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Published on: February 26, 2013
Early Rhythm Control in Patients With Atrial Fibrillation and High Comorbidity Burden
Andreas Rillig1,2, Katrin Borof1, Günter Breithardt3,4
1Department of Cardiology, University Heart and Vascular Center (A.R., K.B., A.M., P.K.), University Medical Center Hamburg-Eppendorf, Germany.
Insights
Early rhythm control (ERC) benefits patients with atrial fibrillation and high stroke risk (CHA₂DS₂-VASc score ≥4). However, ERC may increase adverse events in patients with fewer comorbidities (CHA₂DS₂-VASc score <4).
Area of Science:
- Cardiology
- Clinical Trials
- Atrial Fibrillation Management
Background:
- The EAST-AFNET4 trial showed early rhythm control (ERC) reduces cardiovascular events in recent-onset atrial fibrillation (AF) with stroke risk factors.
- The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities remain unclear.
Purpose of the Study:
- To compare the effectiveness and safety of ERC versus usual care (UC) in patients with higher (CHA₂DS₂-VASc score ≥4) and lower comorbidity burden.
- To analyze ERC outcomes stratified by comorbidity burden.
Main Methods:
- Prespecified subanalyses of the EAST-AFNET4 trial.
- Patients were stratified into higher (CHA₂DS₂-VASc score ≥4) and lower (CHA₂DS₂-VASc score <4) comorbidity groups.
- Effectiveness (composite primary efficacy outcome) and safety (primary safety outcome) of ERC vs. UC were compared within strata.
Main Results:
- In patients with higher comorbidity burden (CHA₂DS₂-VASc score ≥4), ERC significantly reduced the primary efficacy outcome (HR, 0.64; P < 0.001) without increasing the primary safety outcome (HR, 0.84; P=0.175).
- In patients with lower comorbidity burden (CHA₂DS₂-VASc score <4), ERC did not reduce the primary efficacy outcome (HR, 0.93; P=0.56) and increased the primary safety outcome (HR, 1.39; P=0.019).
- Sex-stratified analysis showed significant interaction for safety outcomes when female sex was ignored (P=0.044).
Conclusions:
- Early rhythm control (ERC) is recommended for patients with recently diagnosed atrial fibrillation and a CHA₂DS₂-VASc score of 4 or higher to reduce adverse cardiovascular outcomes.
- Patients with fewer comorbidities (CHA₂DS₂-VASc score <4) may experience less favorable outcomes and increased safety risks with ERC compared to usual care.
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.
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