No Anticoagulation Benefit, High Bleeding Risk Seen in Patients With Secondary A-fib

Oral anticoagulation does not reduce the risk of ischemic stroke in patients with atrial fibrillation that results from ACS, acute pulmonary disease, or sepsis, but it does appear to increase the risk of bleeding, at least in patients with acute pulmonary disease, according to the results of a new analysis.

The study raises questions as to whether the risk of stroke and bleeding may differ in patients with secondary A-fib compared with primary A-fib, say researchers, adding that in the absence of clear-cut data, physicians need to use their judgement when treating patients in whom the arrhythmia is not the primary diagnosis.

Lead investigator Michael Quon, MD (McGill University Health Centre, Montreal, Canada) said the study results don’t support the routine use of anticoagulation in patients with secondary A-fib related to ACS, acute pulmonary disease, or sepsis. 

“Are we saying that anticoagulation should not be administered in any of these patients? No,” he told TCTMD. “We’re clearly not identifying a reduction in ischemic stroke, but we do think this should be carefully considered at the individual level in terms of decisions around anticoagulation.”

Angelo Biviano, MD (Columbia University Medical Center, New York, NY), who was not involved in the study, told TCTMD that most physicians would consider oral anticoagulation in patients with A-fib even if the arrhythmia was a secondary diagnosis.

“A good percentage of patients who have what is thought to be a trigger or a reason for atrial fibrillation wind up over the course of several years’ follow-up having other episodes of atrial fibrillation not necessarily caused by the same triggering event,” he said. “The more we monitor, the more we see [atrial fibrillation]. And in the setting of the hospital, where patients are ill, it’s certainly a captive audience, but that doesn’t mean the patient hadn’t had it before in their lives or might not have it again.”

Secondary A-fib Not Uncommon

The analysis, published online September 27, 2017, ahead of print in JACC: Clinical Electrophysiology, included 2,304 patients participating in a provincial registry who were 65 years and older with a primary diagnosis of a known reversible cause of A-fib. Patients with a previous diagnosis or hospital admission for A-fib were excluded from the analysis, as were those with a recent admission for CABG or other cardiac surgery.

To TCTMD, Quon said secondary A-fib is not infrequently encountered in the hospital setting. After consistently observing the arrhythmia in these patient populations, he and his colleagues questioned whether anticoagulation was indicated at the time of discharge.

Few clinical guidelines provide direction, although the American Heart Association recommends anticoagulation in patients with ACS, new-onset A-fib, and a CHA2DS2-VASc risk score ≥ 2. For patients with acute pulmonary disease or sepsis, they recommend treating the primary diagnosis and then assessing the patient’s risk profile and duration of A-fib when considering anticoagulation therapy. Canadian and European guidelines do not make specific anticoagulation recommendations for these patients, said Quon.

“I do believe it’s a bit of a question that’s not clearly defined,” he said. “The confusion or debate is because there’s not a lot in the way of studies looking at the benefits of anticoagulation [in these patients with secondary A-fib] . . . . Even in this study, the rates of anticoagulation were significantly lower in this cohort of secondary atrial fibrillation when compared with similar studies of primary atrial fibrillation. It seems like physicians are treating these patients differently and it’s not really guided by evidence or guideline-based recommendations.”    

ACS was the primary diagnosis for 827 patients and acute pulmonary disease, including chronic obstructive pulmonary disease and influenza/pneumonia, for 1,375 patients. Although most patients had high CHADS2 scores—60.9% to 66.5% had a score of 2 or greater—oral anticoagulation was prescribed within the first 30 days of discharge for 38.4% of patients with ACS, 34.1% of those with acute pulmonary disease, and 27.7% of those with sepsis.

Follow-up ranged from 3.1 years for patients with secondary A-fib resulting from acute pulmonary disease and sepsis to 3.6 years for those with a primary diagnosis of ACS. The overall ischemic stroke rate was 5.4%, 3.9%, and 5.9% in the groups with primary diagnoses of ACS, acute pulmonary disease, and sepsis, respectively. Anticoagulant use, however, did not lower the risk of ischemic stroke when compared with patients not receiving anticoagulation.

The overall incidence of bleeding was 13.5% and 13.4% in patients with ACS and acute pulmonary disease, respectively, and 19.6% in those with sepsis. Oral anticoagulation was associated with an increased risk of bleeding in patients with acute pulmonary disease, but not in those with ACS or sepsis.

Quon said he expected at least a trend toward benefit with anticoagulation, although he acknowledged the incidence of stroke is low and the study might be underpowered to significantly detect a reduction in ischemic stroke.

Different Patients Than Primary A-fib

Regarding the lack of benefit, Biviano called the findings “provocative” and hypothesis-generating, saying they speak to the larger point that medical care needs to be personalized. He noted that physicians prescribing oral anticoagulants are always aiming to strike the right balance between managing the risk of stroke and bleeding. This can be problematic in a secondary A-fib population given the lack of data.

“A secondary AF population that was studied is likely different from the traditional validation cohorts of the CHADS2 and CHA2DS2-VASc studies,” he said. “So the results aren’t too surprising in that anticoagulation as an overall strategy to reduce stroke would be different from other trials. It’s a different group of patients with a different relative balance between the bleeding and stroke risks.”  

Like Quon, Biviano said the analysis might not be sufficiently powered to identify differences in stroke outcomes between those who were anticoagulated and those who were not. The results, however, suggest further studies are needed to assess the benefit of anticoagulation in a large, randomized trial.

“At the end of the day, it’s still a judgement call, and part of the art of medicine,” said Biviano. “But this group is likely a different patient group in terms of patient characteristics, so their relative risk of stroke and bleeding are likely different. It’s great that a study like this comes out to point this out.”