Comparison of long-term radial artery occlusion via distal vs. conventional transradial access (CONDITION): a randomized controlled trial

The CONDITION (Comparison of Long-term Radial Artery OcclusiON in Coronary Diagnosis and/or Intervention Via DIstal vs. ConvenTIONal Transradial Access) study was a single-centre, prospective, randomized controlled trial. This study was approved by the Ethics Committee of Wujin Hospital Affiliated with Jiangsu University. Written informed consent was obtained from all of the patients. The study protocol was performed in accordance with the Declaration of Helsinki and was registered in ClinicalTrials.gov (Registration number: NCT05253820).

Patients who were scheduled for coronary angiography and/or intervention in the cardiovascular department of our hospital between February and December 2022 were screened. The eligibility criteria included age ≥ 18 years, palpable distal and conventional radial arteries, willingness to participate in the study and a signed informed consent form. Patients with cardiogenic shock or acute ST elevated myocardial infarction were excluded. Other exclusion criteria included age ≥ 90 years, height ≥ 185 cm, previous right radial or distal artery intervention, contraindications to puncture at the puncture site, and expected loss to follow-up. Patients who had previously undergone a right radial artery intervention and then underwent coronary artery bypass grafting (CABG) with the left internal mammary artery were also enrolled in the study due to priority of left side access (Fig. 1).

After the patients signed the informed consent forms, they were randomized in a 1:1 ratio to the dTRA or TRA group. According to the literature, patient and procedure-related factors were found to be associated with RAO after the TRA procedure [7]. Several studies have revealed that female sex is an independently predictive factor for RAO. Compared with that in males, the diameter of dTRA in females was significantly smaller, which led to more puncture failure. In addition, the small vessel leads to a higher percentage of sheath-to-vessel mismatch and increases the incidence of RAO. Therefore, we used stratified randomization by gender to reduce the impact of gender on the study. The computer-generated randomization sequence stratified patients by sex and was performed by an independent researcher. For concealed allocation, the group allocation was stored in individually sealed envelopes that were opened in sequence by the operators prior to the beginning of the procedure.

Vessel puncture was performed by five interventional cardiologists in our centre who had performed more than 500 TRA punctures and more than 50 dTRA punctures. According to the protocol of this study, the right vessel seemed to be the prior puncture site. However, in patients who had previously undergone CABG with the left internal mammary artery, the left hand was the proposed puncture site.

Patients were supine on the digital subtraction angiography examination bed. After disinfection, the right hand was placed in a natural position on the right side of the body, and the left hand was placed in the region of the right inferior abdomen. After local infiltration anaesthesia with 1–2 ml lidocaine, puncture was performed with the Seldinger method.

The details of the dTRA puncture procedure are described elsewhere [13], but briefly, the operators palpated the artery to locate the pulse and punctured the distal radial artery with a 20-gauge trocar at a 30° angle. After a successful puncture, a 6 Fr artery sheath (RADIFOCUS INTRODUCER II, Terumo, Japan) was carefully inserted into the artery.

Unlike the puncture of the distal radial artery, the TRA puncture requires the patient’s hand to be in an external rotation position, and the puncture point was located 2–3 cm proximal to the wrist stripe. The puncture method and subsequent operation were the same as those for the distal radial artery.

After a successful puncture, 3000 U of unfractionated heparin was injected immediately, and 100 U/kg was added if a coronary intervention was needed. The arterial sheath was removed immediately after the procedure. In the TRA group, haemostasis was achieved by using a compression device (TR Band, Terumo). First, approximately 14 ml of gas was injected into the airbag until the bleeding completely stopped. Then, the gas-filled bag was slowly deflated until there was minimal bleeding again. Finally, another 2 ml of gas was added. Afterwards, 2 ml of air was released every 2 h. The compressor was completely removed after 6 h for coronary angiography (CAG) and after 10 h for percutaneous coronary intervention (PCI). In the dTRA group, an elastic bandage was used to achieve haemostasis. The folded gauze was placed on the bottom of the anatomic snuffbox (AS) and wrapped with an elastic bandage. The elastic bandage was loosened after 1 h for CAG only and after 2 h for PCI and then completely withdrawn after another 2 h.

The vessel was evaluated using a portable ultrasound machine with an L18-4MH frequency probe (Konica Minolta, HS1 Plus). According to the protocol, the radial artery segment from the AS to 20 cm proximal to the styloid process of the radius was evaluated. The examination included not only the internal diameter and intima thickness of the vessels but also any vascular complications such as RAO, distal radial artery occlusion (dRAO), pseudoaneurysm or arteriovenous fistula. The ultrasound was performed by an independent assessor who was not involved in the study but had extensive experience. Ultrasound examinations were performed at three time points, 1 day prior to the cardiovascular intervention and at 24 h and 3 months after the procedure.

