Transradial access (TRA) is the preferred vascular access method for diagnostic and therapeutic cardiac catheterization [1,2]. Its superiority stems from lower rates of bleeding and major vascular access complications, as well as improved patient comfort compared to transfemoral access [3-5]. Despite these advantages, TRA can be associated with radial artery occlusion (RAO), a relatively common but often overlooked complication [6].

RAO occurs in up to 38% of cases and can be immediate (7.7% within the first 24 hours) or delayed (5.8% at 30 days of follow-up) [6,7]. The dual blood supply to the hand and the rich network of collateral circulation with multiple anastomoses often result in asymptomatic RAO. Consequently, it is overlooked by over 50% of operators, and radial artery patency is often not assessed before discharge [8]. However, radial artery patency is critical for potential future catheterization procedures, coronary bypass surgery, and arteriovenous fistula formation for hemodialysis [1,9,10].

Strategies proposed to prevent RAO include the use of smaller sheaths, anticoagulants or statins, post-procedure compression, and heparinization [6,11-13]. However, RAO rates of 7%-12% have still been reported despite these preventive measures [14]. Previous studies have primarily focused on the prevention of RAO, with limited data on the role of different anticoagulation regimens in its resolution.

This pilot randomized controlled trial (RCT) aimed to evaluate the efficacy and safety of two anticoagulation strategies—subcutaneous enoxaparin versus oral rivaroxaban—for the resolution of symptomatic post-catheterization RAO in patients undergoing diagnostic cardiac catheterization.

This single-center, prospective, pilot RCT was conducted between January 2022 and December 2023. Patients who developed symptomatic RAO following diagnostic cardiac catheterization via TRA were screened for eligibility. RAO was defined as the complete absence of blood flow (i.e., total thrombotic occlusion) on Doppler ultrasound within 24 hours post-procedure.

Considering the potential risk of bleeding and the pilot nature of this study, only patients undergoing diagnostic catheterization without the need for dual antiplatelet therapy (DAPT) were included. Additional exclusion criteria were contraindications to anticoagulation, high bleeding risk, other indications for anticoagulation, and the need for DAPT. Coronary angiography was performed using the radial approach according to the latest recommendation [15]. Notably, 5,000 IU of unfractionated heparin was administered as a peri-catheterization anticoagulation strategy for patients with successful radial access [16].

Within the first 24 hours post-catheterization, all symptomatic patients who underwent cardiac catheterization via the radial approach were examined by treating physicians. Patients with a disturbed Allen test or loss of radial artery pulse, with or without pain at the access site, were evaluated using Doppler ultrasonography. Eligible participants were randomly assigned (1:1 ratio) to receive either subcutaneous enoxaparin (1 mg/kg twice daily) for 28 days or oral rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg daily for 7 days). The choice of anticoagulants was based on their availability in the country. Considering the acute thrombotic nature of RAO, therapeutic dosing (similar to that used for venous thromboembolism) was selected for both regimens [17].

Based on the available evidence, spontaneous RAO recanalization typically occurs within 1-3 months after the procedure. To minimize the risk of bleeding complications associated with prolonged anticoagulation, a 28-day anticoagulation therapy was chosen for this trial [18,19]. Permuted block randomization with a block size of four was performed using an electronic randomization system.

All patients underwent weekly phone interviews to assess potential complications, treatment adherence, and clinical symptoms. Doppler ultrasonography of the radial access site was performed 4 weeks after treatment initiation to evaluate radial artery patency, which was graded as total occlusion (echogenic thrombotic material with flow absence), partial occlusion (intraluminal thrombosis with reduced but discernible flow), or complete resolution (no thrombotic material with normal flow). All ultrasound examinations were performed by a single radiologist (KRK) with expertise in vascular diseases.

The primary outcome was Doppler ultrasonography-based radial artery patency. The main safety outcome was major bleeding, classified according to the International Society of Thrombosis and Hemostasis criteria for non-surgical patients. Major bleeding events were defined as fatal bleeding, symptomatic bleeding in a critical area or organ (e.g., intracranial, spinal, ocular, retroperitoneal, pericardial, intra-articular, or intramuscular bleeding with compartment syndrome), or bleeding causing a fall in hemoglobin level of 2 g/L or greater or requiring transfusion of two or more units of packed red blood cells within a 48-hour period [20].

