Anticoagulation, therapy of concomitant conditions, and early rhythm control therapy: a detailed analysis of treatment patterns in the EAST - AFNET 4 trial

Abstract

Aims: Treatment patterns were compared between randomized groups in EAST-AFNET 4 to assess whether differences in anticoagulation, therapy of concomitant diseases, or intensity of care can explain the clinical benefit achieved with early rhythm control in EAST-AFNET 4.

Methods and results: Cardiovascular treatment patterns and number of visits were compared between randomized groups in EAST-AFNET 4. Oral anticoagulation was used in >90% of patients during follow-up without differences between randomized groups. There were no differences in treatment of concomitant conditions between groups. The type of rhythm control varied by country and centre. Over time, antiarrhythmic drugs were given to 1171/1395 (84%) patients in early therapy, and to 202/1394 (14%) in usual care. Atrial fibrillation (AF) ablation was performed in 340/1395 (24%) patients randomized to early therapy, and in 168/1394 (12%) patients randomized to usual care. 97% of rhythm control therapies were within class I and class III recommendations of AF guidelines. Patients randomized to early therapy transmitted 297 166 telemetric electrocardiograms (ECGs) to a core lab. In total, 97 978 abnormal ECGs were sent to study sites. The resulting difference between study visits was low (0.06 visits/patient/year), with slightly more visits in early therapy (usual care 0.39 visits/patient/year; early rhythm control 0.45 visits/patient/year, P < 0.001), mainly due to visits for symptomatic AF recurrences or recurrent AF on telemetric ECGs.

Conclusion: The clinical benefit of early, systematic rhythm control therapy was achieved using variable treatment patterns of antiarrhythmic drugs and AF ablation, applied within guideline recommendations.

Keywords: Ablation; Antiarrhythmic drugs; Anticoagulation; Atrial fibrillation; Cardiovascular death; Heart failure; Rhythm control therapy; Stroke.

Figure 1

Anticoagulation therapy in patients randomized to early rhythm control (left panel) and usual care (right panel) in the EAST-AFNET 4 population at discharge from randomization, 1 year, and 2 years of follow-up. There was no difference in anticoagulation therapy between randomized groups. A combination of both was very rare and therefore the yellow bars are hardly visible. ^aCombination of both can raise due to changes of medication between visits.

Figure 2

(A) Use of inhibitors of the renin–angiotensin–aldosterone system in patients randomized to early rhythm control (left panel) and usual care (right panel) in the EAST-AFNET 4 population.(B) Systolic and diastolic blood pressure during the in-person visits, split by randomized groups. Blood pressure was not different between randomized groups. ^aAll Sacubitril and Valsartan are given only in combination with other medications.

Figure 3

Use of any rate controlling therapies in patients randomized to early rhythm control (left panel) and usual care (right panel) in the EAST-AFNET 4 population. This display includes antiarrhythmic drugs with rate controlling properties, namely amiodarone, dronedarone, propafenone, and sotalol. The use of these medications often obviates the need for additional rate-controlling medication, explaining the lower use of beta blockers, calcium channel antagonists, or digoxin shown in A.

Figure 4

(A) Number of in-person visits split by randomized group. There were 2710 in-person visits in patients randomized to usual care (1.94 visits/patient) and 2974 in-person visits in patients randomized to early rhythm control (2.13 visits/patient) (P < 0.001). (B) Timing of in-person follow-up visits split by randomized group and by visit type. All numbers are displayed as number of visits per day.

Figure 5

(A) Sankey Plot of rhythm control treatment over time per group. Shown is the proportion of patients receiving antiarrhythmic drugs (AAD) and AF ablation (ablation) at each of the scheduled visits, split by randomized groups, and the proportion of patients changing from one type of therapy to the other. (B) Time to first AF ablation split by randomized group (Aalen–Johansen cumulative incidence curve). AF ablation was more often used in patients randomized to early therapy, with a steady increase in both randomized groups over time. At 2 years, 270/1395 (19.4%) patients randomized to early therapy had undergone AF ablation, while 97/1394 (7.0%) patients randomized to usual care had undergone ablation.

Figure 6

(A) Multivariate analysis of potential factors influencing the decision to manage patients without rhythm control therapy (None, left panel), to perform AF ablation (middle panel), and to initiate antiarrhythmic drug therapy (AAD, right panel) at any time. The decision to manage without rhythm control therapy was almost entirely driven by randomized group. The decision to perform AF ablation was also influenced by younger age, randomization in an ablation site, diabetes, AF pattern, and country. AF type first, first episode or paroxysmal, persistent, persistent or long-standing persistent; ET, early treatment; Left ventricular hypertrophy on echocardiography was defined based on the inclusion criterium (>15 mm wall thickness); Severe CAD, severe coronary artery disease (previous myocardial infarction, CABG, or PCI); Stable heart failure was defined as either NYHA stage II or LVEF < 50%; TIA, transient ischaemic attack; UC, usual care. (B) Choice of initial rhythm control therapy displayed by centre. Displayed is the proportion of patients receiving each rhythm control therapy option in each centre, limited to centres that initiated rhythm control therapy in at least five patients. There are clear centre-based preferences in the choice of initial antiarrhythmic drug therapy, with individual sites using AF ablation, flecainide, propafenone, dronedarone, or other antiarrhythmic drugs in most patients initially. Therapy choices were guideline-conform in almost all patients.