Temporary Discontinuation and Restarting of Oral Anticoagulants for Neurological and Cardiac Indications

Background: Approximately 1 million people in Germany are under treatment with an oral anticoagulant (OAC) for the primary or secondary prophylaxis of arterial and venous thromboembolic disease. Each year, 12–20% of them undergo an invasive procedure or operation. The temporary discontinuation and restarting of OAC for comorbid conditions, complications, and invasive procedures should be designed both to reduce thromboembolic events and to avoid hemorrhagic complications.

Methods: In this narrative review, we present the state of the evidence and the current guideline recommendations, particularly for cardiological and neurological/neurosurgical indications.

Results: In periprocedural discontinuation of OAC, the risk of hemorrhage is higher if unnecessary heparin bridging is performed, or if the chosen pausing interval is too short. On the other hand, the thromboembolic risk is higher while the patient is not taking OAC. In the case of invasive procedures or complications under OAC, the individual hemorrhagic and thromboembolic risks should be assessed, and the timing of discontinuation and reintroduction of the OAC should be decided upon in view of the potential clinical consequences. Prior thromboembolic events and hemorrhages should be taken into account, as well as the patient’s age, kidney function, accompanying illnesses, and any co-medication with antiplatelet agents. For ischemic stroke, recent studies indicate that the early (re-)introduction of OAC is advantageous. Whether and when patients who have sustained an intracranial hemorrhage should be given OAC remains unclear and is a current topic of investigation.

Conclusion: A standardized approach to the periprocedural administration of OAC and the management of complications should be agreed upon by interdisciplinary consensus in each clinical institution.

Cite this as:
Kellert L, Sinner MF, Höllig A, Nolte CH, Linnemann B: Temporary discontinuation and restarting of oral anticoagulants for neurological and cardiac indications. Dtsch Arztebl Int 2026; 123: 198–206. DOI: 10.3238/arztebl.m2025.0211

Approximately 1 million people in Germany are now taking anticoagulants for the primary or secondary prevention of thromboembolic events. Common indications for oral anticoagulation (OAC) are atrial fibrillation (AF), venous thromboembolism (VTE), and mechanical heart valve replacement (MHVR).

Direct oral anticoagulants (DOACs) are mainly used for anticoagulation in patients with AF and VTE, as they are superior to traditional anticoagulants with regard to their lower risk of bleeding, favorable pharmacokinetics (rapid onset of action, short half-life), and fixed dosing (1, 2).

In contrast to DOACs, vitamin K antagonists (VKAs) exert their anticoagulant effect by inhibiting the synthesis of the vitamin K-dependent coagulation factors II, VII, IX, and X. This explains their delayed onset of action and prolonged effect. Further disadvantages include stronger interactions of VKAs with concurrent medications and food items, as well as the need for individualized dosing with regular monitoring of the INR. Nonetheless, VKAs are still given to patients at especially high thromboembolic risk, e.g., those who have had an MHVR or suffer from antiphospholipid syndrome (3).

Each year, 12–20% of anticoagulated patients undergo an invasive procedure or operation (4–6). The short-term interruption of DOACs usually suffices, but the periprocedural management of patients under treatment with VKA is more complex. The periprocedural hemorrhagic risk must be weighed against the thromboembolic risk in each case. If OAC must be discontinued, the interval without sufficient anticoagulation for the original indication should be held as short as possible. The half-life (HL) of the anticoagulant is determinative: if the treatment is interrupted for the duration of 2–3 half-lives, a 12–25% residual effect can be expected; after 5–6 half-lives, the residual effect is less than 5%.

Learning objectives

This article is intended to help readers to:

• know the key general principles for pausing and resuming oral anticoagulation, including individualized risk stratification;
• understand the specific considerations in cardiological conditions including atrial fibrillation, status post heart valve replacement, and left ventricular thrombus;
• be aware of the established decision-making tools regarding the indication for oral anticoagulation in neurological and neurosurgical situations, including after ischemic stroke and after spontaneous or traumatic intracerebral hemorrhage.

