Pharmacology and clinical assessment of cariporide for the treatment coronary artery diseases
Bibliographic record
Abstract
Myocardial protection through pharmacological approaches represents a large therapeutic challenge and is an important therapeutic strategy in patients with coronary artery disease, particularly after myocardial infarction. Extensive animal experiments have repeatedly demonstrated the efficacy of sodium-hydrogen exchange (NHE) inhibition as a potent cardioprotective approach. The heart possesses primarily the NHE1 isoform which has led to the development of NHE1 specific inhibitors for cardiovascular therapeutics. Cariporide (HOE 642) is the first of such agents to have been developed and subjected to clinical trial. Preclinical studies with cariporide revealed excellent protection against necrosis, apoptosis, arrhythmias and mechanical dysfunction in hearts subjected to ischaemia and reperfusion. Cariporide has recently been evaluated in a large dose-finding Phase II/Phase III clinical trial (GUARDIAN) to assess its efficacy in patients with acute coronary syndromes. Overall results failed to demonstrate protection but sub-group analysis revealed significant risk reductions with the highest cariporide dose (120 mg t.i.d.) especially in high risk patients undergoing coronary artery bypass surgery. This suggests that insufficient dosage may have accounted, at least in part, for the less than optimum results. Another NHE1 inhibitor, eniporide, is currently in Phase II clinical trial (ESCAMI) in patients with acute myocardial infarction (MI) who are given angioplasty or thrombolysis. Although the study has not been completed interim findings appear positive. Both drugs were well-tolerated and produced no excess side effects compared with placebo. Further studies are needed to confirm the efficacy of NHE1 inhibitors for the treatment of coronary heart disease, even so initial results are encouraging.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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".