Atrial Fibrillation: Updates in Screening, Surgical Ablation, and Anticoagulation Use

Atrial fibrillation (AF) is an important risk factor for ischemic stroke. Individuals with AF are 5 times more likely to have a stroke than individuals without AF, and AF is diagnosed for the first time in 10% of patients with acute ischemic stroke.^1,2

The cornerstone of stroke prevention therapy in AF is treatment with anticoagulant agents, which include both vitamin K and non-vitamin K oral anticoagulants (NOACs).² Surgical ablation procedures are also performed to reduce the risk of AF recurrence.³

Recent data have shed new insights on the screening and management of AF. Cardiology Advisor spoke with Ben Freedman, MBBS, PhD, from the Heart Research Institute and University of Sydney in Australia, about updated AF screening recommendations; Xiaoxi Yao, PhD, from the Mayo Clinic in Rochester, Minnesota, about NOAC use in patients with renal dysfunction; and Vinay Badhwar, MD, from the West Virginia University Heart and Vascular Institute in Morgantown, about outcomes and costs of surgical ablation for AF.

Opportunistic Screening for AF

Asymptomatic patients ≥65 years old should be routinely screened for AF with single-time point methods such as pulse-taking, according to a white paper by AF-SCREEN that was published in Circulation.¹ The European Society of Cardiology 2016 guidelines advocate this approach to AF screening, but the American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines do not make specific recommendations for AF screening.^4,5

The AF-SCREEN international collaboration, of which Dr Freedman is a co-founder, was formed to “promote discussion and research about screening for unknown or undertreated AF to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs.”¹

The group reported that screening for AF at a single time point, such as with pulse palpation or a handheld electrocardiogram (ECG) recording device, detects undiagnosed AF in 1.4% of the population aged 65 years and older.¹

“These patients are asymptomatic, yet they have a similar adverse prognosis of stroke and death as patients who have symptomatic AF,” Dr Freedman said.

Based on these findings, AF-SCREEN recommends using single-time point screening for AF in individuals ≥65 years old and considering twice-daily screening for 2 weeks in individuals >75 years old, and in younger people at increased risk for AF or stroke.¹

“About 33% of all ischemic strokes are related to AF, and most of them are preventable,” Dr Freedman noted. “Twenty percent occur in people with known AF who are not treated with anticoagulation, and 10% occur in people with previously unknown AF that could have been predicted by screening.”

“The key point for practicing physicians is that a simple thing like feeling the pulse will actually be quite effective in detecting irregularity. It used to be part of the physical examination, but it [is] often not done,” Dr Freedman said. The AF-SCREEN group also recommends screening for AF with a handheld ECG device, which produces a single-lead ECG required for AF diagnosis, and is more accurate than pulse palpation.¹

While AF-SCREEN recommends opportunistic screening for AF, calling for systematic screening (ie, screening all patients ≥65 years old with 12-lead ECGs) may require additional robust evidence from randomized controlled trials. “We feel that the evidence is already strong, but additional large studies showing that the part of the population that was screened had fewer strokes and deaths than the part that was not screened, would strengthen the evidence base for systematic screening,” Dr Freedman said.

NOAC Use in Renal Impairment

In clinical practice, a sizeable proportion of patients with AF and significant renal impairment are overdosed with NOACs, which may lead to worse safety outcomes without any reduction in stroke risk. Many patients with AF and mild or normal renal function are on inappropriately low doses of NOACs, putting them at greater risk for stroke without any safety benefit. These study results were published in the Journal of the American College of Cardiology.²

NOAC dosing must be adjusted for renal function in order to avoid increased bleeding risk in the case of overdosing and increased stroke risk with underdosing.² Registry data suggest that up to 50% of patients with renal dysfunction receive inappropriately high doses of NOACs, while up to 15% of patients with mild to normal renal function were treated with reduced doses of NOACs.^6,7 However, these findings from highly selective registries may not reflect patterns of NOAC dosing in the general population with AF, and data on the clinical effects of underdosing and overdosing are lacking.²

Dr Yao and colleagues sought to determine the patterns of NOAC dosing for AF in routine clinical practice and the impact of inappropriate dosing on safety and efficacy outcomes using patient data from an insurance claims database.²

Of 14,865 patients with AF treated with a NOAC (dabigatran, rivaroxaban, or apixaban), 1473 had a renal indication for dose reduction. More than 40% of these patients received standard doses of their NOAC. Overdosing was associated with higher rates of major bleeding (hazard ratio [HR], 2.19) but no reduction in stroke risk.²

Approximately 13% of 13,392 patients with no renal indication for dose reduction received reduced NOAC doses. In patients treated with apixaban, patients who were underdosed were more likely to experience stroke (HR, 4.87) with no decease in major bleeding risk compared with patients receiving the standard dose. No significant relationships between underdosing and clinical outcomes were found for rivaroxaban or dabigatran.²

“Overdosing is likely a result of not knowing patients’ renal function, and could be avoided by regular monitoring,” Dr Yao said.