Methods

The current state of the evidence and the guideline recommendations for cardiological and neurological/neurosurgical scenarios are presented in the form of a focused narrative review based on national and international guidelines, clinical trials, and meta-analyses.

Periprocedural management of DOAC

For risk stratification, procedures are categorized as having a high, low, or very low risk of bleeding (Table 1). Patient-related risk factors such as age, drugs taken concurrently (e.g., antiplatelet drugs), kidney and liver failure, anemia, and a history of bleeding must be considered as well.

Table 1

Stratification of procedure-related bleeding risk and periprocedural DOAC management

As DOACs have short half-lives (Table 2), they need not be discontinued any earlier than 24 hours before procedures with a low risk of bleeding, and they can generally be restarted no later than 24 hours after the procedure in the absence of a hemorrhagic complication (Table 1). Dabigatran in particular must be paused for a longer time in patients with renal failure, as 80% of its elimination is via the kidneys (Table 3). Direct factor Xa inhibitors are eliminated renally to a lesser extent but should also be paused for longer times in patients with severe renal failure.

Table 2

Oral anticoagulant drugs: dosage, elimination, and antagonism

Table 3

Intervals for pausing DOAC treatment before planned invasive procedures, depending on the periprocedural bleeding risk and renal function (modified from Steffel et al. 2021) (37)

For procedures carrying a very low risk of bleeding, e.g., catheter ablation for AF, minor dental procedures, superficial dermatological procedures, or uncomplicated pacemaker or defibrillator implantation, the continuation of DOAC without any change is an alternative supported by recent studies; if this is done, the procedure should be performed at the trough concentration if possible (3, 7). For some patients, it may be advisable to skip the morning dose of a twice-daily regimen (apixaban, dabigatran) or to take the last dose of a once-daily regimen (edoxaban, rivaroxaban) on the evening before the procedure.

Before any procedure with a high risk of bleeding, DOAC should be paused for at least 48 hours; longer intervals are recommended for dabigatran and in patients with impaired renal function (Table 3). DOAC should be restarted no earlier than 48 hours after the procedure.

The routine determination of plasma levels before elective procedures is not recommended. In the PAUSE study, DOAC plasma levels were <50 ng/mL after a 48– to 72-hour interruption in 99% of cases, which implies no more than a minimal, clinically irrelevant residual effect (4, 8). Nonetheless, in cases with high bleeding risk or unclear pharmacokinetics (e.g., in renal or hepatic insufficiency), it may be advisable to check the plasma level before the procedure.

Heparin bridging is generally not required while DOAC are interrupted, as both the loss of effect on discontinuation of the drug and its return on resumption are rapid because of the short half-life (4). It may be advisable to give heparin postoperatively instead of restarting DOAC at once if enteric absorption is expected to be impaired (e.g., after major abdominal surgery, postoperative gastroparesis, or subileus), or if another intervention or operation may become necessary a short time after the initial one. If the risk of bleeding is high or the clinical course is complicated, In cases of prolonged high bleeding risk or complicated courses, low-molecular-weight or unfractionated heparin (LMWH, UFH) may be advantageous because of their shorter half-life, easier management, and flexible dosing. In patients whose OAC must be paused for longer times while they are immobilized, the indication for pharmacological VTE prophylaxis should be assessed.

The periprocedural management of VKA treatment

Heparin bridging during VKA treatment is associated with a 3.6-fold increased risk of severe bleeding (4.2% versus 0.9%; [95% confidence interval: 1.5; 8.5]) and does not lower the rate of thromboembolism during the interruption (9, 10). It should be remarked, however, patients with a high risk of thromboembolism were underrepresented in the relevant studies. For patients taking VKA to treat AF, bridging is generally not required even if their thromboembolic risk is considered to be high (more than 5% per year) (10). In contrast, individualized risk assessment is necessary in patients who have had a recent thromboembolic event or a mechanical heart valve replacement (11).

