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Minor surgical procedures and procedures where bleeding is easily controlled can be performed without VKA interruption. The INR should be monitored and maintained at the lower level of the therapeutic range. Major surgical procedures needing INR ≤1.5 require VKA interruption, and heparin bridging should be considered. However, the evidence to support bridging therapy is limited and derived from cohort studies with poor or no comparator groups.291 Furthermore, the current-generation mechanical prosthetic valves in the aortic position are associated with a lower risk of thromboembolism compared with the older ones.291 Randomized controlled trials of bridging vs. no bridging therapy for patients with AF who do not have an MHV have shown higher risk of bleeding without a change in incidence of thromboembolic events, and increasing concerns have been raised that bridging therapy exposes patients to higher bleeding risks without reducing the risk of thromboembolism.292,293 The recently published PERI-OP trial compared bridging therapy vs. placebo in patients with either an MHV, AF, or atrial flutter who required interruption of OAC therapy for surgery, and found no significant benefit for post-operative dalteparin bridging to prevent major thromboembolism.294 The results were consistent for the AF (n = 1166) and MHVs groups (n = 350). Therefore, in patients with MHVs with a low risk of thromboembolism (e.g. mechanical bileaflet aortic valve in patients with sinus rhythm), bridging may not be needed. In patients with MHVs with a high risk of thromboembolism (mechanical aortic valve replacement [AVR] and any thromboembolic risk factor, or an older-generation mechanical AVR, or a mechanical mitral or tricuspid valve replacement), bridging with heparin should be considered during the peri-operative time interval when the INR is subtherapeutic (Figure 8). In all situations, the risks of bleeding should be weighed against the benefits of thromboembolism prevention. Intravenous unfractionated heparin (UFH) is the only heparin treatment approved for bridging in patients with MHVs. Subcutaneous low molecular weight heparin (LMWH), although used off-label, has supplanted the use of UFH as a bridging therapy, owing to the lower incidence of thrombocytopenia, greater convenience, more predictable dose–response relationship, and significant cost saving resulting from outpatient administration. A meta-analysis of nine studies of 1042 patients with MHVs showed no differences between LMWH and UFH in the risks of thromboembolic events or major bleeding events.295 When LMWH is used, it should be given at a therapeutic dose twice a day and adjusted for renal impairment, when applicable. Anti-factor Xa (FXa) activity monitoring with target levels from 0.5–1.0 U/mL may be useful when the dosage may be difficult to determine (e.g. in patients with renal dysfunction or obesity). Vitamin K antagonist bridging strategies are shown in Supplementary data, Figure S2.

5.3.2.1.2 Vitamin K antagonists for atrial fibrillation/venous

thromboembolism. In patients using VKA for AF or venous thromboembolism (VTE), invasive procedures with a low bleeding risk can be performed without VKA interruption.296–299 The INR should be monitored and maintained at the lower level of the therapeutic range. When interruption is necessary due to high bleeding risk procedures, the BRIDGE trial in AF patients showed that 3–5 days of warfarin interruption without bridging was superior to heparin bridging, having the same incidence of arterial and venous thromboembolism and significantly lower incidence of major bleeding.292 Bridging therapy may be considered for patients with a high thrombotic risk (i.e. AF with CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65–74 years, sex category [female]) score .6, recent cardioembolic stroke ,3 months, or high risk of VTE recurrence, weighing the risk of bleeding against the risk of thromboembolism291,294,300 (see Supplementary data, Figure S3).

5.3.2.1.3 Restarting vitamin K antagonists after invasive proce-

dures or surgery. Patients who have interrupted VKA treatment before surgery should restart the OAC 12–24 h after the invasive procedure, if the bleeding is well-controlled and gastric and intestinal reabsorption have been re-established. The restarting dose should be the maintenance dose plus a boosting dose of 50% for 2 days. Patients managed with bridging therapy should start LMWH or UFH together with VKA 24 h after surgery, if the bleeding is wellcontrolled and maintained, until the INR has reached the therapeutic range. In patients undergoing surgery with a high bleeding risk, therapeutic dose LMWH should be delayed for 48–72 h after haemostasis has been secured.

5.3.2.1.4 Reversal of vitamin K antagonists. Reversal of VKA can

be managed with vitamin K, prothrombin complex concentrates (PPCs), and plasma administration. Vitamin K (from 2–10 mg depending on the INR value) can be used orally, with a predictable reduction in INR in 18–24 h or i.v. (in 25–50 mL normal saline over 15–30 min) for more rapid INR reduction (4–6 h). It should be noted that coagulation factors can still be below normal despite INR normalization, which means that bleeding risk might not yet be normalized. In patients needing reversal for immediate major surgery, PPCs or plasma should be used. Four-factor PPCs are the preferred option301 and are dosed on the basis of INR and body weight (INR 2–4 at 25 U/kg, INR 4–6 at 35 U/kg, INR .6 at 50 U/kg, with a maximum dose of 5000 U at 100 kg of body weight). When fourfactor PPCs are unavailable, three-factor PPCs or plasma may be used. Patients requiring a reversal agent need careful monitoring of haemostatic parameters and evaluation of thrombotic and bleeding risks in the peri-operative phase, as reversal might be insufficient or a prothrombotic rebound might occur. In the latter case, an interdisciplinary decision should be made with regard to early resumption of anticoagulation treatment.

5.3.2.2 Non-vitamin K antagonist oral anticoagulants

Four drugs are currently used: dabigatran (factor IIa inhibitor), apixaban, rivaroxaban, and edoxaban (FXa inhibitors). The pharmacokinetic and pharmacodynamic characteristics of these drugs are shown in Table 8.

5.3.2.2.1 Unplanned surgery in patients on non-vitamin K antag-

onist oral anticoagulants and reversal for emergency procedures. When an urgent surgical intervention is required, it is recommended that NOAC therapy is immediately interrupted. Peri-operative management of NOAC therapy in specific procedural settings and suggested strategies for potential reversal of NOAC anticoagulant effect are shown in Figures 9–1199,240,302 (see Supplementary data, Table S5). Downloaded from academic.oup.com/eurheartj/article/43/39/3826/6675076 by guest on 07 October 2026