The primary endpoint was long-term RAO at the 3-month follow-up after the procedure. The criteria for RAO included thrombus, interrupted blood flow, and disappearance of the pulse spectrum of the artery, as shown by Doppler ultrasound (Fig. 2).

The secondary endpoints included the successful puncture rate, defined as complete insertion of the artery sheath; single puncture attempt success rate; puncture time, defined as the time from the end of local anaesthesia to the sheath completely implanted into the vessel; procedure time; fluoroscopy time; radiation dose; contrast volume; and access-related complications, such as finger numbness, pain during haemostasis, pseudoaneurysm and arteriovenous fistula, RAO and dRAO at 24 h. A modified version of the Early Discharge After Transradial Stenting of Coronary Arteries Study (mEASY) classification was used to evaluate the haematoma and the Bleeding Academic Research Consortium (BARC) criteria was used to evaluate the bleeding [14, 15]. Pain during haemostasis was assessed using the visual analogue scale (VAS). A score of 0 indicates no pain, 1–3 to mild pain, 4–6 to moderate pain, and 7–10 to severe pain [16].

According to the previous literature, the incidence of RAO in the TRA group was approximately 7.7% before discharge and decreased to 5.5% after more than 1 week of follow-up [7]. The occurrence of RAO in the dTRA group was approximately 1.7%, as previously reported [17]. We assumed that the rate of recanalization was similar between the two groups and estimated that the incidence of RAO in the dTRA group was 1.2% at the 3-month follow-up. A total of 692 participants (346 in each group) should be enrolled in the study to provide 80% power to detect the 4.3% difference in the risk of primary outcome, assuming a 20% loss to follow-up rate, at a two-sided type I error of 0.05. However, approximately 800 participants were eventually enrolled in the study to achieve greater power of testing.

The primary and secondary endpoints were analysed in both intention-to-treat (ITT) and per-protocol (PP) populations, with ITT analysis as the primary analysis. The ITT population included all patients who underwent randomization and treatment. The PP population excluded patients who were not suitable for the study protocol or were lost to follow-up. In addition, an as-treated analysis was performed as a sensitivity analysis. Post hoc analysis to the primary outcome was performed by subgroup analysis stratified by age (< 60 years or ≥ 60 years), sex (male or female), body mass index (BMI) (< 24.0 kg/m² or ≥ 24.0 kg/m²), essential hypertension (EH) (yes or no), diabetic mellitus (DM) (yes or no), atrial fibrillation (AF) (yes or no), CAG only (yes or no), radial artery diameter (< 2.3 mm or ≥ 2.3 mm). Continuous variables were expressed as the mean ± standard deviation for normally distributed data or median (interquartile range) for nonnormally distributed data, and the difference between the two groups was compared with t test or Wilcoxon rank test as appropriate. Categorical variables were expressed as numbers (percentages) and compared with the chi-square test or Fisher’s exact test. Risk ratios (RR) with 95% confidence intervals (CI) were used to compare the difference in the rate of RAO between the two groups. No imputation was performed for missing data. A two-tailed P < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS 17.0 software.

Table 1 lists the baseline characteristics of the enrolled patients. The groups were comparable in terms of demographics, preoperative vital signs, medical history and laboratory findings. There was no significant difference between the two groups in terms of medication, except for aspirin (48.4% vs. 38.2%, P < 0.01). The ejection fraction was higher in the dTRA group than in the TRA group (63.0% vs. 62.0%, P < 0.01). There was no statistically significant difference in the diameter of the conventional radial artery between the two groups. However, the diameter of the distal radial artery in the TRA group was smaller than that in the dTRA group (P < 0.05).

The procedure characteristics are shown in Table 2. The right approach was first accepted in most cases in both groups (99.8% vs. 99.2%, P = 0.31). The proportion of PCI in the dTRA group was lower than that in the TRA group (22.9% vs. 29.8%, P = 0.03). Among PCI patients, there was no difference between the two groups in the proportion of multivessel disease or the number of implanted stents and drug balloons. The proportions of coronary artery disease (54.6% vs. 50.8%, P = 0.28) and acute coronary syndrome (23.1% vs. 18.3%, P = 0.10) were similar in the two groups. The sheath crossover from 6 to 7 Fr occurred in four cases in the TRA group. To achieve successful puncture, the PTCA guide-wire assistant in the dTRA group was significantly higher than that in the TRA group (2.8% vs. 0.2%, P < 0.01). Compared with that in the TRA group, the dosage of unfractionated heparin in the dTRA group was lower (P < 0.05).

Long-term follow-up via ultrasound was obtained in 90.6% of patients in the TRA group and 90.7% of patients in the dTRA group. The characteristics of the patients who were loss-to or completed follow-up are compared in Additional file 1: Table S1.