Baseline characteristics were summarized using the median (interquartile range, IQR) for continuous variables and frequencies/percentages for categorical variables. Comparisons between the two groups were made using the unpaired Student t-test or Mann–Whitney U-test for continuous variables and the chi-square or Fisher exact test for categorical variables. The primary and secondary outcomes, including complete or partial recanalization and safety endpoints, were analyzed using odds ratios with 95% confidence intervals (CIs). Missing data were managed by excluding patients who did not complete follow-up.

All statistical analyses were performed using IBM SPSS Statistics ver. 27.0 (IBM). A two-tailed P-value <0.05 was considered statistically significant. Given the small sample size, the results were interpreted with caution, emphasizing effect sizes and CIs over P-values. No formal sample size calculation was conducted because of the pilot nature of the study, and a sample size of 40 was selected to explore feasibility and preliminary efficacy. The study protocol was approved by the Ethics Committee of our Medical and research Center (IR.RHC.REC.1397.020) and registered in the Iranian Registry for Clinical Trials (IRCT) (registration No.: IRCT20200111046084N1). All participants provided informed consent before participating in the study and the study conformed to the provisions of the Declaration of Helsinki.

Between January 2022 and December 2023, 675 patients underwent diagnostic cardiac catheterization via radial artery access, of whom 54 (8%) developed RAO. Among these 54 patients, 10 did not participate in the study and 4 had other indications for anticoagulation therapy. After exclusion of these 14 patients, the remaining 40 patients were randomized into the rivaroxaban and enoxaparin groups with similar frequency.

Radial pulse was lost during the post-catheterization examination in all randomized patients, and 37 of 40 (92.5%) patients had a disturbed Allen test. Since patients requiring DAPT (e.g., patients with acute coronary syndrome) or receiving therapeutic anticoagulation were excluded from the study, no antiplatelet therapy was prescribed to our study population during the 28-day study period.

Three patients in the enoxaparin group withdrew consent and did not participate in follow-up. Finally, 37 patients (median age 55 [IQR: 48 to 64] years, 26 female patients [70.3%]) completed the 28-day ultrasound follow-up (Table 1).

Table 1 . Baseline characteristics of the study population.

	Rivaroxaban (n=20)	Enoxaparin (n=17)	P-value
Age (y)	54.5 (46.2-66.7)	56.0 (50.0-61.5)	0.73
Sex, female	17 (85.0)	9 (52.9)	0.03
Family history of coronary artery disease	3 (15.0)	2 (11.8)	0.77
Current smoker		1 (5.9)	0.45
Previous comorbidities
Diabetes mellitus	6 (30.0)	5 (29.4)	0.96
Hypertension	11 (55.0)	11 (64.7)	0.54
Dyslipidemia	9 (45.0)	6 (35.3)	0.54

Values are presented as number (%) or median (interquartile range)..

The imaging outcomes of the two study groups are summarized in Table 2. In 30 of 37 (81.1%) patients, RAO showed either partial resolution (29.7%) or complete resolution (51.4%). There was no statistically significant difference in resolution rates between the rivaroxaban and enoxaparin groups. No major or minor bleeding events occurred during the 28-day follow-up period.

Table 2 . Sonographic status of radial artery occlusion at 4-week follow-up.

Status	Rivaroxaban (n=20)	Enoxaparin (n=17)	Odds ratio (95% CI)
Complete or partial resolution	16 (80.0)	14 (82.3)	0.85 (0.16-4.50)
Complete resolution	9 (45.0)	10 (58.8)	0.57 (0.15-2.11)
Partial resolution	7 (35.0)	4 (23.5)	1.75 (0.41-7.45)
No change	4 (20.0)	3 (17.6)	1.16 (0.22-6.13)

Values are presented as number (%) or median (range)..

CI, confidence interval..

Although RAO is a relatively common post-radial catheterization complication, no high-quality evidence exists regarding the optimal antithrombotic regimen with an acceptable recanalization rate and minimal adverse bleeding events.

