Atorvastatin and Aortic Stiffness During Anthracycline-Based Chemotherapy
Bibliographic record
Abstract
Importance: Anthracyclines, which are key to many chemotherapeutic protocols, have been associated with increased vascular stiffness, a major factor associated with cardiovascular morbidity and mortality. There is no evidence-based intervention to prevent anthracycline-associated vascular dysfunction. Objective: To investigate whether atorvastatin pretreatment is associated with attenuation of the anthracycline-induced increase in aortic stiffness. Design, Setting, and Participants: This study is a secondary analysis of a double-blind, randomized clinical trial (Statins to Prevent the Cardiotoxicity From Anthracyclines [STOP-CA]). Enrollment occurred between January 25, 2017, and September 10, 2021, with the last follow-up on October 10, 2022. Primary analyses were reported on August 8, 2023. STOP-CA was a multicenter trial across 9 academic centers in the US and Canada. Participants were patients with newly diagnosed lymphoma scheduled to undergo anthracycline-based chemotherapy with no clinical indication for a statin. Intervention: Atorvastatin (40 mg, once daily) or placebo for 12 months. Main Outcomes and Measures: This subanalysis of the STOP-CA trial includes post hoc end points with cardiac magnetic resonance imaging-derived aortic arch pulse wave velocity (PWV) and aortic distensibility (AD). An intention-to-treat approach was applied. The proportions of participants with a 1 SD or more increase in PWV and a 1 SD or more decrease in ascending aortic distensibility (AAD) were calculated in each group over 12 months. An increase in PWV of 0.15 m per second or more, a previously defined annual rate in individuals of similar age, was also assessed as a secondary end point. Results: Of the 300 participants (150 randomized to atorvastatin and 150 randomized to placebo), 152 (mean [SD] age, 51 [17] years; 72 female [47%]; 82 treated with atorvastatin) had paired PWV data, and 168 had paired AD data. The PWV values remained similar in the atorvastatin group (mean [SD], 6.5 [1.9] vs 6.5 [2.0] m per second) but increased in the placebo group (5.7 [1.8] vs 6.8 [2.0] m per second) over 12 months. A 1 SD or more increase (0.8 m per second) in PWV was observed among 4 of 82 patients (5%) with atorvastatin and 35 of 70 patients (50%) with placebo (odds ratio, 0.05; 95% CI, 0.02 to 0.16; P < .001) at 12 months. A 1 SD or more decrease (1.8 × 10-3 mm Hg-1) in AAD was observed among 6 of 88 patients (7%) with atorvastatin and in 14 of 80 patients (18%) with placebo. A 1 SD or more increase in PWV was associated with a mean left ventricular ejection fraction decline of 2.70% (95% CI, -4.65% to -0.81%; P = .006). Conclusions and Relevance: Pretreatment with atorvastatin was associated with preservation of vascular function among patients with lymphoma undergoing anthracycline-based chemotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02943590.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".