European Heart Journal (2025) 46, 35–37 VIEWPOINT

https://doi.org/10.1093/eurheartj/ehae615 Thrombosis and antithrombotic treatment

Non-vitamin K oral anticoagulants in valvular

heart disease before surgery: a tale of bridging
vs. no bridging

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1 2 3
Raffaele De Caterina *, Hugo ten Cate , and Vittorio Pengo
1
Chair of Cardiology University of Pisa and Cardiovascular Division, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy; 2Cardiovascular Research Institute Maastricht, Maastricht
University, and Thrombosis Expertise Centre, Maastricht University Medical Centre, Maastricht, Netherlands; and 3Department of Cardio-Thoracic-Vascular Sciences and Public Health,
University of Padua, Padua, Italy

Received 30 March 2024; revised 19 July 2024; accepted 25 August 2024; online publish-ahead-of-print 8 October 2024

Graphical Abstract

Patients with atrial fibrillation on a non-vitamin K antagonist oral anticoagulant scheduled for
low- or high-bleeding-risk surgery (including bioprosthetic valve implantation or valve repair)

Very high thrombotic risk YES Consider bridging

(e.g., CHA2DS2VASc 7 or more) with a LMWH
NO

No bridging

No perioperative bridging with LMWH / UFH

Discontinuation time of the NOAC
Dabigatran Apixaban - Edoxaban - Rivaroxaban
Low risk High risk Low risk High risk
CrCl ≥80mL/min ≥ 24h ≥ 48h ≥ 24h ≥ 48h
CrCl 50–79mL/min ≥ 36h ≥ 72h ≥ 24h ≥ 48h
CrCl 30–49mL/min ≥ 48h ≥ 96h ≥ 24h ≥ 48h
CrCl 15–29mL/min Not indicated Not indicated ≥ 36h ≥ 48h
CrCl <15mL/min No official indication for use

A practical algorithm to decide on heparin bridging in patients with atrial fibrillation scheduled for high-risk surgery. CHA2DS2-VASc, congestive heart
failure, hypertension, age ≥ 75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74, forgoing the sex category; LMWH,
low-molecular-weight heparin; NOAC, non-vitamin K antagonist oral anticoagulant; CrCl, creatinine clearance; UFH, unfractionated heparin.

* Corresponding author. Tel: +39 050 996 751, Email: [email protected]

© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact [email protected] for
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36 Viewpoint

Patients needing anticoagulation because of atrial fibrillation or other phenprocoumon, should not this be an even more compelling argu­
thromboembolic conditions, but at one point also scheduled for sur­ ment with drugs the effect of which rapidly disappears after interrup­
gery, have to walk the tight rope between an excess risk of bleeding tion and rapidly reappears, with peak in plasma concentration and
connected to surgery in the presence of coagulation impairment due activity in the order of 1–2 h, after resumption? Indeed, the introduc­
to anticoagulation and the risk of thromboembolic events in case of tion of NOACs marked a further reinforcement of the message of
prolonged anticoagulant interruption. When vitamin K antagonists avoiding bridging as much as possible. After the PAUSE trial,7 the
(VKAs) were the only anticoagulants available, with an offset of action 2021 EHRA Guide8 also provided a decision-making table, whereby
of days, there has been a long tradition of bridging VKA interruption the time of discontinuation before surgery is calibrated according to
with shorter-acting parenteral heparins. (i) the type of NOAC (dabigatran plasma concentrations and activity
are more strongly related to renal function than the factor Xa inhibi­
tors rivaroxaban, apixaban, and edoxaban), (ii) renal function, and
The theory behind bridging

