Percent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents
Bibliographic record
Abstract
AIMS: Current statin guidelines in Europe and Canada advocate achieving a fixed LDL target or the attainment of a ≥50% reduction in low-density lipoprotein cholesterol (LDLC), while current US guidelines advocate the use of statin therapies that reduce LDLC by <50% (moderate intensity) or ≥50% (high intensity). Data are limited, however, linking the achievement of these % reduction thresholds to subsequent cardiovascular outcomes particularly for contemporary high-intensity regimens. METHODS AND RESULTS: In a randomized trial of 17 082 initially healthy men and women with median baseline LDLC of 108 mg/dL (interquartile range 94-119), we (i) used waterfall plots to assess the variability in LDLC response to rosuvastatin 20 mg daily and (ii) evaluated the impact of reaching ≥50% reductions in LDLC on risk of developing the first cardiovascular events. Among rosuvastatin allocated participants, 3640 individuals (46.3%) experienced an LDLC reduction ≥50%; 3365 individuals (42.8%) experienced an LDLC reduction >0 but <50%; and 851 individuals (10.8%) experienced no reduction or an increase in LDLC compared with baseline. These % LDLC reductions directly related to the risks of first cardiovascular events; at trial completion, incidence rates for the primary endpoint were 11.2, 9.2, 6.7, and 4.8 per 1000 person-years for those in the placebo, no LDLC reduction, LDLC reduction <50%, and LDLC reduction ≥50% groups, respectively. Compared with placebo, the multivariable adjusted hazard ratios for sequentially greater on-treatment per cent reductions in LDLC were 0.91 (95%CI 0.54-1.53), 0.61 (95%CI 0.44-0.83), and 0.43 (95%CI 0.30-0.60) (P < 0.00001). Similar relationships between % reduction and clinical outcomes were observed in analyses focusing on non-HDLC or apolipoprotein B. CONCLUSIONS: As documented for low- and moderate-intensity regimens, variability in % LDLC reduction following high-intensity statin therapy is wide yet the magnitude of this % reduction directly relates to efficacy. These data support guideline approaches that incorporate % reduction targets for statin therapy as well as absolute targets, and might provide a structure for the allocation of emerging adjunctive lipid-lowering therapies such as PCSK9 inhibitors should these agents prove broadly effective for cardiovascular event reduction.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.000 |
| 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".