Is it time to treat post-operative atrial fibrillation just like regular atrial fibrillation?

This editorial refers to ‘Risk of stroke and other adverse outcomes in patients with perioperative atrial fibrillation 1 year after non-cardiac surgery’†, by D. Conen et al., on page 645. The next era of cardiovascular medicine in developed countries will be dominated by the need to address the healthcare and patient burdens of ageing-associated conditions such as atrial fibrillation (AF).1 The impact of AF extends widely, including a contribution to poor outcomes for patients after surgical procedures and unsustainable healthcare costs. The conventional thought is that post-operative AF is just a transient and self-limiting condition resulting from the surgical milieu (pro-inflammatory, intracellular electrolyte disturbance and surgery-specific factors). However, there is increasing evidence that AF frequently recurs and is associated with long-term adverse outcomes. In the context of cardiac surgery, we know that post-operative AF is not just an inconvenience; for example, in 16 169 consecutive patients who underwent isolated bypass surgery at a single US centre, survival rates at 10 years after surgery were 55% in those with post-operative AF requiring treatment, compared with 70% without post-operative AF.2 AF is frequently diagnosed after cardiac surgery, with 33% of patients developing post-operative AF in the Rate Control Versus Rhythm Control For Postoperative Atrial Fibrillation trial, increasing to ∼50% in those who also required valve surgery.3 However, post-operative AF is not just confined to cardiac surgery, occurring in 11% of patients undergoing general abdominal surgery across 13 studies.4 The implications of post-operative AF in the non-cardiac surgery setting are unclear. In this issue of the European Heart Journal, Conen et al. seek to address this knowledge gap and provide confirmation that AF, regardless of aetiology, is associated with a high risk of stroke and death that requires effective management.5 In a meta-analysis of randomized trials for the prevention of immediate post-operative AF after non-cardiac surgery (21 trials involving 11 608 patients), amiodarone and statins more than halved the incidence of post-operative AF with relative risks of 0.42 and 0.43, respectively.6 Beta-blockers also substantially reduced the risk of post-operative AF, but this was offset by an increased mortality risk [1.33; 95% confidence interval (CI) 1.03–1.37]. Angiotensin-converting enzyme inhibitors and calcium channel blockers were also shown to reduce post-operative AF in a meta-analysis of 22 trials in non-cardiac thoracic surgery (2891 patients).7 More-convincing and larger individual trials are available for patients undergoing cardiac surgery, and bring a degree of realism to the field. Despite positive results from smaller studies, patients randomized to rosuvastatin in the Statin Therapy In Cardiac Surgery trial had similar post-operative AF rates to those in the placebo arm (21.1 and 20.5%, respectively).8 Although amiodarone is effective at preventing post-operative AF in cardiac surgery patients,9 it was not shown to reduce hospital length of stay (with cardioversion as required) compared with patients randomized to rate control.3 Therefore, both the prevention of post-operative AF and acute management of patients without haemodynamic compromise are dependent on patient characteristics, patient preference, and local policies. The risk of long-term AF after a post-operative episode has not been extensively studied. In 571 patients after coronary artery bypass grafting, 25% of patients with post-operative AF developed recurrent AF during a median follow-up of 6 years compared with 3.6% of patients with no AF at surgery.10 In 163 patients after open heart surgery, 44% of those with post-operative AF had recurrent AF during a mean follow-up of 3.7 years, a nine-fold increase in risk.11 In both of these studies, the recurrence of AF is likely to have been underestimated as late detection used 12-lead electrocardiograms, hospital admission data, or short-duration monitoring. Data on AF recurrence after non-cardiac surgery are limited, but may be similar to cardiac surgery on long-term follow-up despite the different cardiovascular risk profiles of these patients.12 In the analysis by Conen et al., data from two large trials on non-cardiac post-operative AF are combined, PeriOperative ISchemic Evaluation (POISE) 1 and 2.5 From 18 117 patients, 404 (2.2%) developed post-operative AF requiring treatment or leading to clinical consequences. Rates of adverse events, including undefined stroke and mortality, were consistently elevated in patients with post-operative AF at 1 year, presumably despite optimal management of patients in the acute clinical setting. The lack of information on the subsequent therapeutic management of the AF is a limitation of the study, but the results do highlight that post-operative AF is not benign and has a similar adverse impact on patients to those undergoing cardiac surgery. Of particular interest is the similarity in stroke and death rates when comparing the study population with patients presenting with AF, but not in the context of surgery. In Figure 1, we demonstrate an indirect comparison with large AF cohorts with a similar risk profile [CHADS2=2, based on history of congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and prior stroke or transient ischaemic attack (2 points)]. With this information, the reluctance of clinicians to provide long-term oral anticoagulation could be questioned. Unfortunately, we lack any randomized trial data in this scenario of post-operative AF. In a Danish cohort study, the long-term benefit of anticoagulation was similar between patients with post-operative AF and a matched non-surgical AF cohort, despite a lower risk of thromboembolism in the former.13 For post-operative AF, they observed an adjusted hazard ratio (HR) for thromboembolism of 0.55 compared with those without anticoagulation (95% CI 0.32–0.95; P=0.03), and for the non-surgical patients the HR was 0.59 (95% CI 0.51–0.68; P < 0.001). In the aforementioned US cohort study, post-operative AF patients discharged on warfarin had significantly lower risk of death after mean follow-up of 6 years, with a HR of 0.78 compared with post-operative AF patients that were not anticoagulated (95% CI 0.66–0.92).2 As these analyses come from observational studies with prescription bias for anticoagulation use, interpretation is limited. However, they do reiterate the ongoing risk that patients with post-operative AF are exposed to and the potential value of long-term oral anticoagulation in patients at risk of thrombo-embolic disease. The balance of risk vs. benefit always requires re-evaluation, but the contemporary context of anticoagulant choice is very different compared to a time when clinicians could only offer warfarin to their patients. Risk factors and consequences of post-operative atrial fibrillation. Left panels are risk factors for post-operative atrial fibrillation, with the number of ‘+’ signs indicating the strength of relationship based on published studies (brackets indicate factors where not all studies show a consistent relationship). Right panel is an indirect comparison of adverse events from studies with a similar atrial fibrillation stroke risk, comparing post-operative non-cardiac surgery with non-surgical atrial fibrillation. Data obtained from: (1) van den Ham et al.,17 (2) Friberg et al.,18 (3) Conen et al.,5 (4) Olesen et al.,19 and (5) Henriksson et al.20 AF, atrial fibrillation; CHADS2, atrial fibrillation stroke risk score, based on history of congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and prior stroke or transient ischaemic attack (2 points); OAC, oral anticoagulant; post-op, post-operative; yr, year. Current cardiothoracic surgery guidelines recommend anticoagulation 12–48 h after the onset of post-operative AF, balancing the risk of bleeding after cardiac surgery.14 Despite increasing evidence of late recurrence of AF in these patients, most cardiac surgeons typically stop anticoagulation as soon as sinus rhythm is restored to avoid late complications related to bleeding. Much more solid data in the form of randomized trials are needed before most surgeons would reconsider and maintain anticoagulation in post-operative AF patients. Studies showing an increased incidence of late stroke and death among patients who develop post-operative AF also identify this group as being older, with significantly more comorbidities such as congestive heart failure, peripheral vascular disease, renal dysfunction, and airways disease. Despite this, post-operative AF appears to independently predict long-term mortality.15 These data, together with the current study in non-cardiac surgery, suggest that close surveillance is required in all patients presenting with post-operative AF. The concept of post-operative AF as a transient condition needs to be reconsidered in light of the data presented on the high (and likely underestimated) risk of recurrence, and the clinical impact on patient prognosis after both cardiac and non-cardiac surgery. The operative setting may merely be a ‘stress test’ that demonstrates the likelihood of future AF, and the consequences and complications arising from it. Rates of stroke and death in post-operative AF patients are comparable with those of patients with non-surgical AF. Typical AF patients receive oral anticoagulation based on their ongoing risk of stroke rather than the heart rhythm they display at that particular time point8, precisely because of the uncertain temporal relationship of AF episodes to stroke and difficulties in truly establishing AF recurrence.16 In the era of direct oral anticoagulants, perhaps it is time for post-operative AF to be treated in the same way as ‘regular’ AF, with life-long anticoagulation maintained in those with clinical risk factors for stroke (after appropriate modification in the immediate post-operative period to reduce bleeding complications). This could be of particular value for post-operative AF after non-cardiac surgery, where the AF ‘trigger’ is not directly related to pericardial or myocardial interference. There is clearly a need for randomized controlled trials, but in terms of patient safety, it may be prudent to encourage long-term anticoagulation in patients with post-operative AF at risk of stroke, pending further confirmation of this approach. D.K. is supported by a National Institute of Health Research (NIHR) Career Development Fellowship (CDF-2015-08-074). The opinions expressed in this paper are those of the authors and do not represent the NIHR or the UK Department of Health. Conflict of interest: D.