The periprocedural management of patients taking VKA is mainly guided by the risk of bleeding (Table 1). The periprocedural management of patients taking VKA is mainly guided by the risk of bleeding (Table 4) or VKA must be paused for a longer time, in which case the dosage—therapeutic, semi-therapeutic, or prophylactic—and duration of heparin bridging must be decided upon (12). Early, case-by-case interdisciplinary consultation is recommended. Elective procedures should not be performed within the first three months after a thromboembolic event, as the risk of recurrence is high.

Table 4

Stratification of thromboembolic risk (modified from Douketis et al. 2022) (12)

In Germany, phenprocoumon is the preferred VKA, but its periprocedural management has been little studied (13). When phenprocoumon is paused, the INR is expected to drop below the target range for at least two to three weeks, as its half-life (96–150 h) is longer than that of warfarin (36–42 h). Thus, especially after MHVR, anticoagulation should be bridged with low-molecular-weight or unfractionated heparin, at least when the VKA being paused is phenprocoumon. As the current guidelines for atrial fibrillation and venous thromboembolism favor anticoagulation with DOAC, rather than VKA, any periprocedural interruption provides an opportunity to review the indication for vitamin K antagonists and switch to a DOAC postprocedurally when indicated.

Phenprocoumon is discontinued approximately seven to ten days before a procedure, and warfarin about five days beforehand; longer periods may be necessary for older patients, those with a higher target INR range, or those taking a very low weekly dose (12). The INR should be checked immediately before the procedure; most procedures can be performed if the INR is below 1.5. Vitamin K should not be routinely given to accelerate the normalization of clotting function, as this can slow the return of the therapeutic effect when VKA are reintroduced (12). In the absence of bleeding complications, VKA can be restarted one day after the procedure at the usual maintenance dose. Heparin bridging, if carried out, is discontinued only after the INR value has returned to the target range.

Special cardiological situations

Many cardiac conditions call for long-term, sometimes permanent OAC, to be interrupted only for procedures or in cases of very high bleeding risk. For some patients, planned discontinuation or a longer pause is possible in consideration of the individual risk profile.

Atrial fibrillation

OAC is often started as soon as AF is diagnosed. If a guideline-based evaluation reveals a very low thromboembolic risk (CHA₂DS₂-VASC score = 0), OAC provides no benefit (1) and should be discontinued unless there is another indication for it besides AF. Antiplatelet therapy instead of OAC is indicated only in patients with manifest atherosclerosis (e.g., coronary artery disease, cerebrovascular or peripheral arterial occlusive disease). It should be noted that vascular diseases add 1 point to the CHA₂DS₂-VASC score, potentially resulting in an indication for OAC. Moreover, additional comorbidities can increase the risk of thromboembolism over time, so the indication for resuming OAC should be reviewed at regular intervals (1).

In addition to OAC, symptom control of AF is important. Early rhythm control with restoration of sinus rhythm leads to better clinical outcomes than long-term rate control (14). Direct-current (DC) cardioversion and interventional ablation therapy are now common treatments for atrial fibrillation that play a major role in modern strategies for rhythm control. Cardioversion temporarily “stuns” the atria; ablation therapy (with any of the available energy sources) produces an endothelial lesion in the left atrium. Both temporarily elevate the risk of thromboembolism, and therefore, whatever the CHA₂DS₂-VASC score, adequate anticoagulation is required for at least three weeks before the procedure (1); if this is not done, transesophageal echocardiography is recommended to rule out intracardiac thrombi (1). Postprocedurally, anticoagulation is continued for at least four weeks after electrical cardioversion and for at least two months after ablation therapy and is then discontinued, as long as the CHA₂DS₂-VASC score still indicates a low risk of thromboembolism (1).

