Dronedarone for the treatment of atrial fibrillation with concomitant heart failure with preserved and mildly reduced ejection fraction: a <scp>post‐hoc</scp> analysis of the <scp>ATHENA</scp> trial
Bibliographic record
Abstract
Aims Limited therapeutic options are available for the management of atrial fibrillation/flutter (AF/AFL) with concomitant heart failure (HF) with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF). Dronedarone reduces the risk of cardiovascular events in patients with AF, but sparse data are available examining its role in patients with AF complicated by HFpEF and HFmrEF. Methods and results ATHENA was an international, multicentre trial that randomized 4628 patients with paroxysmal or persistent AF/AFL and cardiovascular risk factors to dronedarone 400 mg twice daily versus placebo. We evaluated patients with (i) symptomatic HFpEF and HFmrEF (defined as left ventricular ejection fraction [LVEF] >40%, evidence of structural heart disease, and New York Heart Association class II/III or diuretic use), (ii) HF with reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVEF ≤40%), and (iii) those without HF. We assessed effects of dronedarone versus placebo on death or cardiovascular hospitalization (primary endpoint), other key efficacy endpoints, and safety. Overall, 534 (12%) had HFpEF or HFmrEF, 422 (9%) had HFrEF or left ventricular dysfunction, and 3672 (79%) did not have HF. Patients with HFpEF and HFmrEF had a mean age of 73 ± 9 years, 37% were women, and had a mean LVEF of 57 ± 9%. Over a mean follow‐up of 21 ± 5 months, dronedarone consistently reduced risk of death or cardiovascular hospitalization (hazard ratio 0.76; 95% confidence interval 0.69–0.84) without heterogeneity based on HF status ( p interaction >0.10). This risk reduction in the primary endpoint was consistent across the range of LVEF (as a continuous function) in HF without heterogeneity ( p interaction = 0.71). Rates of death, cardiovascular hospitalization, and HF hospitalization each directionally favoured dronedarone versus placebo in HFpEF and HFmrEF, but these treatment effects were not statistically significant in this subgroup. Conclusions Dronedarone is associated with reduced cardiovascular events in patients with paroxysmal or persistent AF/AFL and HF across the spectrum of LVEF, including among those with HFpEF and HFmrEF. These data support a rationale for a future dedicated and powered clinical trial to affirm the net clinical benefit of dronedarone in this population.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".