Randomized COmparison of Isolated Radial Artery ComPrEssioN Versus Radial and Ipsilateral Ulnar Artery Compression in Achieving Radial Artery Patency: The OPEN-Radial Trial

Abstract: Background. Radial artery occlusion (RAO) occurs after transradial access (TRA), limiting future ipsilateral access. Pragmatic RAO-lowering strategies need to be developed. Methods. Patients undergoing transradial cardiac catheterization were randomized to receive postprocedural hemostasis with either a single-bladder radial compression band (group 1) or a double-balloon band capable of simultaneous ipsilateral ulnar artery compression (group 2). Hemostatic compression was performed for 120 minutes. Patients in group 2 received ipsilateral ulnar artery compression for the first 60 minutes of radial hemostasis. The primary endpoint of the study was achievement of patent hemostasis, defined as radial artery patency at 15 minutes after onset of hemostatic compression. Radial artery patency was measured at 15 minutes, 60 minutes, 90 minutes, and 120 minutes after onset of compression and 1 hour after removal of the compression bands. Results. A total of 253 patients were randomized (127 in group 1 and 126 in group 2). Patent hemostasis was achieved significantly more frequently in group 2 vs group 1 (96.8% vs 74.8%, respectively; P<.001). RAO at 1 hour post band removal was significantly lower in group 2 vs group 1 (1.6% vs 10.2%, respectively; P<.001). Rebound bleeding occurred less frequently in group 2 vs group 1 (1.6% vs 7.9%, respectively; P=.03). Conclusion. Ipsilateral ulnar compression performed for the initial 1 hour during the radial hemostatic process after TRA using a dedicated double-balloon device is associated with higher rates of patent hemostasis and lower incidence of RAO compared with a single-balloon band.

J INVASIVE CARDIOL 2020;32(12):476-482. Epub 2020 September 22. 

Key words: access approach, bleeding, hemostasis, ipsilateral access, radial access

Transradial access (TRA) has been increasingly utilized for diagnostic and interventional cardiovascular procedures over the past 2 decades.¹ The most common adverse structural consequence of radial artery puncture is radial artery occlusion (RAO), which occurs in 2%-10% of patients undergoing TRA.² Several procedural strategies, such as smaller catheter size and use of intraprocedural anticoagulation with heparin or a similar parenteral agent, have been shown to reduce the incidence of RAO.^3-5 Hemostatic compression without interruption of radial artery flow — termed “patent hemostasis” — has been shown to significantly improve postprocedural radial artery patency.^6,7 Despite its large beneficial effect and lack of adverse effects, the adoption of patent hemostasis has been low.⁸ This is likely due to the need for repeated postprocedural monitoring of radial artery patency as well as adjustments in compression pressure that are needed to properly execute a patent hemostasis protocol. Prophylactic ipsilateral ulnar artery compression has been shown to further lower the incidence of RAO after TRA, and its incremental efficacy compared with patent hemostasis has been demonstrated in both randomized and observational settings.^9,10 The lack of a dedicated device with the capability of both radial hemostasis and ipsilateral ulnar artery compression has delayed the incorporation of this practice into routine postprocedural care. In addition, the efficacy of a shorter duration of ipsilateral ulnar compression compared with the current standard of care has not been established.

We sought to evaluate patent hemostasis and RAO rates using a dedicated device capable of both ipsilateral ulnar artery compression and radial artery compression for hemostasis and compare them with a standard of care device for radial artery hemostasis.

Methods

The study was conducted at a tertiary care center in India. The protocol was reviewed and approved by the local institutional review board. Written informed consent was obtained. The trial was registered on Clinicaltrials.gov (NCT04002791).

Inclusion criteria. Patients referred for cardiac catheterization using TRA were included in the study. 

Exclusion criteria. The following patients were excluded from the study: (1) patients with history of previous ipsilateral TRA; (2) patients who received warfarin anticoagulation or on novel oral anticoagulant compounds; (3) patients requiring continuous intravenous heparin infusion for any indication; (4) patients with presence of plethysmographic waveform when both radial and ulnar arteries were occlusively compressed (suggestive of presumed interosseous artery related digital plethysmographic waveform); (5) patients with absence of palpable ulnar pulse; and (6) patients who did not provide informed consent.

