Proprotein convertase subtilisin/kexin type 9 inhibitors for reduction of cardiovascular events
Bibliographic record
Abstract
PURPOSE: The efficacy, safety, and place in therapy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for lipid lowering are reviewed. SUMMARY: PCSK9 inhibitors are injectable monoclonal antibodies that increase the availability of low-density lipoprotein (LDL) receptors, resulting in a reduction in serum LDL cholesterol (LDL-C). The currently available PCSK9 inhibitors alirocumab and evolocumab were shown to reduce LDL-C concentrations by approximately 55-60% relative to placebo use when used as monotherapy or added to other lipid-lowering therapies. A large randomized controlled trial of evolocumab demonstrated a reduction in cardiovascular events that translated to a 16% relative risk reduction per 1-mmol/L (39-mg/dL) reduction in LDL-C over 2 years, nearly identical to risk reductions reported with use of statins for LDL-C lowering. Another large outcome trial with alirocumab is ongoing. PCSK9 inhibitors are well tolerated, and minor injection-site reaction is the only known adverse effect. Routine use of these agents in all patients with cardiovascular disease is not cost-effective at the current annual cost of therapy of approximately $14,000 in the United States and $7,000 in other Western countries. Careful patient selection may increase the benefit-to-cost ratio of these agents. CONCLUSION: The PCSK9 inhibitors alirocumab and evolocumab, as adjuncts to oral lipid-lowering agents or as monotherapy, lower serum LDL-C concentrations and reduce the risk of cardiovascular events. These agents are safe and well tolerated, but high cost and lack of cost-effectiveness limit their routine use.
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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 | 0.008 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.008 | 0.005 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".