The pouch-like left atrial appendage (LAA) is a common source of thromboembolism, especially in the setting of atrial fibrillation with reduced blood flow velocity. Anticoagulants lower the risk of thromboembolism while also increasing the risk of bleeding, especially with long-term use. The risk of thromboembolism can be lowered alternatively with a catheter-delivered occlusion system (LAA occluder), but anticoagulation is more effective (1). In the absence of evidence of a net benefit to date, LAA occlusion is primarily reserved for patients with relevant contraindications to long-term OAC (1). Periprocedural antithrombotic therapy must be continued until the LAA occluder is endothelialized or significant residual flow in the LAA can be ruled out, in order to minimize the risk of device-associated thromboembolism (1, 2). For want of reliable data, there is currently no consensus on the optimal periprocedural antithrombotic therapy, so the decision must be made individually by each patient’s treatment team. After successful LAA closure, OAC are generally no longer indicated, and the further treatment is with acetylsalicylic acid (ASA).

Heart valve replacement

OAC can be paused or stopped in individual cases even after heart valve replacement. Interventional aortic valve replacement is rapidly evolving, and decisions about antithrombotic therapy should be made by the specialized implanting teams. After surgical MHVR, long-term anticoagulation with VKA is needed because of the thrombogenicity of the implanted foreign material (15). After surgical heart valve reconstruction or the implantation of a biological heart valve, VKA are given for a limited period of approximately three months after the procedure and then discontinued, unless there is another indication for OAC (15). OAC is usually not required after transcatheter aortic valve implantation (TAVI), because of the larger valve orifice area, higher blood flow velocity, and lower thrombogenicity of the foreign material constituting the artificial valve (15). Regular reevaluation of the indications for OAC is indicated so that any new indication can be recognized in a timely manner.

Left ventricular thrombus

Left ventricular thrombi can develop after myocardial infarction because of locally reduced blood flow velocity and a thrombogenically activated endothelium. Current guidelines recommend anticoagulation with VKA or DOAC for three to six months, with the aim of preventing appositional thrombus growth and promoting thrombus resolution via the body’s own fibrinolysis. OAC can often be stopped once the thrombus is no longer present (16).

Special neurological and neurosurgical situations

Ischemic stroke

10–15% of patients with an acute ischemic stroke receive oral anticoagulation (17). In the context of acute stroke, OAC is often paused at first to lower the risk of hemorrhagic transformation of the infarct. Restarting oral anticoagulation as early as possible is intended to lessen the risk of recurrent stroke, but it also increases the risk of bleeding. In the oral anticoagulant approval studies, an acute stroke in the preceding 7–14 days was an exclusion criterion for study participation. In the absence of study data, the pragmatic “1–3–6–12 rule” was applied, in which the start of OAC depends on the size of the stroke: from day 1 after a TIA, from day 3 after a minor stroke, from day 6 after a moderate stroke, and from day 12 after a severe stroke.

The potential benefit of earlier initiation of OAC has been studied in four large-scale clinical trials. In the TIMING trial, 888 patients with acute ischemic stroke (<72 h) and VHF were randomly allocated (1:1) to the early (<4 days) or late (5–10 days) initiation of OAC (18). The composite endpoint (stroke, intracerebral hemorrhage, death) was reached within 90 days by 31 (6.9%) patients in the early group and 38 (8.7%) in the late group. No symptomatic intracerebral hemorrhages (ICH) occurred.

