Effect of bempedoic acid on uric acid and gout in 3621 patients with hypercholesterolemia: pooled analyses from phase 3 trials
Bibliographic record
Abstract
Abstract Background Bempedoic acid (BA), an oral ATP-citrate lyase inhibitor, significantly lowers low-density lipoprotein cholesterol levels in patients with hypercholesterolemia. In clinical trials of BA, small mean increases in uric acid have been reported. BA weakly inhibits organic anion transporter 2 (OAT2) in vitro, which may account for small elevations in serum uric acid. Purpose To assess uric acid levels and incidence of gout with BA treatment. Methods Data were pooled from 4 randomized (2:1), double-blind studies of BA (180 mg daily) vs placebo for 12 weeks to 52 weeks in patients with hypercholesterolemia on stable background lipid-lowering therapy. Safety assessments included adverse events of special interest (elevation in uric acid levels, gout) and laboratory assessments. Results A total of 2424 patients treated with BA and 1197 patients on placebo were included in this analysis. Mean (SD) baseline uric acid levels were 6.0 (1.4) mg/dL for both groups. History of gout was reported by 5.2% (127/2424) and 5.8% (69/1197) in the BA and placebo groups, respectively. At week 12, mean (SD) serum uric acid levels (% change from baseline) increased from baseline with BA treatment by 0.82 (0.97) mg/dL (14.8%) vs –0.02 (0.82) mg/dL (0.67%) for placebo. Elevations in serum uric acid levels typically occurred within the first 4 weeks of treatment, remained stable during treatment, and returned to baseline after treatment discontinuation. Gout was reported in 1.4% (BA) and 0.4% (placebo) of patients, and hyperuricemia was reported in 1.7% (BA) and 0.6% (placebo) of patients. Other potential clinical consequences of elevated uric acid levels (eg, events associated with nephrolithiasis), were similar between groups (0.7% vs 0.8%). In both groups, patients who reported gout during the studies were more likely to have a medical history of gout or elevated baseline uric acid levels (Table). Few patients discontinued treatment due to gout (n=1, <0.1% [BA]) or uric acid increases (n=2, <0.1% [BA]). Conclusion Mean increases in uric acid levels were small, remained stable while patients continued to receive treatment, were infrequently associated with AEs, and were reversible on discontinuation of BA Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Esperion Therapeutics funded the research for this study and provided writing support for this abstract. Medical writing assistance was provided by Agnella Izzo Matic, PhD, CMPP, and Kelly M Cameron, PhD, CMPP, of JB Ashtin.
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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 | 0.009 | 0.010 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.015 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".