Study endpoints. The primary study endpoint was achievement of patent hemostasis, defined as presence of radial artery patency at 15 minutes after onset of hemostatic compression of the radial artery, using the plethysmographic technique described below. The secondary study endpoint was RAO evaluated by plethysmographic technique, 1 hour after the removal of hemostatic compression device.

All patients underwent a Barbeau test before the procedure, although TRA was performed if inclusion criteria were met. Reverse Barbeau test was also performed before the procedure when the ipsilateral ulnar artery was transiently compressed in conjunction with radial artery compression, while plethysmographic waveform monitoring was in progress, with the sensor placed on ipsilateral index finger. Total absence of waveform while both arteries were compressed was necessary for inclusion in the trial. Upon release of the radial artery, return of the waveform was considered evidence of patency of radial artery at baseline. The randomization scheme is depicted in the CONSORT diagram shown in Figure 1. Patients randomized to group 1 received hemostasis post procedure using TR Band (Terumo Interventional Systems), while group 2 received hemostasis using the VasoBand (VASOInnovations).

Transradial procedure. The patients underwent standard preparation with infiltration of lidocaine using a 25 gauge, short needle at the distal forearm in the vicinity of the radial pulse, 2-3 finger breadths above the wrist joint. Using a micropuncture system and counterpuncture technique,¹¹ a 5 Fr, hydrophilic-coated, 7 cm Radiofocus introducer sheath (Terumo Interventional Systems) was placed in the radial artery. A vasodilator cocktail containing 200 µg of nitroglycerin and 2.5 mg of verapamil was administered intra-arterially via the introducer, and 5000 U bolus of unfractionated heparin was administered intravenously after placement of the sheath. The remainder of the procedure was completed following the standard routine, with coronary angiography performed using catheters deemed necessary by the primary operator.

Group 1 hemostasis protocol. Patients randomized to group 1 received hemostatic compression using the TR Band, which was applied by placing the green centering marker 2-3 mm proximal to the skin entry site, at the presumed arteriotomy site. After securing the band around the forearm circumferentially using Velcro, the bladder was inflated using air in a standard fashion. The introducer sheath was then gently removed and the inflated bladder was gently deflated to the point where a small amount of bleeding was noted at the skin puncture site, at which point the bladder was reinflated to achieve dry hemostasis using the lowest necessary amount of air injected into the bladder. The care team was allowed adjustment in hemostatic pressure throughout the hemostatic compression period and followed the patent hemostasis protocol. The band was left in place for a minimum duration of 120 minutes. After 120 minutes, the band bladder was gradually deflated over 15 minutes and the band was removed if there was no bleeding. Inadequate hemostasis was treated with hemostatic pressure adjustment at any time during the hemostatic process. If rebound bleeding occurred, the band was reinflated and hemostatic compression was reapplied for 30 minutes, after which the weaning process was repeated and the band was removed.

Group 2 hemostasis protocol. Patients randomized to group 2 received hemostatic compression using VasoBand, which was placed on the forearm, with the distal edge of the band aligned with the crease of the wrist. The band was secured circumferentially around the forearm using Velcro. Ulnar balloon was inflated using 15 mL of air. Radial balloon was inflated using 15-20 mL of air, the introducer sheath was removed, and the radial bladder was then deflated to observe a small amount of bleeding at the skin puncture site, after which it was inflated with the smallest necessary volume of air to achieve dry hemostasis. Ulnar balloon was deflated after 60 minutes of onset of compression by the care team. At this point, hemostatic pressure adjustment was allowed if deemed necessary by the care team. No other adjustments in hemostatic pressure were made. After 120 minutes, as per the institution’s protocol, the band compression pressure was weaned over 15 minutes and the band was removed. If rebound bleeding occurred, the band was reinflated and hemostatic compression was reapplied for 30 minutes, after which the weaning process was repeated and the band was removed. A dry dressing was applied with minimal pressure at the puncture site to cover the dermotomy. Inadequate hemostasis was treated with hemostatic pressure adjustment at any time during the hemostatic process.