The ELAN trial categorized patients on the basis of cerebral imaging into groups with minor, moderate, and severe stroke, and early OAC initiation was defined as being within 48 h for minor and moderate stroke and within 6–7 days for severe stroke (19). A late start was defined as the initiation of OAC after 3–4 days for small stroke, 6–7 days for moderate stroke, and 12–14 days for severe stroke. No difference between groups was found in the primary endpoint, although numerically fewer events were recorded after early OAC initiation (2.9% versus 4.1%). Severe ICH occurred in 2 patients (0.2%) within 30 days in each group. The largest trial on this topic is the OPTIMAS trial, which compared early (≤4 days) and late (7–14 days) OAC initiation after stroke in 3648 patients (20). The composite endpoint (ischemic stroke, ICB, and systemic embolism) was reached within three months by 59 (3.3%) patients in the early group and 59 (3.3%) in the late group. Symptomatic ICH occurred in 11 (0.6%) versus 12 (0.7%) patients. In the recently published START trial, patients who had sustained an ischemic stroke were divided into four groups and started on DOACs at different times (21); earlier initiation of DOACs after a stroke was found to be beneficial.

A meta-analysis of these four trials revealed a benefit for the early initiation of DOAC (≤4 days) with regard to the composite endpoint (ischemic stroke, symptomatic ICH, or unclassified stroke <30 days) (2.1% versus 3.0%, OR = 0.70; [0.50; 0.98], p = 0.039) (22). The stroke rate was lowered by earlier initiation (1.7% versus 2.6%, OR = 0.66, [0.45; 0.96], p = 0.029), without an increase in the rate of symptomatic IC (H0.4% vs. 0.4%, OR = 1.02, [0.43; 2.46], p = 0.96). These data support the early initiation of DOAC therapy after ischemic stroke in patients with AF. From a pragmatic standpoint,

• mild and moderate strokes should be treated with anticoagulation after 4 days and
• severe strokes after 6–7 days,

with due consideration given to infarct volume, location, and hemorrhagic transformation.

Intracerebral hemorrhage

The annual rate of cerebral hemorrhage among patients being treated with DOAC is approximately 0.5%, or 10 times higher than in persons not taking DOAC, and 24–67 % die as a result. Only a small percentage of the survivors regain good functional independence (23, 24). Approximately 25% of all spontaneous cerebral hemorrhages occur in association with OAC.

Patients who sustain an ICH and have an indication for OAC face a dilemma: the risk of a future stroke must be weighed against the risk of a recurrent ICH (Figure). Registry data suggest that resuming anticoagulation after an OAC-associated ICH lowers both the ischemic stroke risk and mortality (25, 26). Optimized blood pressure control is required.

Figure

Nonetheless, small-scale randomized trials have not shown any benefit of OAC. In the APACHE-AF trial, the combined vascular endpoint was equally frequent in the two groups (OAC / no OAC) (26% versus 24%, hazard ratio [HR] 1.05, not significant) (27). In the SoStart trial, ICH recurrence was insignificantly more common in the OAC group (8% versus 4%, adjusted HR = 2.42 ([0.72; 8.09]; p = 0.152) (28).

Likewise, no benefit was found for OAC after ICH in a meta-analysis involving 412 patients in which the primary endpoint was any stroke or cardiovascular death. The anticoagulated patients had fewer ischemic strokes (4% versus 16%) but more recurrent ICHs (6% versus 3%) (29). In the recently published PRESTIGE-AF trial (n = 319), OAC lowered the stroke rate from 8.6% to 0.8% over a median follow-up period of 1.4 years (HR = 0.05, [0.01; 0.36]); log-rank p < 0.0001, number needed to treat (NNT) 13; coprimary endpoints, first ischemic stroke and first recurrent ICH) but also led to significantly more hemorrhages (5% versus 0.8%, number needed to harm [NNH] (24), which limited its potential benefit (22). The ENRICH-AF trial of edoxaban versus no OAC, involving patients recruited from around the world, is not yet complete; results are expected in 2027 at the earliest.

The state of the evidence remains unsatisfactory. Interventional LAA occlusion may be an alternative. As approximately 90% of cardiac thrombi in AF arise in the LAA, occlusion might markedly lower the risk of thromboembolism (30). In multiple clinical trials, LAA occlusion has been found to yield similar or even superior benefit compared to OAC. The efficacy of LAA occlusion for various indications is now being tested in clinical trials, including in patients who have undergone CABG (ASAP TOO/StrokeCLOSE, CLEARANCE, COMPARE LAAO, Closure AF) .