Available prospective studies that evaluated different antithrombotic regimens in RAO patients are summarized in Table 3. Reported recanalization rates range from 32% to 86.7%, with one study [21] indicating that untreated patients have limited spontaneous recanalization rates. However, considerable heterogeneity exists among these studies, with variations in dosages (prophylactic versus therapeutic) and anticoagulation medications (low-molecular-weight heparin (LMWH) [22,23], fondaparinux [24], direct oral anticoagulants (DOACs), and vitamin K antagonists [25]). Consequently, no definite conclusion can be drawn from the available evidence. In addition, the strategy for concomitant DAPT therapy is unclear in most trials. Although two RCTs were found in our systematic search, both had limited sample size and were thus underpowered. Furthermore, the future applicability of radial access in patients with partial versus complete recanalization remains unclear.

Table 3 . Major prospective studies on the efficacy and safety of different anticoagulation regimens in treating post-catheterization radial artery occlusion.

Author	Year	Design	Study population	Anticoagulation regimen	Imaging method	Key finding
Amirpour et al. [21]	2023	RCT	30 patients symptomatic RAO randomized into reduced-dose apixaban vs. conservative management	30-day apixaban 2.5 mg twice daily	Duplex ultrasound	86.7% vs. 53.3% recanalization in treated vs. untreated patients
Rammos et al. [22]	2018	Case-control study	8 patients with symptomatic RAO received therapeutic dose anticoagulation (NOAC/LMWH) vs. 11 patients with therapeutic dose anticoagulation (NOAC/LMWH) plus alprostadil vs. 11 patients left untreated	3-month body-weight-adjusted LMWH or rivaroxaban 15 mg twice daily for 21 days, then 20 mg daily or apixaban 5 mg twice daily for 5 days, then 5 mg daily	Doppler ultrasound	79.5% vs. 0% recanalization in treated vs. untreated patients No additional benefit of alprostadil
Didagelos et al. [23]	2022	RCT	58 patients symptomatic RAO randomized into therapeutic LMWH vs. conservative management	4-week body weight–adjusted LMWH	Doppler ultrasound	41.4% vs. 10.3% recanalization in treated vs. untreated patients Bleeding events in 13.8% patients treated with LMWH vs. 3.4% in controls
Zankl et al. [24]	2010	Prospective observational study	30 symptomatic RAO treated with parenteral anticoagulation vs. 21 untreated asymptomatic RAO	4-weeks prophylactic/therapeutic LMWH or fondaparinux. The anticoagulation dosage changed according to assigned antiplatelet regimen (SAPT vs. DAPT)	Doppler ultrasound	86.7% vs. 19.1% partial or complete recanalization in treated vs. untreated patients
Schlosser et al. [25]	2023	Prospective observational study	93 patients with new RAO received oral AC	Oral AC for at least 30 days AC selection according to the treating physician The majority received NOACs (66 out of 71: rivaroxaban n=51, apixaban n=11, edoxaban n=6, dabigatran n=1); 5 VKA	Duplex ultrasound	Reperfusion rate at 30 days was 13% in no oral AC and 32% oral AC The highest reperfusion rate was with VKA (80%)

RCT, randomized controlled clinical trial; RAO, radial artery occlusion; vs., versus; LMWH, low-molecular-weight heparin; SAPT, single antiplatelet therapy; DAPT, dual antiplatelet therapy; AC, anticoagulation; NOACs, non-vitamin K oral anticoagulants; VKA, vitamin K antagonist..

As noted, RAO is often an asymptomatic complication of cardiac catheterization that, if left untreated, can preclude the use of the radial artery for future procedures. The value of our pilot RCT was limited by its small sample size and the exclusion of patients with concomitant DAPT. In addition, the length of thrombosis on ultrasound examination before treatment assignment was not compared between the two study groups, which may have affected the results.

However, our analysis showed the potentially comparable efficacy of LMWH and DOACs for RAO resolution with no major bleeding events, which can be applied in future large-scale clinical trials.

Study medication was donated by Actover Co., without any role in the design and conduct of the study. The authors would like to thank Maryam Zarinsadaf, Sara Tayyebi, MS, Esmaeil Soomari, MS (Rajaie Cardiovascular, Medical and Research Center) for their support and contribution to the study.

This work was supported by Rajaie Cardiovascular Institute.

The authors have nothing to disclose.

Conception and design: MM, SSA, KRK, PR, PS. Data analysis and interpretation: FR, YMK, PS. Writing the article: MM, SSA, FR, YMK, PS. Critical revision of the article: MM, PS. Final approval of the article: all authors. Statistical analysis: FR, PS. Obtained funding: MM, PS. Overall responsibility: MM, PS.