The Impact of Exacerbation History on the Safety and Efficacy of Aclidinium in Patients with Chronic Obstructive Pulmonary Disease and Increased Cardiovascular Risk: ASCENT-COPD Trial
Bibliographic record
Abstract
Purpose: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased risk of major adverse cardiovascular events (MACE) and mortality. Here, we investigate whether the safety and efficacy of aclidinium bromide differ due to exacerbation history in patients with COPD and increased cardiovascular risk. Patients and Methods: ASCENT-COPD was a Phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group study of patients with moderate-to-very severe COPD and increased cardiovascular risk. Patients were randomized 1:1 to receive aclidinium or placebo twice daily for up to 3 years. Outcomes included time to first MACE and all-cause mortality over 3 years, exacerbation rate during the first year on-treatment, and change in baseline pre-dose forced expiratory volume in 1 second (FEV 1 ) over 3 years. This pre-specified subgroup analysis compared outcomes in patients receiving aclidinium vs placebo. The comparison of patients with vs without an exacerbation history was added following a protocol amendment to increase enrollment in the primary study. Results: Of 3589 patients, 2156 (60.1%) had ≥ 1 moderate or severe exacerbations in the prior year, compared with 1433 (39.9%) without prior exacerbations. Although patients with an exacerbation history had numerically higher rates of MACE and mortality regardless of treatment, aclidinium did not increase risk of MACE (≥ 1: hazard ratio [HR] 0.79, 95% confidence interval [CI]: 0.54– 1.16; none: HR 1.27, 95% CI: 0.65– 2.47; interaction P =0.233) or all-cause mortality (≥ 1: HR 1.08, 95% CI: 0.81– 1.43; none: HR 0.66, 95% CI: 0.36– 1.22; interaction P =0.154), regardless of exacerbation history. Aclidinium reduced the exacerbation rate vs placebo irrespective of exacerbation history (≥ 1: rate ratio [RR] 0.80, 95% CI: 0.68– 0.94; none: RR 0.69, 95% CI: 0.54– 0.89; interaction P =0.340) and improved FEV 1 (interaction P =0.633). Conclusion: In patients with moderate-to-very severe COPD and increased cardiovascular risk, aclidinium did not increase risk of MACE or mortality and reduced exacerbation rate vs placebo, regardless of exacerbation history. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01966107. Keywords: COPD, COPD exacerbation, aclidinium, MACE, mortality
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".