Evaluation of radial artery patency. In group 1 patients, radial artery patency was evaluated by performing reverse Barbeau test. Ipsilateral ulnar artery at the distal forearm as well as the radial artery proximal to the band were occlusively compressed while observing the plethysmographic waveform with a plethysmograph sensor placed on the ipsilateral index finger. Absence of waveform was noted. Then, while transiently maintaining ulnar artery occlusive compression, radial artery was released. Presence of plethysmographic waveform was considered evidence of radial artery patency.

In group 2 patients, the plethysmographic sensor was placed on the ipsilateral index finger. Absence of waveform was considered evidence of RAO. If waveform was present, the radial artery was compressed proximal to the band in the mid-forearm, with adequate compression to eliminate the palpable pulse at that point. Absence of a plethysmographic waveform at this time confirmed occlusive ipsilateral ulnar artery compression. Upon release of radial artery compression proximal to the band in the mid-forearm region, return of plethysmographic waveform was considered evidence of radial artery patency with presence of antegrade flow.

A separate team evaluated radial artery patency after the application of the band, and at 15 minutes, 60 minutes, 90 minutes, and 120 minutes post band application. If the band compression exceeded 120 minutes, patency was evaluated at 30-minute intervals after 120 minutes. Radial artery patency was evaluated at the time of discharge, at a minimum of 60 minutes after the band was removed and the dressing was applied. Findings of radial artery patency obtained by the monitoring team were blinded from the clinical care team. The care team performed their own patency evaluation following the local “patent hemostasis” routine after onset of hemostatic compression. All equivocal plethysmographic tests were evaluated by performing radial artery duplex Doppler ultrasonography. 

Demographic, laboratory, and procedural variables were recorded upon enrollment. Postprocedural variables including systolic blood pressure, diastolic blood pressure, presence of pain at the forearm, and difficulty in hardware transit during the procedure suggestive of spasm. Occurrence of hand pain throughout the procedural, postprocedural, and predischarge course were also recorded. 

Statistical analysis. Categorical variables were expressed as proportions, and differences between the two groups were assessed using Chi-square test or Pearson’s test, as deemed appropriate. Numeric variables were assessed for normality of the distribution and were expressed as mean ± standard deviation for normally distributed variables, and median (interquartile range) for those without normal distribution. Parametric tests were used to compare differences between the two groups for normally distributed numeric variables, and non-parametric tests were used for those variables with a non-normal distribution. Paired t-test was performed to compare serial blood pressure observations. Binary logistic regression was performed to identify independent predictors of RAO. Mediation analysis was performed to identify potential mechanistic basis of the effect observed in the treatment (VasoBand) group.

Sample size calculation. Based on the available literature, using the current standard of care TR Band, sample size was calculated for achievement of patent hemostasis (our primary study endpoint, as defined above). We used an optimistic 80% patent hemostasis rate in the TR Band group in view of the high level of training of the research site in preventing RAO. The only published randomized trial using prophylactic ipsilateral ulnar artery compression during radial artery hemostatic compression has shown 96% achievement of patent hemostasis at 15 minutes after onset of compression. Using 80% rate of patent hemostasis in the single-balloon band (TR Band) group and 95% rate of patent hemostasis in the double-balloon band (VasoBand) group, a Chi-square model provided a sample size of 194 patients equally divided between the two groups as necessary to achieve a 90% power with an alpha error of .05. Average incidence of RAO 1 hour after removal of hemostatic compression device (using the findings from recent trials reporting RAO rates at <24 hours sampling),^5,9,12 RAO was expected to occur in 11% of patients in the TR Band group and 1.5% in the VasoBand group, providing a sample size of a total of 250 patients in order to have a 90% chance of detecting a difference in the secondary endpoint of RAO with an alpha of .05. It is important to note that RAO incidence is very dependent upon time of evaluation after the procedure, so data from recent studies mentioning the time point of RAO evaluation were used for sample size calculation. SPSS version 26 statistical software (IBM Corporation) was used for the analyses.

Results

Out of 287 screened patients, a total of 253 were randomized, with 127 patients in the TR Band group (group 1) and 126 patients in the VasoBand group (group 2). Four patients on oral anticoagulant therapy, 25 patients with previous ipsilateral TRA, 3 patients requiring systemic anticoagulation using unfractionated heparin infusion due to new-onset atrial fibrillation, and 2 patients with a persistent plethysmographic waveform after occlusion of both radial and ulnar arteries during preprocedural plethysmographic testing were excluded.