“However, underdosing is a more complex problem, because it is often an effort of trying to avoid bleeding,” she noted. “Our study suggested that underdosing to avoid bleeding is not without cost. By underdosing, physicians could expose patients to a higher risk of stroke and should be aware of this tradeoff between stroke and bleeding,” Dr Yao said.

Surgical Ablation for AF

Surgical ablation for AF in patients undergoing coronary artery bypass grafting (CABG) increases inpatient healthcare costs, but not perioperative mortality and stroke risk. However, mortality at 1 year is significantly reduced in patients treated with surgical ablation compared with patients who are not treated with surgical ablation. These study results were published in the European Journal of Cardio-Thoracic Surgery.³

“Atrial fibrillation alone is an independent marker of short term morbidity and mortality following any cardiac operation,” Dr Badhwar said. Surgical ablation for AF is usually performed in conjunction with other cardiac procedures and lowers the risk of recurrent AF. But the impact of surgical ablation on costs and survival in patients with AF undergoing CABG were unclear until recently.³

Researchers, led by J. Scott Rankin, MD, from the West Virginia University Heart and Vascular Institute, and Dr Badhwar evaluated the inpatient costs and perioperative and long-term outcomes of surgical ablation for AF performed concurrently with CABG. Patient information was obtained from a Medicare inpatient admissions database.³

Of 3745 patients with AF undergoing CABG, 17% received surgical ablation for AF. Patients in the surgical ablation group had fewer preoperative comorbidities than patients in the no surgical ablation group, including recent heart failure, renal failure, or chronic lung disease (P <.05 for all comparisons).³

Mortality at 90 days was similar in both groups. However, mortality rates between 90 days to 1 year were significantly lower in the surgical ablation group than in the no surgical ablation group (hazard ratio [HR], 0.58; P =.03).³

Inpatient healthcare costs were higher in patients with surgical ablation than in patients without surgical ablation for the initial admission (HR, 1.11; P <.01) and at 1 year (HR, 1.06; P =.02).³

Patients who received surgical ablation were also more likely to require cardiovascular implantable electronic device implantation at 1 year (HR, 1.20; P =.01).³

“The most important finding of our study is that, after risk adjustment, the 1-year risk of death in patients who underwent surgical ablation was nearly half that of those who did not,” Dr Badhwar said. “Adding a surgical ablation procedure to patients going for a CABG did not increase operative risk, and the slight increment in cost is likely accounted for by the device disposables.”

According to Dr Badhwar, longer-term data are needed on the costs and outcomes of surgical ablation for AF during CABG. “What happens after 1 year? Is the survival benefit with surgical ablation still maintained, and does the cost equation still remain relevant? We are submitting a paper with 2-year data that may actually answer these questions.”

References

1. Freedman B, Camm J, Calkins H, et al. Screening for atrial fibrillation: a report of the AF-SCREEN international collaboration. Circulation. 2017;135(19):1851-1867. doi:10.1161/CIRCULATIONAHA.116.026693
2. Yao X, Shah ND, Sangaralingham LR, Gersh BJ, Noseworthy PA. Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J Am Coll Cardiol. 2017;69(23):2779-2790. doi:10.1016/j.jacc.2017.03.600
3. Rankin JS, Lerner DJ, Braid-Forbes MJ, Ferguson MA, Badhwar V. One-year mortality and costs associated with surgical ablation for atrial fibrillation concomitant to coronary artery bypass grafting† [published online May 2, 2017]. Eur J Cardiothorac Surg. doi:10.1093/ejcts/ezx126
4. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-2962. doi:10.1093/eurheartj/ehw210
5. January CT, Wann LS, Alpert JS, et al; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):e199-e267. doi:10.1161/CIR.0000000000000041 
6. Steinberg BA, Holmes DN, Piccini JP, et al; Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Investigators and Patients. Early adoption of dabigatran and its dosing in US patients with atrial fibrillation: results from the outcomes registry for better informed treatment of atrial fibrillation. J Am Heart Assoc. 2013;2(6):e000535. doi:10.1161/JAHA.113.000535
7. Camm AJ, Amarenco P, Haas S, et al; XANTUS Investigators. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J. 2016;37(14):1145-1153. doi:10.1093/eurheartj/ehv466