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(iii) the bleeding risk related to surgery. According to this scheme,
The rationale of heparin bridging is here to limit at maximum the time for a patient on a factor Xa inhibitor undergoing cardiac surgery
of missing protection from thromboembolism by substituting a long- (considered at a high risk for bleeding) and with a creatinine clearance
acting anticoagulant (∼5 days in the case of warfarin)1 with a short- > 50 mL/min, a discontinuation time of 48 h before surgery with no
acting drug, in most cases a subcutaneous low-molecular-weight bridging was recommended. This should be the case also for patients
heparin (LMWH; half-life in the order of 4–5 h for enoxaparin2). with atrial fibrillation and a bioprosthetic valve, who are suitable for
This would allow to keep the interval of absence of anticoagulation treatment with a NOAC.9
as short as possible, but also allowing adequate haemostasis at the
critical time of surgery.3
And now: is there any evidence
Challenging the dogma to change recommendations?
Bridging has been the paradigm for anticoagulation management until The latest ESC Guidelines on valvular heart disease,10 addressing the
the American College of Chest Physicians started to challenge it in their same issue for patients after prosthetic valve implantation or valve re­
2012 recommendations4 based on an overall analysis of previous trials. pair in the perioperative and postoperative periods, have more recently
The conclusion of the BRIDGE trial5 later confirmed such conclusions: (re)proposed (LMW) heparin bridging in four conditions, namely, pa­
contrary to the widely held belief that bridging with heparin was a way tients with a mechanical prosthetic heart valve, patients with significant
to decrease the risk of stroke in patients with atrial fibrillation, this mitral stenosis, patients with an acute thrombotic event within the pre­
head-to-head comparison of bridging vs. no bridging in patients on war­ vious 4 weeks, and also patients with ‘high acute thromboembolic risk’
farin undergoing surgery was clearly in favour of the no-bridging (patients with a CHA2DS2-VASc score > 3 for women or >2 for men).
strategy. BRIDGE was a randomized, double-blind, placebo-controlled While the first three settings are—in our opinion—acceptable for re­
trial in which, after perioperative interruption of warfarin, patients commending bridging, the recommendation in the last one is trouble­
were randomly assigned to receive bridging anticoagulation with the some, because it will imply the need for bridging in most patients with
LMWH dalteparin or matching placebo administered subcutaneously a bioprosthetic valve or valve repair and atrial fibrillation undergoing sur­
twice daily, from 3 days until 24 h before the procedure and then gery. Such a recommendation was also proposed as Class I (‘you MUST
for 5 to 10 days after it. Warfarin treatment was stopped 5 days before follow it’),10 although with a level of evidence C (Expert Consensus), out
the procedure and was resumed within 24 h after it. The incidence of of the setting of mechanical heart valves and moderate-to-severe mitral
arterial thromboembolism was 0.4% in the no-bridging group and 0.3% stenosis where VKAs have to be used. Unfortunately, and citing this
in the bridging group [risk difference, 0.1%; 95% confidence interval document, a comprehensive literature review referring to cardiac sur­
(CI) −0.6 to 0.8; P = .01 for non-inferiority]. The incidence of major gery patients using NOACs11 has reiterated such a recommendation,
bleeding was 1.3% in the no-bridging group and 3.2% in the bridging citing the primary 2021 ESC/EACTS Guideline document,10 and also
group (relative risk, 0.41; 95% CI 0.20–0.78; P = .005 for superiority). without explicitly restricting this recommendation to the context of
The study, however, had many limitations, with few patients having a valvular heart disease.
CHADS2 score of 5 or 6 (the mean score was 2.3) and only 29 of
1884 (1.5%) having mitral stenosis, and also using full therapeutic
dose of LMWH in all patients. Thus, notable concerns about this strat­ We believe such a shift and
egy remained in patients with mechanical heart valves, for whom evi­ apparent broadening of
dence of anticoagulant efficacy and safety of LMWH had in the
meantime been provided,6 or moderate-to-severe mitral stenosis recommendations for heparin
not well represented in the trial. bridging is at the same time
unwarranted and potentially
The introduction of non-vitamin K dangerous
antagonist oral anticoagulants The risk of bleeding connected with the simultaneous use of two antic­
All non-vitamin K antagonist oral anticoagulants (NOACs), entered oagulants (a NOAC and a LMWH) not susceptible to monitoring with
into practice between 2009 and 2012, are characterized by a the ‘standard’ coagulation tests is substantial, as shown by the BRIDGE
10–14 h half-life in conditions of normal renal function. If bridging has lit­ trial, with a more than doubling of the bleeding risk connected to
tle or no role with long-acting VKAs, such as warfarin, acenocoumarol, or LMWH bridging.5 This is rather intuitive considering the practical
Viewpoint 37

impossibility of having a test of haemostasis capturing the joint

haemostatic impairment of the two classes of anticoagulants here
Declarations
at stake. Conversely, the risk of a thromboembolic event in the im­ Disclosure of Interest
mediate (24 h) preoperative setting after NOAC discontinuation All authors declare no disclosure of interest for this contribution.
can be calculated, albeit with some approximation: for a patient
with a CHA2DS2-VASc score of 4, this is in the order of 9.3 stroke
or thromboembolic events/100 patient-years,12 meaning a probability References
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