiography. © 2015 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Methods
Radial artery occlusion (RAO) is usually silent but an undesired complication of transradial coronary angiography (TRCAG). The reported incidence of RAO is varying [1]. The incidence of RAO is affected by many factors including patient weight, the ratio between the radial artery diameter and sheath size, repeated procedures, prolonged cannulation time, compression method, and heparin dose (1). Greater incidence of RAO was reported with the combination of low doses of heparin and occlusive radial artery compression [2,3]. However, the usage of patent hemostasis method reduces the incidence of RAO [4]. Various studies reported an association between heparin dosage and RAO. However the optimal dose of heparin administration was still debatable. In the present study, we evaluated the incidence of RAO with 2 doses of heparin, a low dose (2500 IU) and a standard dose (5000 IU) in patients who underwent TRCAG.
This prospective study was conducted at our clinic between March 2013 and November 2013. We enrolled 744 consecutive patients and randomized in a 1:1 ratio before cardiac diagnostic catheterization from the right radial artery to a low (2500 IU) or standard (5000 IU) dose of unfractionated heparin. All patients had a good pulsating radial artery and normal oximetry–plethysmography testing before TRCAG. Patients taking warfarin, with acute coronary syndrome, admitted for elective percutaneous coronary intervention, had previous TRCAG were not enrolled in this study. A total of 285 patients were excluded after diagnostic angiography when a different final dose of heparin had been administered owing to ad hoc angioplasty or in the case of conversion to another artery approach. A total of 459 patients were included in the present study, 217 in the 2500-IU group and 242 in the 5000-IU group. Informed consent was obtained from all subjects, and the investigation conforms to the principles outlined in the Declaration of Helsinki. The study protocol was approved by ethics committee. After palmar arch permeability assessment and randomization, sterile preparation and local anesthesia with 1 ml of 2% prilocain was performed. The radial artery was cannulated with 6Fr hydrophilic 10-cm-
⁎ Corresponding author at: Department of Cardiology, Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital, Soğuksu Mah, Çamlık Street, 61040 Trabzon, Turkey. E-mail address: [email protected] (A.Ç. Aykan).
http://dx.doi.org/10.1016/j.ijcard.2015.03.314 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
390
A.Ç. Aykan et al. / International Journal of Cardiology 187 (2015) 389–392
long sheaths (Glidesheath introducer, Terumo, Tokyo, Japan). After sheath insertion, a radial cocktail containing 2 mg of diltiazem, 200 mcg nitroglycerin and heparin 2500 or 5000 IU diluted in a 10-ml syringe was injected gradually through the sheath side arm into the radial artery. Coronary angiography was preferentially performed using a 6Fr Judkins left and right catheters (Boston Scientific). On completion of the diagnostic procedure, the radial sheaths were removed, and the inflatable hemostatic device was applied at the access site and after transfer to the recovery room, the initial compression was further reduced to maintain radial artery patency. Radial artery patent hemostasis was verified, first by placing a pulse oximeter on the thumb, and then observing the continuous plethysmographic signal on the monitor during manual compression of the ulnar artery just proximal to the pisiform bone. Great care was taken to obtain radial artery hemostasis while maintaining minimal pressure with the band. The band was left in place until hemostasis was completed, usually within b2 h. All patients were discharged at the same day. The radial artery patency was verified by duplex ultrasonography (Mindray M7 ultrasound system, Mİndray, Inc, Shenzen, PRC, 7L4S linear probe [5–10 mHz]) one month after the procedure. All coronary angiograms were performed by 2 interventional cardiologists with large experience in radial access. Duplex ultrasonography assessment of the radial artery was performed by 2 experienced physicians who remained unaware of the heparin dosing. Weights of the patients, in light clothes and without shoes, were measured in kilograms, and their heights were also measured. Body mass index (BMI) was calculated by dividing body weight in kilograms by the square of body height in meters. Glomerular filtration rate (GFR) was calculated according to modification in diet in renal disease formula. Hypertension was defined by a previous diagnosis of hypertension or the presence of systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥90 mm Hg (mean of two consecutive measurements). Diabetes was defined as fasting plasma glucose ≥126 mg/dl or plasma glucose level ≥ 200 mg/dl 2 h after the 75 mg oral glucose tolerance test or symptoms of hyperglycemia accompanied by casual plasma glucose ≥ 200 mg/dl or HbA1C ≥ 6.5% or patients using antidiabetic medications. Dyslipidemia was defined as total cholesterol value N200 mh/dl or usage of statin and/or fibrate. Patients who self-reported as having smoked during the previous six months were classified as smokers. Venous blood samples were drawn after a 12-hour overnight fast. Serum glucose and triglycerides were determined using standard automatic enzymatic methods. High density lipoprotein (HDL) cholesterol was determined after specific precipitation and low density lipoprotein (LDL) cholesterol was determined by the Friedewald formula.
