Anticoagulation management of post-cardiac surgery new-onset atrial fibrillation

Short-term complications

In multiple series, new-onset PCSAF had been associated with increased in-hospital postoperative stroke and increased mortality.^3,6,11 These findings were similar in both on-pump (with cardiopulmonary bypass)³ and off-pump (without cardiopulmonary bypass) CABG surgery, and with and without valve surgery.¹¹

On the other hand, other single-center studies failed to find an association between new-onset PCSAF and increased risk of in-hospital stroke.^12,13 In one study, more than half of strokes occurred postoperatively rather than intraoperatively, and new-onset PCSAF was not associated with increased risk of stroke.¹³ However, older age and variables indicative of arteriosclerotic burden were risk factors for both intraoperative and postoperative stroke.¹³

Long-term complications

In most reports, new-onset PCSAF has been associated with worse long-term survival and increased thromboembolic complications.^6,14–16 For instance, in the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization trial of patients with left main coronary artery disease who underwent revascularization with either CABG or percutaneous coronary intervention, new-onset atrial fibrillation was an independent stroke predictor at three years in CABG patients.¹⁵

In another cohort study of patients who had undergone CABG surgery, risk of thromboembolism was lower in the PCSAF group than in the group with atrial fibrillation that was not valvular.¹⁴ Anticoagulation was associated with a lower risk of thromboembolic events in both groups, and thromboembolism was not significantly higher in patients with new-onset PCSAF compared with those who did not develop new-onset atrial fibrillation after surgery.

Risk of recurrence

There is considerable debate as to whether atrial fibrillation developing after cardiac surgery has a high risk of recurrence and thus whether extended anti-coagulation therapy to prevent thromboembolism can be beneficial. A recent meta-analysis analyzed 8 studies with a total of 1,157 participants monitored for new-onset PCSAF recurrence after discharge, all of whom were discharged in sinus rhythm and subsequently monitored by both noninvasive and invasive devices.¹⁷ Monitoring identified recurrence in 28.3 per 100 persons screened in the first 2 to 4 weeks after discharge using noninvasive techniques. Implanted devices identified recurrence in 61% to 100% of cases, suggesting that in-hospital PCSAF episodes are not transient. Most recurrences were asymptomatic and thus likely to be overlooked without the use of monitoring after hospital discharge.¹⁷

Evidence behind anticoagulation and benefits

In medical patients with chronic or recurrent atrial fibrillation, the cause-and-effect relationship between atrial arrhythmias and thromboembolic events has been thoroughly examined^18–21; however, this relationship has not been evaluated in the post-cardiac surgery setting. Current recommendations from the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) 2014 and 2019 updated guidelines is to use warfarin (to target an international normalized ratio [INR] 2–3) and novel oral anticoagulants in patients with history of stroke, transient ischemic attack, or CHA₂DS₂-VASc score ≥ 2, defined as patients with congestive heart failure, hypertension, age ≥ 75, diabetes, stroke, vascular disease, age 65 to 74, and female.^22,23

The question remains whether these guidelines are applicable to new-onset PCSAF in the postoperative period, taking into account the following facts:

• Risk of bleeding may be significant in the postoperative period

• CHA₂DS₂-VASc is a risk stratification tool that assesses annual stroke risk, however, has not been studied as an instrument for predicting postoperative stroke and embolic phenomena

• In current literature, high-quality evidence of early postoperative antithrombotic therapy benefits in thromboembolic complications is lacking.

Kollar and colleagues²⁴ described a retrospective study regarding benefits of anticoagulation in the postoperative period of 2,960 patients after CABG with 32 patients having had a postoperative stroke. The study was unique in that it examined the temporal relationship between postoperative atrial fibrillation and stroke. Seventeen of these patients continued to maintain sinus rhythm during their hospitalization. Of the remaining 15 patients, 9 had neurologic deficits before the first episode of atrial fibrillation. Of the 6 patients with atrial fibrillation preceding neurologic events, three strokes occurred within 1 week after spontaneous conversion to normal sinus rhythm. One patient with preoperative as well as intraoperative atrial fibrillation underwent emergency CABG surgery and woke up with a stroke. In the remaining two cases, the atrial fibrillation or atrial flutter episodes lasted less than 6 hours each before the onset of neurologic events. Authors concluded that aggressive anticoagulation as suggested in current guidelines could not have decreased the already low incidence of postoperative stroke.²⁴ The study, however, was underpowered making it difficult to draw a conclusion that is generalizable to a large cohort. An adequately powered prospective registry evaluating the benefits of anticoagulation in the early postoperative period is warranted.

