Abstract 12183: <i>SLCO1B1</i> Genotype-Guided Statin Therapy Lowers LDL Cholesterol in Patients With Statin-Intolerance- A Randomized Controlled Trial
Bibliographic record
Abstract
Introduction: Statin-intolerance is a barrier to reducing cardiovascular disease risk. A genetic variant (*5, rs4149056) in the SLCO1B1 statin hepatic transporter gene is well characterized and linked to higher statin concentrations, statin-intolerance, and statin non-adherence. SLCO1B1*5 has a high negative predictive value for severe simvastatin myopathy; Pravastatin[P]/ fluvastatin[F]/ rosuvastatin[R] are preferred statins in *5 carriers to minimize side effects. The effects of SLCO1B1 genotype-guided statin therapy or delivery of SLCO1B1 genetic risk information are unknown. Hypothesis: Genotype-guided statin therapy (GGST) is superior to usual care in patients with statin-intolerance for statin-related outcomes. Methods: We randomly assigned 159 primary care patients with statin intolerance not prescribed statins to either GGST vs. usual care. GGST patients and their providers received *5 genetic risk information about statin side effects and genotype-specific statin prescription recommendations. Patients in the usual care arm received general information regarding statin risk and prescriptions. The outcomes measured at 3 and 8 months were statin re-initiation, LDL cholesterol (LDLc), and statin adherence using the validated Morisky Medication Adherence Survey. Results: The median age was 64.0 years, 57% were female, 41% reported intolerance to > 1 statin, 75% reported myalgia with statins, and 25% were *5 carriers. Follow up was complete for 144 patients (91%) at 3-months and 118 (74%) at 8-months. At 3-months, GGST was associated with a higher proportion of patients who restarted statin therapy (55.4% vs. 38.0%, p=0.037), and lower LDLc (131.9±42.0 vs. 144.4±43.0, p=0.041), but similar statin adherence scores (p=0.96). Effects at 8-months were consistent with 3-month results for statin prescriptions (54% vs. 37%, p=0.07) and LDLc (128.6±37.9 vs. 141.0±44.4, p=0.07). Use of P/F/R was higher in *5 carriers assigned to GGST versus usual care (92% vs. 67%, p=0.24). Conclusion: In primary care patients with statin-intolerance, SLCO1B1 genotype guided statin therapy is effective in lowering LDLc compared to usual care. GGST, however, did not improve statin adherence in those who re-initiated statin therapy.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.011 | 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".