By Michael H. Crawford, MD, Editor

SYNOPSIS: Investigators compared post-coronary artery bypass graft (CABG) atrial fibrillation (AF) to non-surgical, non-valvular AF in a large cohort derived from the Danish health system database. Despite a lower rate of oral anticoagulant use compared to non-valvular AF patients and equivalent CHA2DS2-VASc scores, post-CABG AF demonstrated a lower risk of thromboembolism, death, and recurrent AF. These data do not support the concept that post-CABG AF is the same as traditional non-valvular AF regarding thromboembolic risk.

SOURCES: Butt JH, Xian Y, Peterson ED, et al. Long-term thromboembolic risk in patients with postoperative atrial fibrillation after coronary artery bypass graft surgery and patients with nonvalvular atrial fibrillation. JAMA Cardiol 2018;3:417-424.

Healey JS, McIntyre WF, Whitlock RP. Late stroke after coronary artery bypass grafting. JAMA Cardiol 2018;3:425-426.

New onset post-operative atrial fibrillation (POAF) is a common, but usually self-limiting, complication of coronary artery bypass graft surgery (CABG). Although generally thought to be relatively benign, there are few data on its long-term implications. Current guidelines give little guidance on the role of oral anticoagulants (OAC) in POAF.

Investigators from Denmark performed a retrospective cohort study of stroke prophylaxis and the long-term risk of thromboembolism (TE) in 2,108 patients undergoing first isolated CABG who developed new POAF. These patients were matched by age, sex, and CHA2DS2-VASc scores with 8,432 patients with non-surgical, non-valvular AF (NVAF). Inclusion criteria for the POAF patients included no prior history of AF, no prescription for OAC ≤ 6 months prior to surgery, no history of deep venous thrombosis or pulmonary embolism, and survival until discharge from the hospital. The NVAF comparison group met similar criteria. The primary outcome was any TE. Secondary endpoints included death and recurrent AF requiring hospitalization. The mean age of the POAF group was 69 years, and 82% were men. Their mean CHA2DS2-VASc score was 3.1, which was the same as the NVAF group. However, there were significant differences in many co-morbidities between the two groups. OAC therapy was started within 30 days in 8.4% of POAC subjects and 43% of NVAF subjects. Anti-platelet therapy was employed in 79% of the POAF group and a little over half of NVAF patients. Median follow-up was five years in the POAF group and 3.5 years in the NVAF group. The incidence of TE was 18.3 per 1,000 person years in POAF patients and 29.7 in NVAF patients.

By multivariate analysis, the incidence of TE was significantly lower in the POAF group (adjusted hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.55-0.81; P < 0.001). OAC therapy was associated with a significantly lower risk of TE in both groups compared to those not treated with OAC. POAF was associated with a lower risk of death compared to NVAF (HR, 0.55; 95% CI, 0.49-0.61; P < 0.001). However, OAC use was only associated with a lower risk of death in the NVAF group. Also, in POAF patients, the risk of recurrent AF was significantly lower than in the NVAF patients (HR, 0.29; 95% CI, 0.25-0.34; P < 0.001), but higher than in those post-operative patients who did not develop AF (HR, 2.27; 95% CI, 1.84-2.80; P < 0.001). Additionally, mortality was higher in POAF patients compared to post-operative patients without AF (HR, 1.32; 95% CI, 1.18-1.47; P < 0.001). The authors concluded that these data do not support the concept that POAF is equivalent to NVAF regarding long-term TE risks.

COMMENTARY

Previous studies have shown that POAF in CABG patients usually disappears by six weeks post-operation, no matter what therapy is given, which supports the notion that it is largely due to the systemic inflammatory response to surgery. Also, prior studies have shown a higher incidence of TE in the first 30 days in those with POAF compared to those without, but the incidence of long-term TE has been unclear, and few studies have contained data about long-term OAC use. In this observational study, only 8% of POAF patients received OAC compared to 43% of NVAF patients. Yet, POAF patients demonstrated a much lower incidence of TE despite equivalent CHA2DS2-VASc scores. Also, death and recurrent hospitalization for AF was lower in POAF subjects vs. NVAF subjects. The authors concluded that POAF is more benign than typical NVAF, but stopped short of making OAC recommendations.

Both the U.S. and European guidelines state that it is reasonable to consider OAC therapy in POAF patients, but don’t elaborate further. The critical issue is that most POAF probably is a transient phenomenon that does not necessitate long-term OAC therapy, but some of these patients may resemble NVAF patients who happen to have received the diagnosis of AF after CABG. How do we identify these higher-risk POAF patients? Unfortunately, this study does not address that issue and the authors recommended conducting a randomized, controlled trial. Until such a trial is performed, how should we proceed? It appears that short-term OAC should be given, if feasible post-operatively, since it reduces TE compared to those with POAF, who did not receive it in this study and in others. The decision about long-term OAC should be made after considering other risk factors for recurrent AF or TE. Perhaps those with very large atria or very high CHA2DS2-VASc scores should receive OACs long term. Certainly those with persistent AF or recurrent AF should. Perhaps an ambulatory ECG monitor should be employed after the return of sinus rhythm, but within 8-12 weeks post-operatively.

The strength of this trial is the complete information available through the Danish health system, especially regarding OAC use. The weaknesses, in addition to its observational design, are that we have no information about the duration of POAF or the rhythm at discharge. Also, we don’t know the type of AF the NVAF patients had. Despite these weaknesses, this study adds to our knowledge in this area and helps inform the clinical judgment required to manage patients with POAF after CABG.