It is recommended in cardiological guidelines that LAA occlusion should be considered for patients with AF who meet the indications for OAC but also have a high risk of bleeding (1). Matters to be considered include the device-related risk of thromboembolism and the current absence of consensus on short- or long-term antithrombotic therapy after LAA occlusion. Such decisions must be made on an individual basis by the specialized treatment team.

Hemorrhage due to trauma

There are insufficient data on the resumption of DOAC therapy after traumatic intracranial hemorrhage. As the pattern of injury in traumatic brain injury (TBI) is commonly mixed, no general recommendation can be given. There are also too few patients in the overall available evidence base for any clear recommendation to be given about anticoagulation after TBI. As with other types of intracranial hemorrhage, there is a tendency to resume OAC therapy early, although the optimal timing of resumption must be decided upon on a case-by-case basis. Results from the Restart tlCrH trial (NCT04229758), which concerns the optimal timing of DOAC reintroduction after traumatic intracranial hemorrhage in patients taking DOAC, are expected no earlier than 2027.

Chronic subdural hematoma (cSDH) is a common clinical condition, particularly in the elderly, whose incidence is rising—likely because of the aging of the population (31); patients in this age group commonly take antiplatelet and anticoagulant drugs because of their comorbidities. There have been studies on the role of antiplatelet drugs in this situation, but the evidence on anticoagulation in patients with cSDH remains limited. Traditionally, OAC was paused for an extended period after cSDH surgery, and sometimes also upon the diagnosis of a cSDH and during initial conservative management. The resumption of OAC within six weeks, or two weeks after its discontinuation for surgical treatment of cSDH, seems to offer a better cost-benefit profile with regard to hemorrhagic complications or cSDH recurrences in the VHF cohorts that have been investigated to date (32, 33). All of these studies, however, are post-hoc analyses of a subgroup from a randomized controlled trial or retrospective data collections. As an alternative to conventional surgical decompression, catheter-based embolization of the middle meningeal artery can now be performed to prevent recurrent cSDH, particularly in patients with multiple comorbidities and those who need to be anticoagulated (34), but this procedure has not yet been incorporated into all of the relevant international guidelines because there is as yet too little evidence supporting its efficacy.

As for the management of anticoagulant therapy in patients with other kinds of cerebrovascular disease, the evidence is sometimes no more than anecdotal. A small retrospective cohort study did not reveal any increased risk of rupture in anticoagulated patients with cerebral aneurysms, but too few patients were included to allow any generalized conclusion (35). There are no valid data demonstrating an increased risk of rupture under anticoagulation for cerebral aneurysms, cavernomas, or arteriovenous malformations; nonetheless, because of the paucity of the available data, decisions must be made case by case, with individual risk assessment. Antiplatelet drugs seem to lower the risk of bleeding in cavernomas (36).

Acknowledgment

We thank Prof. Martin Wiesmann, MD, Department of the Diagnostic and Interventional Neuroradiology at the University Hospital RWTH Aachen, for kindly providing the CT images in the Figure.

Conflict of interest statement
BL has received lecture honoraria from Bayer Vital, BMS/Pfizer, Boehringer, and Dalichi-Sankyo. LK has served as a paid consultant for, and/or received lecture honoraria and reimbursement of travel expenses from, the following companies: Alexion, AstraZeneca, Bayer Vital, Boehringer Ingelheim, and Bristol-Myers Squibb.

CN has received lecture honoraria from, and has served as a paid consultant and advisory board member for, the following companies: Alexion, AstraZeneca, Bayer, BMS, Novartis, and Pfizer. He receives royalties as a co-author from Springer Verlag.

The remaining authors declare that they have no conflict of interest.

Manuscript received on on 25 May 2025, revised version accepted on 10 November 2025.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Lars Kellert

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