Body mass index from the RE-LY trial: further evidence of the obesity paradox
Bibliographic record
Abstract
Abstract Background The obesity paradox has been reported in 3 post-hoc analyses evaluating the direct oral anticoagulants (DOAC) against warfarin (W): apixaban (ARISTOTLE), rivaroxaban (ROCKET), and edoxaban (ENGAGE-AF). Purpose To evaluate the obesity paradox in a post-hoc analysis of the RE-LY trial, comparing dabigatran 110 mg BID (D110), 150 mg BID (D150), and W by body mass index (BMI). Methods Baseline characteristics were evaluated using World Health Organization (WHO) criteria of overweight and obese (BMI ≥25 kg/m2) and under and normal weight (BMI <25 kg/m2). Stroke and systemic embolism, ischemic stroke, major bleeding, mortality, and intracranial hemorrhage were evaluated using BMI as a continuous variable and by the WHO criteria using a cox proportional hazard model. Results BMI was available in 99.9% of patients randomized; 74% had a BMI ≥25. At baseline, patients with a BMI ≥25 were younger (70.9 vs 73.1, p<0.001) and had fewer prior strokes (11.5% vs 15.6%, p<0.001), but higher mean creatinine clearance (78.3 vs 57.0, p<0.001) and rates of diabetes (25.8% vs 16.1%, p<0.001) (Table 1). Independent of drug assignment, patients with a BMI ≥25 had lower rates of stroke and systemic embolism (HR 0.65 [95% CI 0.54–0.79], p<0.001), ischemic stroke (0.75 [95% CI 0.60, 0.94], p=0.01), major bleeding (HR 0.79 [95% CI 0.69,0.89], p<0.001), mortality (HR 0.60 [95% CI 0.53, 0.67], p<0.001) and intracranial hemorrhage (HR 0.53 [95% CI 0.38, 0.73], p<0.001) compared to those with a BMI <25. Using BMI as a continuous variable combining all outcomes at 3 years, endpoint rates declined as BMI approached 25 in all 3 treatment groups. The exceptions were intracranial hemorrhage for D110 and D150 and stroke in D150 patients, where rates were low independent of BMI. No significant interaction between BMI and treatment was observed in individual outcomes except for the D110 vs. D150 comparison for major bleeding, in favor of D110 for patients with BMI ≥25 (HR 0.77 [95% CI 0.65, 0.91] and HR 1.12 [95% CI 0.86, 1.47], interaction p=0.0190). Conclusions In RE-LY, independent of drug assignment, patients with a higher BMI had improved outcomes, demonstrating the obesity paradox. As BMI increased towards 25, outcome rates improved except for intracranial hemorrhage rates for both D110 and D150 and ischemic stroke rates for D150, which were low independent of BMI. Patients treated with D110 with a BMI ≥25 kg/m2 had significantly lower rates of bleeding compared to D150. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Sharpe Strumia Foundation
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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 | 0.014 | 0.014 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".