the 5000-IU group. The characteristics of patients are shown in Table 1. The mean age of the patients was similar in both groups. Prevalence of hypertension, diabetes mellitus, dyslipidemia and smoking in both groups were similar. The procedure time, fluoroscopy time and sheath removal time were similar in both groups. While the fasting glucose, HDL, triglyceride, creatinine and eGFR levels were similar in both groups, the LDL cholesterol levels were significantly higher in the 5000 IU heparin group than in the 2500 IU heparin group (147.86 ± 42.03 mg/dl vs 138.70 ± 41.89 mg/dl). The RAO was observed in 15 (3.3%) patients. The RAO was significantly higher in the 2500 IU heparin group than in the 5000 IU heparin group (5.5% vs 1.2% p = 0.010 respectively). None of the patients had major bleeding. Table 2 summarizes the procedural and clinical data for radial artery patent (RAP) and RAO groups. Prevalence of diabetes mellitus, dyslipidemia and smoking in both groups were similar. The mean age, laboratory data, procedure time and fluoroscopy time were similar in both groups. There were significantly more women in the RAO group than in the RAP group (53.3% vs 21.6%, p = 0.008, respectively). Hypertension was significantly common among patients in the RAP than in the RAO group (54.3% vs. 26.7%, p = 0.035, respectively) while the dyslipidemia was significantly lower (59.5% vs 86.7%, p = 0.034). Sheath removal time was significantly longer in the RAO group than in the RAP group (12 (5) min vs 33 (14) min, p b 0.001, respectively). Heparin dose was also significantly different for the two groups. (See Table 3.) Female gender (Odds ratio (OR) = 66.135, p = 0.002, 95% confidence interval (CI) = 4.584–954.131), sheath removal time (OR = 1.496, p b 0.001, 95% CI = 1.254–1.784) and administration of 2500 IU heparin (OR = 9.758, p = 0.034, 95% CI = 1.195–79.695) were the independent predictors of RAO in multivariate regression analysis. While the presence of hypertension was independently associated with radial artery patency in multivariate regression analysis (OR = 0.022, p = 0.005, 95% CI = 0.002–0.307).
4. Discussion In the present study we have shown that female sex, sheath removal time and heparin dosage were the independent predictors of RAO. While the presence of hypertension was associated with radial artery patency. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL) and radial versus femoral randomized investigation in ST-elevation acute coronary
Table 1 The patient characteristics.
2.1. Statistical analysis
Variable
2500 IU Heparin n = 217
5000 IU Heparin n = 242
p
SPSS 17.0 statistical software (SPSS Inc., Chicago, Ill., USA) was used for statistical analysis. Continuous variables were expressed as means ± SD, and categorical variables were expressed as percentages. The Kolmogorov–Smirnov test was used to test the normality of distribution of continuous variables. Group means for continuous variables were compared using Student's t test and the Mann–Whitney U test as appropriate. Categorical variables were compared using the Chi square test. Multivariate logistic regression analysis was performed to find the independent predictors of RAO. Sex, presence of hypertension and dyslipidemia, sheath removal time and heparin group were entered to multivariate regression analysis. A value of p b 0.05 was considered statistically significant.
