TY - JOUR
T1 - Early Rhythm Control in Patients With Atrial Fibrillation and High Comorbidity Burden
AU - Rillig, Andreas
AU - Borof, Katrin
AU - Breithardt, Günter
AU - Camm, A John
AU - J G M Crijns, Harry
AU - Goette, Andreas
AU - Kuck, Karl-Heinz
AU - Metzner, Andreas
AU - Vardas, Panos
AU - Vettorazzi, Eik
AU - Wegscheider, Karl
AU - Zapf, Antonia
AU - Kirchhof, Paulus
N1 - Funding Information:
EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial–Atrial Fibrillation Network) was supported by a grant from the German Ministry of Education and Research (grant 01 GI 0204), the German Center for Cardiovascular Research, the Atrial Fibrillation Network, the European Heart Rhythm Association, St Jude Medical–Abbott, Sanofi, and the German Heart Foundation. These analyses received additional support from the European Union (grant agreement 633196 [CATCH ME (Characterizing Atrial Fibrillation by Translating Its Causes Into Health Modifiers in the Elderly)] to Dr Kirchhof and the Atrial Fibrillation Network; grant agreement EU IMI 116074 [BigData@Heart] to Dr Kirchhof; and grant agreement 965286 [MAESTRIA (Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation)] to the Atrial Fibrillation Network), the British Heart Foundation (grants FS/13/43/30324, PG/17/30/32961, PG/20/22/35093, and AA/18/2/34218 to Dr Kirchhof), and the Leducq Foundation (to Dr Kirchhof).
Funding Information:
Dr Rillig received consultant fees from Medtronic, KODEX-EPD, and Biosense Webster and travel grants and lecture fees from Medtronic, CardioFocus, Biosense Webster, Abbott, Boehringer Ingelheim, Philips KODEX-EPD, Ablamap, Bayer, and Novartis. Dr Metzner received speaker honoraria, travel grants, and consultant fees from Medtronic, KODEX-EPD, Biosense Webster, CardioFocus, and Boston Scientific. Dr Kirchhof reports holding patent WO2015140571 on atrial fibrillation therapy, licensed to the University of Birmingham, and patent WO2016012783 on markers for atrial fibrillation, licensed to the University of Birmingham. Dr Camm reports receiving consulting fees from Sanofi and grant support and consulting fees from Abbott. Dr Goette reports receiving lecture fees and consulting fees from Daiichi Sankyo, Sanofi Aventis, and Omeicos and lecture fees from Abbott, Bristol-Myers Squibb (BMS)–Pfizer, Medtronic, Boehringer Ingelheim, AstraZeneca, and Berlin Chemie and was partially supported by EU Grant Horizon 2020 MAESTRIA Consortium (grant 965286). E. Vettorazzi reports receiving grant support from Biotronik. Dr Vardas reports receiving consulting fees from Servier International and Hygeia Hospitals Group, HHG, and European Society of Cardiology. Dr Wegscheider reports receiving grant support and lecture fees from Biotronik, lecture fees from Boston Scientific, and consulting fees from Novartis. Dr Breithardt has nothing to declare with regard to this substudy of EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial–Atrial Fibrillation Network). Dr Kuck has nothing to declare with regard to this subgroup analysis of EAST-AFNET4. K. Borof has nothing to declare with regard to this subgroup analysis of EAST-AFNET4. Dr Zapf reports receiving grant support from Biotronik. Dr Crijns has nothing to declare with regard to this subanalysis of EAST-AFNET4. The other authors report no conflicts.