In the ITT analysis, the incidence of RAO at 3 months was 0.8% (3/361) in the dTRA group and 3.3% (12/365) in the TRA group (RR = 0.25, 95% CI = 0.07–0.88, P = 0.02). In the PP analysis, the incidence of RAO was 0.6% (2/344) in the dTRA group and 3.4% (12/357) in the TRA group (RR = 0.17, 95% CI = 0.04–0.76, P = 0.01), which was consistent with the results of the ITT analysis (Table 3, Fig. 3).

Post Hoc analysis of the primary outcome was performed by subgroup analysis. In patients with BMI < 24.0 kg/m², the primary outcome occurred in 10 (5.0%) of 200 patients in the TRA group and 1 (0.5%) of 191 patients in the dTRA group (P = 0.007). In patients with CAG only, the primary outcome occurred in 11 (3.9%) of 284 patients in the TRA group and 2 (0.7%) of 306 patients in the dTRA group (P = 0.008) (Additional file 1: Table S2).

In the ITT analysis, the incidence of early RAO in the dTRA group was significantly lower than that in the TRA group at 24 h after the procedure (2.5% vs. 6.7%, P < 0.01). However, the incidence of dRAO was higher in the dTRA group than in the TRA group in both the early (dTRA: 2.3% vs. TRA: 0.2%, P = 0.01) and long-term (dTRA: 1.4% vs. TRA: 0.0%, P = 0.03) follow-up (Table 3).

The success rate of puncture (96.0% vs. 98.5%, P = 0.03) and single puncture attempt (70.9% vs. 83.9%, P < 0.001) was significantly lower in the dTRA group than in the TRA group. However, the number of puncture attempts and puncture time were higher in the dTRA group. There was no difference in the procedure success rate, total procedural time, or total fluoroscopy time between the two groups. Compared with the TRA group, the dTRA group had a larger contrast volume (P < 0.05).

The dTRA group had a lower incidence of bleeding than the TRA group (1.5% vs. 6.0%, P < 0.01). Additionally, the incidence of hand numbness was significantly higher in the dTRA group than in the TRA group (20.4% vs. 9.2%, P < 0.01). There were no significant differences between the two groups in terms of haematoma, pseudoaneurysm, arteriovenous fistula and pain during haemostasis. Compared with that preoperatively, the intima of the radial artery at the 3-month follow-up was significantly increased in both the dTRA group and in the TRA group. However, there was no significant difference in the change in the radial artery intima between the two groups.

In the PP analysis, most of the findings were consistent with the ITT analysis, except for the total procedural time (dTRA: 23 min vs. TRA: 30 min, P = 0.02) and the incidence of mEASY type ≥ II haematoma (dTRA: 0.3% vs. TRA: 2.0%, P = 0.04).

The results of the comparison of total procedural time and the incidence of mEASY type ≥ II haematoma between the two groups in the as-treated analysis were consistent with those of the PP analysis (Additional file 1: Table S3).

First, there was no uniform compression haemostasis between the two groups. In the present study, the TR band was used in the TRA group. Due to the lack of special haemostatic devices for dTRA, an elastic bandage was used for haemostasis in the dTRA group. Theoretically, the rate of RAO may be higher with elastic bandages than with compression devices. However, even with the use of elastic bandages for haemostasis, we found a significantly lower rate of RAO in the dTRA group than in the TRA group. That is, the rate of RAO will be lower in the dTRA group with better compression haemostasis. Second, patent haemostasis was not performed in either group, which may have also influenced the outcomes. In “real-world” practice, patent haemostasis is not always feasible in high-volume tertiary centres because it needs more human resources and time. We acknowledge the potential adverse impact without patent haemostasis, but differential bias between groups can be avoided as both TRA and dTRA groups did not use patent haemostasis in our study. Therefore, we think the impact is controllable and relatively acceptable. Third, this study was performed by physicians who were experienced in performing puncture via the TRA and dTRA, which might have increased the puncture success rate and reduced the incidence of radial artery injury. Fourth, according to the previous literature, the initially estimated sample size was 692. In 2022, two large-scale randomized controlled trials with lower difference of incidence of RAO were successively published during our study. We realized that the sample size estimates were overly optimistic in the study design. The statistical power may not be sufficient based on the original estimation protocol. Therefore, we increased the sample size to 801. The incidence of long-term RAO was 3.3% in the TRA group and 0.8% in the dTRA group in the present study as an ITT analysis. Based on the actual outcomes and sample size (801), the post hoc power of the test was only 70%. In principle, we should consider adaptive study of adjusting the sample size when we design the study. Finally, although all patients underwent ultrasound examination before the procedure, this study protocol did not limit the internal diameter of the vessel at the puncture site. As reported, the vessel diameter in AS is significantly smaller than that in conventional radial artery puncture sites, and small vessels may reduce the puncture success rate and increase the risk of RAO [7, 34, 35]. Therefore, preoperative assessment of the internal diameter of the artery by ultrasound and choosing the appropriate patients might further reduce the incidence of RAO.