Male, n% Age, year Body mass index, kg/m2 Hypertension, n% Dyslipidemia, n% Diabetes Mellitus, n% Smoking, n% Glucose, mg/dl High density lipoprotein cholesterol, mg/dl Low density lipoprotein cholesterol, mg/dl Triglyceride, mg/dl Creatinine, mg/dl Glomerular filtration rate, ml/min Fluoroscopy time, sc Procedure time, min Sheath removal time, min Hematoma, n% Radial artery occlusion, n%
160 (73.7%) 58.85 ± 9.82 27.35 ± 4.24 119 (54.8%) 121 (55.8%) 40 (18.4%) 84 (38.7%) 103 (20) 43.08 ± 10.85
195 (80.6%) 60.72 ± 10.63 27.65 ± 4.19 126 (52.1%) 156 (64.5%) 54 (22.3%) 104 (43%) 103 (22) 42.28 ± 9.68
0.080 0.052 0.445 0.552 0.057 0.304 0.354 0.696 0.408
138.70 ± 41.89
147.86 ± 42.03
0.020
140 (98) 0.89 ± 0.23 90.4 (30.7) 150 (79.5) 7 (2) 12 (5) 0 12 (5.5%)
142.5 (84) 0.90 ± 0.26 90.3 (34.5) 142.5 (75.3) 6.5 (2) 12 (7) 5 (2.1%) 3 (1.2%)
0.850 0.449 0.982 0.065 0.391 0.732 0.063 0.010
3. Results A total of 459 (355 male) patients were included in the present study, 217 (160 male) in the 2500-IU group and 242 (195 male) in
A.Ç. Aykan et al. / International Journal of Cardiology 187 (2015) 389–392 Table 2 Clinical and laboratory data of patients. Variable
RAP, n = 444
RAO, n = 15
Male, n (%) Age, year Body mass index, kg/m2 Hypertension, n (%) Dyslipidemia, n (%) Diabetes Mellitus, n (%) Smoking, n (%) Glucose, mg/dl High density lipoprotein cholesterol, mg/dl Low density lipoprotein cholesterol, mg/dl Triglyceride, mg/dl Creatinine, mg/dl Glomerular filtration rate, ml/min Fluoroscopy time, sec Procedure time, min Sheath removal time, min Heparin group Heparin 2500 IU, n (%) Heparin 5000 IU, n (%)
348 (78.4%) 59.83 ± 10.34 27.50 ± 4.19 241 (54.3%) 264 (59.5%) 91 (20.5%) 184 (41.4%) 103 (21) 42.74 ± 10.33
7 (46.7%) 60.00 ± 8.82 27.73 ± 4.97 4 (26.7%) 13 (86.7%) 3 (20%) 4 (26.7%) 103 (21) 39.44 ± 6.98
p 0.008 0.950 0.838 0.035 0.034 0.963 0.252 0.941 0.094
143.16 ± 43.33
154.43 ± 36.62
0.309
140 (89.75) 0.90 ± 0.25 90.7 (34.5) 146 (72.8) 6.5 (2) 12 (5)
143 (134) 0.87 ± 0.19 79.5 (28.1) 145 (107) 7 (2) 33 (14)
205 (94.5%) 239 (98.8%)
12 (5.5%) 3 (1.2%)
0.237 0.747 0.179 0.983 0.659 b0.001 0.010
syndrome (RIFLE-STEACS) studies have shown significant clinical benefits in terms of both lower morbidity and cardiac mortality in patients with ST-segment elevation acute coronary syndrome [5,6]. RAO has been recognized as a most frequent complication of TRCAG [7]. Hand has dual blood supply from ulnar and radial arteries and usually collateral blood supply is enough from contralateral artery in case of occlusion. Therefore most of the RAO were unrecognized due to its silent course. Only few cases of RAO become symptomatic requiring mechanical intervention [8–10]. However the RAO limits the future transradial interventions. Varying incidence of RAO was reported in the literature ranging from b 1 to N30% [7,11,12]. RAO was found in 3.3% in the present study. Occlusion of the radial artery during hemostasis increases the RAO but patent hemostasis provides an incremental decrease in RAO [5]. Spaulding et al. reported that heparin dose of 2000–3000 IU was associated with 24% incidence of RAO whereas 5000 IU dose was related to 4.3% of RAO [2]. However the radial catheters removed by occlusive radial artery compression method which increases the RAO is compared to the patent hemostasis method. In the present study similar to Spaulding et al. we used 6Fr radial artery catheters but the incidence of RAO was lower than their study as the incidence of RAO was 5.5% in 2500 IU heparin group and 1.2% in 5000 IU heparin group in our study. This may be attributable to patent hemostasis method of radial artery catheter removal. Additionally the procedures we performed by very experienced operators in this study and the mean fluoroscopy and procedure times were very low. Furthermore the sheath removal time after the TRCAG was considerably lower than the literature. Our results have suggested that with current modern techniques of hemostasis anticoagulation with 5000 IU of heparin is still associated with significantly lower risks of RAO compared to a 2500 IU regimen and combination of faster sheath removal and standard anticoagulation with 5000 IU heparin may decrease the incidence of RAO despite using 6Fr radial artery sheaths and catheters. Only 5
