Activated Clotting Time During Unfractionated Heparin-Supported Coronary Intervention

Is Access Site the New Piece of the Puzzle?

Corresponding Author

• Download figure
• Open in new tab
• Download powerpoint

• activated clotted time (ACT)
• clinical outcomes
• heparin, percutaneous coronary intervention (PCI)
• radial access

Percutaneous coronary intervention (PCI) has developed a pivotal role in the management of patients with stable or unstable coronary artery disease (CAD). The inhibition of the coagulation cascade, and platelet activation, adhesion, and aggregation are key steps to optimize the results of PCI and prevent periprocedural ischemic complications; however, the degree of antithrombotic effect should minimize bleeding risks. Unfractionated heparin (UFH) has the main advantages of being cheap and antagonizable by means of intravenous protamine sulfate, thus it remains the most widely used anticoagulant agent during PCI. However, UFH has a poorly predictable effect on the coagulation cascade and a relatively narrow therapeutic window (1,2). Consequently, the measurement of activated clotting time (ACT) at the time of PCI has been advocated to mitigate both ischemic and bleeding events during or soon after intervention. The use of ACT was initially recommended in the mid-1970s to guide administration and reversal of UFH during cardiopulmonary bypass, then the diffusion of these interventions led to the development of automated ACT measurements (3). In 1990s, with the advances in the field of interventional cardiology, more and more cardiologists proposed to use in-laboratory bedside coagulation monitoring to assess heparin requirements during interventional procedures (3). Throughout the years, ACT monitoring to adjust UFH dosing during PCI has been promoted as the standard practice, although many centers, especially in Europe, do not assess it routinely. An intravenous UFH bolus of 70 to 100 U/kg is recommended to achieve a target ACT of 250 to 300 s (Hemotech device) or 300 to 350 (Hemochron device) without planned use of glycoprotein IIb/IIIa inhibitors (GPI) or 50 to 70 U/kg bolus to achieve an ACT of 200 to 250 s when the concomitant use of GPI is anticipated. Interestingly, no study has prospectively assessed the value of ACT-guided UFH administration as compared with standard UFH dosing, and all recommendations concerning optimal ACT values are based on retrospective and relatively underpowered registry data. What further complicates the interpretation of available data is that conflicting data have been reported on the association of ACT with ischemic or bleeding complications (Table 1) (4–14).

To date, a large body of evidence supports the use of transradial (TR) approach over transfemoral (TF) for PCI, particularly in acute coronary syndrome (ACS) patients, due to the lower risk of access-site–related bleeding complications and decreased mortality risk (15). However, there is limited evidence on whether the ACT target to avoid ischemic and bleeding complications should vary based on the selected access site. Interestingly, the lack of association between high ACT values and bleeding outcomes in some recent studies may be justified by the frequent use of radial access site for coronary angiography and intervention (7,9).

In this issue of JACC: Cardiovascular Interventions, Louis et al. (16) present the results of a large, 2-center, retrospective observational study exploring the role of ACT in patients undergoing PCI and receiving UFH alone. Overall, unadjusted and adjusted analyses showed that maximal ACT was associated with higher rates of major bleeding after TF (ACT value >290 s), but not TR PCI, whereas there was no clear association with the in-hospital ischemic risk, irrespective of the vascular access site. This finding may suggest that during TR-PCI, a more intense anticoagulation might be tolerated compared with TF-PCI as a result of a much lower access site bleeding risk in the former over the latter group of patients. This study comes from data collected in 2 American centers on 9,169 patients (mean age 66 years) who underwent PCI without GPI. Two-thirds of the patients were male, roughly 85% presented with ACS, and the majority of them received a single-vessel PCI. Only 13% of patients received new P2Y₁₂ inhibitors, however.

Some important points of this study should be considered.

• 1. ACT values were missing in 10.5% of patients initially screened (1,532 of 14,634).

• 2. The ACT value at peak is analyzed as a standalone parameter, irrespective of relevant factors relating to UFH management (use of pre-PCI bolus and infusion of UFH, dose and number of intraprocedural UFH boluses, additional use of UFH doses guided by prior ACT values, patient body weight, and duration of the procedure).

• 3. The definition of bleeding occurrences is not standardized (i.e., BARC [Bleeding Academic Research Consortium], TIMI [Thrombolysis In Myocardial Infarction], or GUSTO [Global Use of Strategies to Open Occluded Arteries]), and bleeding events were not independently adjudicated. Moreover, the definition of periprocedural or non–procedural-related myocardial infarction is missing.

• 4. TR and TF cohorts were imbalanced (the TR group comprised roughly one-third of the overall population), and the TR cohort experienced a lower rate of overall bleeding complications, which were entirely driven by a lower rate of access site events. As a result, the lower statistical power to assess an association between ACT and bleeding in the TR group might explain the null finding in this group of patients. Moreover, in the TF group, the majority of bleeding events were access-related. The bottom line is that this analysis is largely underpowered to assess a possible association between non-access site bleeding and peak ACT values.

• 5. Hemochron device was used in all patients, thus, although this is the most widely used device, these findings should not be extended to other devices.

These findings, therefore, should be interpreted with caution and should not support the misleading conclusion that radialist operators can dose or overdose UFH liberally.

Non–access site bleeding, especially in the context of prospective randomized studies comparing TR versus TF intervention in ACS patients (7,15), is not so rare, is not influenced by the selection of the access site, and more closely correlates with mortality outcomes (17,18). On the other hand, this observation does reinforce the role of radial artery in current practice and adds to the growing body of evidence that both technical and pharmacological aspects should be regarded as highly interconnected: It is only then when the puzzle comes together!

• 2018 American College of Cardiology Foundation