Bivalirudin and Transradial Access – The End of the Bleeding Era for Catheterization Procedures?

The most common complications of catheterization procedures are access-site bleeding and hematoma which occur in 2–10% of all procedures.¹ Even after multivariable adjustment, numerous studies have shown periprocedural bleeding to be an independent predictor of morbidity and mortality.² Bleeding endpoints used in most clinical trials combine both access site and internal organ-related bleeding. The importance of access-site bleeding was demonstrated by Doyle et al in over 17,000 patients.³ Femoral bleeding or large hematomas requiring blood transfusions and retroperitoneal hemorrhage were associated with a 10-fold, 12-fold and 44-fold increased risk of death at 1 month, respectively, and a longer post-procedural stay. Transradial access (TRA) for percutaneous coronary interventions (PCI) has gained increasing popularity after the pioneering efforts of Campeau and Kiemeneij.^4,5 TRA is associated with up to 50–70% reduced access-site bleeding as compared to transfemoral access (TFA).^6,7 Another meta-analysis showed an absolute risk reduction of 1.8% for major bleeding with TRA with a number needed to treat of 56 patients to prevent one major bleeding event.⁸ Prevention of bleeding with TRA should be compounded to the lower cost, nursing workload, length of stay and increased patient satisfaction.⁹ In light of the above, TRA has been advocated as the access of choice for all coronary interventions.¹⁰ It is however astonishing that TRA accounts for 7,11 This could be partially due to the technically more challenging procedure, steeper learning curve and higher radiation exposure. However, among experienced operators there is no difference in procedural success rates and duration.¹² Use of bivalirudin as monotherapy has been shown to have a significantly lower risk of bleeding compared to the combination of unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors with non-inferior ischemic outcomes.^13,14 Therefore, it can be hypothesized that the combination of bivalirudin and TRA would result in a significantly reduced bleeding risk. In a subgroup analysis of the ACUITY trial, use of bivalirudin was associated with significantly lower access-site bleeding with TFA, but not with TRA. However, non-access-site organ bleeding was reduced to a similar extent in both TFA (4.1% vs 7.4%; p 15 This is of exceptional significance as non-access-site bleeding can account for a significant proportion of all bleeds, especially in patients treated for acute coronary syndromes.⁹ Bivalirudin is the preferred anticoagulant for TRA PCI in the United States.¹¹ Bivalirudin, however, is expensive and not labeled for use in diagnostic catheterization. Therefore, patients undergoing ad-hoc TRA PCI usually receive UFH for the diagnostic part of the procedure and are then transitioned to bivalirudin. In this issue of the Journal, Singh and colleagues help address this vital issue.¹⁶ In a single-center retrospective observational study, stable patients undergoing non-urgent PCI were anticoagulated with a 2,500 U bolus of UFH at the beginning of the procedure, followed by bivalirudin (0.75 mg/kg bolus and 1.75 mg/kg/hr infusion) only if PCI was carried out. Outcome measures included bleeding and radial artery occlusion (symptom-led and ultrasound-confirmed). There were no major bleeding events, 6 cases of minimal bleeds and only a single case of radial artery occlusion. Radial artery occlusion (RAO) is a specific complication of TRA that can be prevented with the administration of UFH at a dose of 50 U/Kg and the use of “patent hemostasis.”^17,18 Because of the dual blood supply to the hand via the radial and ulnar arteries, the great majority of RAO cases are clinically silent, but preclude the use of the radial artery for future catheterization procedures. The low rate of RAO reported by Singh et al is possibly the result of ascertainment bias, due to the lack of systematic assessment of radial artery patency at short and long term.¹⁶ In addition, this study further confirms the findings of a smaller pilot study that used low doses (1,000–2,500U) of UFH with ad-hoc bivalirudin.¹⁹ Similarly, other observational studies have also demonstrated the safety of bivalirudin in preventing RAO.²⁰ Figure 1 displays a proposed algorithm for transitioning from UFH to bivalirudin in ad-hoc PCI after diagnostic catheterization. The need for GP IIb/IIIa inhibitors and prolonged (2-hour) bivalirudin infusion can be individualized according to the patient’s risk and the thrombotic burden of the target lesion.²¹ It is now well established that TRA significantly decreases access-site bleeding in comparison with transfemoral access. TRA combined with low-dose UFH and ad-hoc bivalirudin promises to also decrease major organ bleeding without increased RAO rates, and at the same time, does not seem to compromise procedural success. Future randomized, controlled trials need to investigate the viability and economics of bivalirudin for diagnostic transradial procedures and possibly eliminate the ambiguity of UFH dosing post sheath insertion. The increased safety of TRA compounded with the more predictable pharmacokinetics and decreased bleeding rates associated with bivalirudin could mean the end of the bleeding era of cardiac catheterization and interventions. With the increased interest in transradial catheterization in the United States, safer catheterization procedures appear to be a tangible goal to be attained within the next few years. Once the radial artery becomes the preferred and most frequently used access site for catheterization procedures, clinician will be able to determine the optimal antithrombotic strategy based on the individual risk for ischemia versus bleeding complications, most of which will be non-access-related.

References

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———————————————————— From the Cardiovascular Division, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. Disclosures: Dr. Cohen has received consulting honoraria from Medtronic and speakers bureau honoraria from Medtronic and Terumo Medical. Dr. Badheka reports no conflicts of interest regarding the content herein. Address for correspondence: Mauricio G. Cohen, MD, FACC, Cardiovascular Division, University of Miami Miller School of Medicine, 1400 N.W. 12th Avenue, Suite 1179, Miami, FL 33136. E-mail: mgcohen@med.miami.edu