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/9/13
Y1 - 2022/9/13
N2 - BACKGROUND: The randomized EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial-Atrial Fibrillation Network) demonstrated that early rhythm control (ERC) reduces adverse cardiovascular outcomes in patients with recently diagnosed atrial fibrillation and stroke risk factors. The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities is not known.METHODS: These prespecified subanalyses of EAST-AFNET4 compared the effectiveness and safety of ERC with usual care (UC) stratified into patients with higher (CHA2DS2-VASc score ≥4) and lower comorbidity burden. Sensitivity analyses ignored sex (CHA2DS2-VA score).RESULTS: EAST-AFNET4 randomized 1093 patients with CHA2DS2-VASc score ≥4 (74.8±6.8 years, 61% female) and 1696 with CHA2DS2-VASc score <4 (67.4±8.0 years, 37% female). ERC reduced the composite primary efficacy outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome in patients with CHA2DS2-VASc score ≥4 (ERC, 127/549 patients with events; UC, 183/544 patients with events; hazard ratio [HR], 0.64 [0.51-0.81]; P < 0.001) but not in patients with CHA2DS2-VASc score <4 (ERC, 122/846 patients with events; UC, 133/850 patients with events; HR, 0.93 [0.73-1.19]; P=0.56, Pinteraction=0.037). The primary safety outcome (death, stroke, or serious adverse events of rhythm control therapy) was not different between study groups in patients with CHA2DS2-VASc score ≥4 (ERC, 112/549 patients with events; UC, 132/544 patients with events; HR, 0.84 [0.65, 1.08]; P=0.175), but occurred more often in patients with CHA2DS2-VASc scores <4 randomized to ERC (ERC, 119/846 patients with events; UC, 91/850 patients with events; HR, 1.39 [1.05-1.82]; P=0.019, Pinteraction=0.008). Life-threatening events or death were not different between groups (CHA2DS2-VASc score ≥4, ERC, 84/549 patients with event, UC, 96/544 patients with event; CHA2DS2-VASc scores <4, ERC, 75/846 patients with event, UC, 73/850 patients with event). When female sex was ignored for the creation of higher and lower risk groups (CHA2DS2-VA score), the Pinteraction was not significant for the primary efficacy outcome (P=0.25), but remained significant (P=0.044) for the primary safety outcome.CONCLUSIONS: Patients with recently diagnosed atrial fibrillation and CHA2DS2-VASc score ≥4 should be considered for ERC to reduce cardiovascular outcomes, whereas those with fewer comorbidities may have less favorable outcomes with ERC.REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT01288352; URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2010-021258-20; URL: https://www.isrctn.com/; Unique identifier: ISRCTN04708680.
AB - BACKGROUND: The randomized EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial-Atrial Fibrillation Network) demonstrated that early rhythm control (ERC) reduces adverse cardiovascular outcomes in patients with recently diagnosed atrial fibrillation and stroke risk factors. The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities is not known.METHODS: These prespecified subanalyses of EAST-AFNET4 compared the effectiveness and safety of ERC with usual care (UC) stratified into patients with higher (CHA2DS2-VASc score ≥4) and lower comorbidity burden. Sensitivity analyses ignored sex (CHA2DS2-VA score).RESULTS: EAST-AFNET4 randomized 1093 patients with CHA2DS2-VASc score ≥4 (74.8±6.8 years, 61% female) and 1696 with CHA2DS2-VASc score <4 (67.4±8.0 years, 37% female). ERC reduced the composite primary efficacy outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome in patients with CHA2DS2-VASc score ≥4 (ERC, 127/549 patients with events; UC, 183/544 patients with events; hazard ratio [HR], 0.64 [0.51-0.81]; P < 0.001) but not in patients with CHA2DS2-VASc score <4 (ERC, 122/846 patients with events; UC, 133/850 patients with events; HR, 0.93 [0.73-1.19]; P=0.56, Pinteraction=0.037). The primary safety outcome (death, stroke, or serious adverse events of rhythm control therapy) was not different between study groups in patients with CHA2DS2-VASc score ≥4 (ERC, 112/549 patients with events; UC, 132/544 patients with events; HR, 0.84 [0.65, 1.08]; P=0.175), but occurred more often in patients with CHA2DS2-VASc scores <4 randomized to ERC (ERC, 119/846 patients with events; UC, 91/850 patients with events; HR, 1.39 [1.05-1.82]; P=0.019, Pinteraction=0.008). Life-threatening events or death were not different between groups (CHA2DS2-VASc score ≥4, ERC, 84/549 patients with event, UC, 96/544 patients with event; CHA2DS2-VASc scores <4, ERC, 75/846 patients with event, UC, 73/850 patients with event). When female sex was ignored for the creation of higher and lower risk groups (CHA2DS2-VA score), the Pinteraction was not significant for the primary efficacy outcome (P=0.25), but remained significant (P=0.044) for the primary safety outcome.CONCLUSIONS: Patients with recently diagnosed atrial fibrillation and CHA2DS2-VASc score ≥4 should be considered for ERC to reduce cardiovascular outcomes, whereas those with fewer comorbidities may have less favorable outcomes with ERC.REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT01288352; URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2010-021258-20; URL: https://www.isrctn.com/; Unique identifier: ISRCTN04708680.
U2 - 10.1161/circulationaha.122.060274
DO - 10.1161/circulationaha.122.060274
M3 - Article
C2 - 35968706
SN - 0009-7322
VL - 146
SP - 836
EP - 847
JO - Circulation
JF - Circulation
IS - 11
ER -