Baseline demographic characteristics of the study population are shown in Table 1. There were no significant differences in age, gender, history of hypertension, diabetes mellitus, peripheral vascular disease, myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, height, weight, hemoglobin, platelets, creatinine, and wrist circumference between the two groups. There were no differences in blood pressure or heart rate between the two groups during the study. There were no significant differences in forearm pain or hand pain between the two groups. Rebound bleeding was significantly lower in the VasoBand group (1.6% in group 2 vs 8.7% in group 1; P=.01). Patients randomized to VasoBand had a significantly lower rate of forearm hematoma (0.8% in group 2 vs 6.3% in group 1; P=.02) (Table 2). Table 3 and Figure 2 show the study outcome measures in the two groups. The rate of patent hemostasis at 15 minutes was significantly higher in the VasoBand group (96.8% in group 2 vs 74.8% in group 1; P<.001). The rate of RAO at discharge was significantly lower in VasoBand patients (1.6% in group 2 vs 10.2% in group 1; P<.001). 

A significant decrease in systolic blood pressure was noted at 30 minutes after onset of hemostatic compression compared with the systolic blood pressure before the procedure and at the onset of hemostasis (Supplemental Table S1 and Supplemental Figure S1; supplemental materials available at www.invasivecardiology.com). 

Univariate analysis showed allocation to VasoBand group vs TR Band group was associated with a significantly higher achievement of patent hemostasis (96.8% vs 74.8%; P<.001), a lower rate of RAO (1.6% vs 10.2%; P<.001), and a lower rate of rebound bleeding (1.6% vs 7.9%; P=.03). Multivariable analysis was performed using binary logistic regression, and when adjusted for absence of patent hemostasis (odds ratio [OR],137; 95% confidence interval [CI], 8-2357; P<.01) and rebound bleeding (OR,130.3; 95% CI, 12-1388; P<.01), the allocation to either band group ceased to be a significant predictor of RAO (OR, 2.8; 95% CI, 0.2-39; P=.44), suggesting that higher probability of patent hemostasis and reduction in rebound bleeding likely mediate the superior efficacy of VasoBand in lowering the incidence of RAO at discharge. The model demonstrated excellent statistical discrimination (c-statistic=.93). 

Discussion

Our results show that use of the dedicated double-balloon VasoBand device, which is capable of both ipsilateral ulnar artery compression and radial artery hemostatic compression, is associated with a significantly higher rate of patent hemostasis compared with the current standard of care with an isolated radial artery compression device (the TR Band). The VasoBand is also associated with a significantly lower rate of RAO at the time of discharge from the cardiac catheterization laboratory compared with the conventional patent hemostasis protocol. These results were achieved without the need for frequent monitoring of radial artery patency and adjustment of hemostatic compression pressure, as advised by the typical patent hemostasis protocol. The event rates in the control arm of our study were comparable with the patent hemostasis rates observed in other recent studies and the early RAO rates observed in these studies. 

Despite robust data supporting its efficacy in lowering RAO, patent hemostasis protocol has received limited adoption in the cardiac catheterization laboratories worldwide, hence depriving patients of its benefits.⁸ Other approaches, such as higher doses of heparin,⁵ which are expected to have undesirable systemic effects, or further miniaturization of the hardware profile,¹³ which imposes limitations on procedural capabilities, have been used to reduce the risk of RAO, and are gaining popularity. This is likely due to the lack of added contributions from the care team with these approaches in order to achieve improved radial artery outcomes. Approaches that require frequent monitoring are likely less desirable for the cardiac catheterization care team due to scarcity of skilled manpower and related costs. Our data indicate that when using ipsilateral ulnar artery compression, even when systematic frequent monitoring of radial artery patency is not performed, superior radial artery patency rates will be achieved at the time of discharge. As most radial arteries that are patent on “early” evaluation have not been found to subsequently occlude,⁹ these findings essentially imply better long-term radial artery patency with the VasoBand device compared with the TR Band.