391
patients in the 5000 IU heparin group had hematoma but it was not significantly different. The route of heparin administration either intravenous or through the sheath has similar RAO rates [13]. We used the arterial route in this study. The sheath size and sheath to artery ratio are important predictors of RAO [1,14]. Thus lower diameter catheters are favored against 6Fr catheters. However our results were comparable with 5Fr catheters for RAO rates. This may be attributable to faster sheath removal times and patent hemostatsis method in this study. Pancholy et al. reported that maintenance of radial artery patency during hemostasis is the most important parameter to decrease the risk of RAO and in selected cases, provisional use of heparin appears feasible and safe when patent hemostasis is maintained [15]. Additionally they reported that administration of heparin was not a predictor of late radial artery occlusion as similar occlusion rates were observed in priori and provisional heparin groups [15]. Bernat et al. studied the incidence of RAO with 2000 and 5000 IU heparin dosage regimens after TRCAG and evaluated the efficacy and safety of transient homolateral ulnar artery compression to achieve acute radial artery recanalization [12]. The RAO was not significantly higher in the 2000 IU heparin group (5.9%) than in the 5000 IU heparin group (2.9%). However the response to ulnar compression was significantly higher among patients in the 5000 IU heparin group. Schiano et al. studied the RAO related outcomes of weight adjusted heparin dose in 162 patients that underwent TRCAG [16]. They reported that weight adjusted heparinization (50 IU/kg maximum 5000 IU) had decreased radial artery compression time without causing an increase in RAO. Additionally none of the patients had RAO. The present study differs from Schiano et al.'s study that we dicotomized patients to standard 2500 and 5000 IU heparin group irrespective of their body weight. As small body stature is related to lower radial artery diameter and increased RAO rates [1]. The BMI of patients was similar in our study. Women are at increased risk for RAO after TRCAG and this finding is associated with short body stature [1]. In the present study we found that women were at greatly increased risk for RAO. Buturak et al. reported that the presence of hypertension was associated with radial artery patency after TRCAG [14]. Similar to their findings we found that the presence of hypertension is associated with radial artery patency. This may be attributable to increased arterial stiffness that may preclude the total disruption of arterial flow during compression and providing a well patent hemostasis.
4.1. Limitations This study has several limitations. Firstly the study population was relatively small. The lower sheath diameters are associated with lower RAO rates but we used 6Fr sheaths for TRCAG. Therefore the adaptation of these findings to lower sheath size may overestimate the RAO rates of lower doses in lower sheath diameters. Additionally the procedures were performed by experienced operators. All patients were pretreated with acetyl salicylic acid and continued then after. Thus effect of acetyl salicylic acid pretreatment could not be excluded.
5. Conclusion
Table 3 The independent predictors of radial artery occlusion. Variable
Odds ratio
p
95% confidence interval
Female Hypertension Dyslipidemia Sheath removal time Heparin 2500 IU
66.135 0.022 10.312 1.496 9.758
0.002 0.005 0.079 b0.001 0.034
4.584–954.131 0.002–0.307 760–139.917 1.254–1.784 1.195–79.695
The patients in the standard dose heparin group had lower RAO rates compared to low dose group in this study. This suggests that using the current technique, standard dose of heparin is still required for transradial diagnostic angiography.
Acknowledgments None declared.