Risk of postoperative bleeding with anticoagulation

The questionable rationale of early anticoagulation in reducing postoperative stroke is impacted by the risk of associated bleeding in the postoperative period. For instance, there was a significant increase in large pericardial effusions and tamponade occurring one week or more after surgery in a study of patients treated with warfarin compared with the antiplatelet control group, especially when excessively anticoagulated (INR above therapeutic target).²⁵

Bleeding other than at the surgical site might be relevant when determining use of anticoagulants, particularly with gastrointestinal hemorrhage. In a single-center, retrospective analysis of 9,017 patients undergoing cardiac surgery, the incidence of endoscopy-requiring gastrointestinal hemorrhage was 1.01%, and 30-day mortality was higher in patients who bled compared with patients who did not.²⁶ The study was limited in that only bleeding events requiring intervention were included.

HAS-BLED is a risk score, defined as hypertension, abnormal renal or liver function, stroke, bleeding history or predisposition, labile INR, elderly (age > 65), and drugs or alcohol concomitantly, that is often used to determine use of anticoagulation therapy by evaluating risks and benefits in the general population with atrial fibrillation that is not valvular. However, validity in patients after surgery has not been evaluated.²⁷ Thus, a high-quality risk stratification tool to identify bleeding in surgical patients would be of great clinical value.

Recommendations of professional societies

The AHA/ACC/HRS guidelines recommend considering using anticoagulation medication for patients who develop new-onset postoperative atrial fibrillation as administered for nonsurgical patients.²² The American College of Chest Physicians suggests weighing the AHA/ACC/HRS recommendations in the context of the usually transient and self-limited duration of new-onset PCSAF against the potential risk of bleeding and recommends starting anticoagulation therapy if atrial fibrillation persists 48 hours and beyond. They further state that therapy should be continued for 30 days after the return to normal sinus rhythm because of persistent atrial contraction impairment and possible enhanced risk of thrombosis following cardioversion to sinus rhythm.²⁸ The Canadian Cardiovascular Society Atrial Fibrillation Guidelines recommend continuing anticoagulation for new-onset PCSAF for a minimum of 6 weeks,²⁹ although the American College of Chest Physicians and AHA/ACC/HRS did not provide details regarding timing of initiation of antithrombotic therapy. A report from the European Association for Cardio-Thoracic Surgery does not recommend immediate full antithrombotic therapy when new-onset atrial fibrillation develops within 48 hours of cardiac surgery, due to increased risk of cardiac tamponade.³⁰ Table 1 provides a summary of these recommendations,^{22,23,28–30} and Figure 1 shows our proposed algorithm for management of new-onset PCSAF.

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Figure 1

Proposed algorithm for management of new-onset atrial fibrillation following cardiac surgery.

AF = atrial fibrillation; CHA₂DS₂-VASc = congestive heart failure, hypertension, age ≥ 75, diabetes, stroke, vascular disease, age 65 to 74, and female; PCSAF = post-cardiac surgery atrial fibrillation

Selection of drugs

The American College of Chest Physicians and AHA/ACC/HRS recommend anticoagulation therapy with warfarin, with or without heparin for atrial fibrillation.^22,28 Novel oral anticoagulants have been included in the 2014 and 2019 updated AHA/ACC/HRS guidelines.^22,23 More recently, the 2019 report added idarucizumab and andexanet alfa for the reversal of direct thrombin and activated factor Xa inhibitors, respectively.²³

In one retrospective review, patients were administered anticoagulation with either warfarin or novel oral anticoagulants for new-onset PCSAF in the postoperative period; both drug classes were found to be safe and effective methods of anticoagulation with no significant difference between outcomes of strokes, postoperative hemorrhage, and hospital length of stay.³¹ The study was small and limited to the hospital postoperative period. Two other small pilot studies compared edoxaban³² and apixaban³³ to warfarin for new-onset PCSAF and demonstrated safety and efficacy while suggesting larger scale clinical trials for further evaluation. A randomized clinical trial comparing rivaroxaban and warfarin for new-onset PCSAF is currently under way.³⁴

Monitoring of therapy and discontinuation of anticoagulants

There is a lack of evidence regarding monitoring following discharge for new-onset PCSAF patients who revert to sinus rhythm before discharge. Consequently, some hospitals have developed institutional policies regarding follow up and monitoring of patients that relies on expert opinion. For instance, a feasibility cross-sectional study with a unique idea of self-monitoring assessed 42 patients who had undergone cardiac surgery (CABG, valve surgery, or combination) for new-onset PCSAF recurrence using smart phone handheld electrocardiogram devices.³⁵ Study participants were instructed to record rhythm for 30 seconds, 4 times daily, for 4 weeks after discharge. Owing to the feasibility of the study, there was no control group, randomization, or blinding. Self-monitoring identified 24% with atrial fibrillation recurrence within 17 days of hospital discharge. Surprisingly, patients with atrial fibrillation recurrence were younger and had a lower CHA₂DS₂-VASc score than those without atrial fibrillation recurrence. Results should be interpreted with caution owing to the small sample size, infrequent self-monitoring, and study duration. Additional atrial fibrillation episodes may have been detected with a larger sample size and longer daily monitoring.