The predominant variable in achieving hemostasis, at least in the initial part of the process, is likely the mechanical counterbalance between the force of hemostatic compression, as well as the centrifugal and circumferential forces driven by intraluminal pressure ejecting blood through the arteriotomy and the circumferential stress stretching the arteriotomy apart, respectively. When the operator applies the hemostatic compression device at the arteriotomy at the outset, compression pressure is applied with a slightly higher magnitude than the expulsive pressure coming through the arteriotomy to obtain hemostasis using the patent hemostasis protocol. The intraluminal (or systemic) blood pressure changes over the duration of hemostatic compression, frequently decreasing, as observed in our dataset, as the patient usually physically and mentally relaxes during this phase for a variety of reasons. These changes in the blood pressure likely alter the balance of forces in the radial artery at the compression site, as the extrinsic compression force remains constant. If this leads to bleeding, it is noticed and corrected by the care team, but if the balance of hemodynamics allows the extrinsic compression to be overpowering, the radial lumen is compromised and flow cessation occurs. This phenomenon is largely asymptomatic and leads to thrombus formation in the lumen due to the combination of stasis and subintimal exposure, and eventual RAO.¹⁴ This likely explains why protocols involving frequent monitoring of this milieu, such as the patent hemostasis protocol⁶ or those directly titrating compression pressure using mean arterial pressure,⁷ have shown efficacy in maintaining radial patency. Ipsilateral ulnar artery compression has been shown to increase radial artery flow,¹⁵ and likely the radius of the vessel due to flow-mediated dilation with a decrease in circumferential stress due to vessel dilation. These changes related to increased flow likely decrease the probability of flow cessation despite alteration in hemodynamics. This hypothetical mechanism is supported by our observation of a steady maintenance of radial artery patency without the need for adjustment in compression pressure in the VasoBand group throughout the hemostatic process despite the change in systemic hemodynamics. This initial gain in patency is maintained throughout the subsequent course, hence decreasing the dependence on potential spontaneous recanalization, which may eventually re-establish patency. In our adjusted analysis, patent hemostasis (defined as radial patency at 15 minutes into hemostatic compression) was identified as a mediator of the superior efficacy of VasoBand in reducing the incidence of RAO at discharge. This corroborates that patent hemostasis is the suspected mechanism of benefit of ipsilateral ulnar compression — furthermore, in this instance, without the need for meticulous and repeated monitoring and adjustment of compression pressure.

In our cohort, significantly lower incidence of rebound bleeding and hematoma was observed in the VasoBand group compared with the TR Band group. Once again, this may be the result of a complex interaction of steady hemostatic environment at the arteriotomy site provided by ipsilateral ulnar compression allowing the hemostatic thrombotic plug to better stabilize and reinforce hemostasis, due to lesser change in compression pressure. The longer length of the radial balloon in the VasoBand compared with the TR Band may have provided some compression proximal to the arteriotomy, possibly driving this result. Rebound bleeding has been found to be an independent predictor of RAO,¹⁶ as observed in our dataset as well; therefore, this difference may have caused some of the disparity in RAO rates observed between the two groups. When rebound bleeding was entered as an independent variable in the multivariable model, patent hemostasis maintained its predictive significance, indicating that in those patients who develop rebound bleeding, maintenance of patency while recompressing may be of utmost importance in reducing the incidence of RAO. No significant difference in hand discomfort (as reported by the patients) was observed between the two groups. Premature discontinuation of ipsilateral ulnar artery compression was not required in any patient in our study, thereby corroborating excellent tolerability of this technique and device.

Conclusion

Radial artery hemostasis with concomitant ipsilateral ulnar artery compression for the initial 60 minutes using a double-balloon band (VasoBand) is associated with a higher probability of achieving patent hemostasis and with higher radial artery patency at discharge compared with traditional radial-only compression (TR Band) in patients undergoing diagnostic cardiac catheterization using TRA.

Acknowledgment. The authors are grateful to Mr Yash Soni and the cardiac catheterization laboratory staff at Apex Heart Institute for their enthusiastic help with this study.  

From the Apex Heart Institute, Mondeal Business Complex, Ahmedabad, India.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript accepted June 29, 2020.

Address for correspondence: Tejas M. Patel, MD, DM, FESC, FACC, FSCAI, Chairman, Apex Heart Institute, Ahmedabad, India. Email: tejaspatel@apexheart.in 

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