392
A.Ç. Aykan et al. / International Journal of Cardiology 187 (2015) 389–392
References [1] M. Hamon, C. Pristipino, C. Di Mario, J. Nolan, J. Ludwig, M. Tubaro, M. Sabate, J. Mauri-Ferré, K. Huber, K. Niemelä, M. Haude, W. Wijns, D. Dudek, J. Fajadet, F. Kiemeneij, European Association of Percutaneous Cardiovascular Interventions, Working Group on Acute Cardiac Care of the European Society of Cardiology, Working Group on Thrombosis on the European Society of Cardiology, Consensus document on the radial approach in percutaneous cardiovascular interventions: position paper by the European Association of Percutaneous Cardiovascular Interventions and Working Groups on Acute Cardiac Care and Thrombosis of the European Society of Cardiology, EuroIntervention 8 (11) (2013) 1242–1251. [2] C. Spaulding, T. Lefevre, F. Funck, B. Thebault, M. Chauveau, K. Ben Hamda, Y. Chalet, H. Monsegu, O. Tsocanakis, A. Py, N. Guillard, S. Weber, Left radial approach for coronary angiography: results of a prospective study, Catheter. Cardiovasc. Diagn. 39 (1996) 365–370. [3] P.R. Stella, F. Kiemeneij, G.J. Laarman, D. Odekerken, T. Slagboom, R. van der Wieken, Incidence and outcome of radial artery occlusion following transradial artery coronary angioplasty, Catheter. Cardiovasc. Diagn. 40 (1997) 156–158. [4] S. Pancholy, J. Coppola, T. Patel, M. Roke-Thomas, Prevention of radial artery occlusion-patent hemostasis evaluation trial (PROPHET study): a randomized comparison of traditional versus patency documented hemostasis after transradial catheterization, Catheter. Cardiovasc. Interv. 72 (2008) 335–340. [5] S.S. Jolly, S. Yusuf, J. Cairns, K. Niemelä, D. Xavier, P. Widimsky, A. Budaj, M. Niemelä, V. Valentin, B.S. Lewis, A. Avezum, P.G. Steg, S.V. Rao, P. Gao, R. Afzal, C.D. Joyner, S. Chrolavicius, S.R. Mehta, RIVAL trial group, Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomized, parallel group, multicentre trial, Lancet 377 (2011) 1409–1420. [6] E. Romagnoli, G. Biondi-Zoccai, A. Sciahbasi, L. Politi, S. Rigattieri, G. Pendenza, F. Summaria, R. Patrizi, A. Borghi, C. Di Russo, C. Moretti, P. Agostoni, P. Loschiavo, E. Lioy, I. Sheiban, G. Sangiorgi, 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. 60 (2012) 2481–2489.
[7] I. Bernat, O.F. Bertrand, R. Rokyta, M. Kacer, J. Pesek, J. Koza, M. Smid, H. Bruhova, G. Sterbakova, L. Stepankova, O. Costerousse, Efficacy and safety of transient ulnar artery compression to recanalize acute radial artery occlusion after transradial catheterization, Am. J. Cardiol. 107 (2011) 1698–1701. [8] S.B. Pancholy, Transradial access in an occluded radial artery: new technique, J. Invasive Cardiol. 19 (2007) 541–544. [9] Z. Ruzsa, L. Pinter, R. Kolvenbach, Anterograde recanalisation of the radial artery followed by transradial angioplasty, Cardiovasc. Revasc. Med. 11 (2010) 1–4. [10] A. Babunashvili, D. Dundua, Recanalization and reuse of early occluded radial artery within 6 days after previous transradial diagnostic procedure, Catheter. Cardiovasc. Interv. 77 (2011) 530–536. [11] M. Uhlemann, S. Mobius-Winkler, M. Mende, I. Eitel, G. Fuernau, M. Sandri, V. Adams, H. Thiele, A. Linke, G. Schuler, S. Gielen, The Leipzig prospective vascular ultrasound registry in radial artery catheterization impact of sheath size on vascular complications, JACC Cardiovasc. Interv. 5 (2012) 36–43. [12] I. Bernat, O.F. Bertrand, R. Rokyta, M. Kacer, J. Pesek, J. Koza, M. Smid, H. Bruhova, G. Sterbakova, L. Stepankova, O. Costerousse, Efficacy and safety of transient ulnar artery compression to recanalize acute radial artery occlusion after transradial catheterization, Am. J. Cardiol. 107 (2011) 1698–1701. [13] S.B. Pancholy, Comparison of the effect of intra-arterial versus intravenous heparin on radial artery occlusion after transradial catheterization, Am. J. Cardiol. 104 (2009) 1083–1085. [14] A. Buturak, S. Gorgulu, T. Norgaz, N. Voyvoda, Y. Sahingoz, A. Degirmencioglu, S. Dagdelen, The long term incidence and predictors of radial artery occlusion following a transradial coronary procedure, Cardiol. J. (Jan 10 2014)http://dx.doi.org/10. 5603/CJ.a2013.0128. [15] S.B. Pancholy, O.F. Bertrand, T. Patel, Comparison of a priori versus provisional heparin therapy on radial artery occlusion after transradial coronary angiography and patent hemostasis (from the PHARAOH Study), Am. J. Cardiol. 110 (2) (2012) 173–176. [16] P. Schiano, F. Barbou, M.C. Chenilleau, J. Louembe, J. Monsegu, Adjusted weight anticoagulation for radial approach in elective coronarography: the AWARE coronarography study, EuroIntervention 6 (2) (2010) 247–250.