Response to Letter Regarding Article, “The sPLA <sub>2</sub> Inhibition to Decrease Enzyme Release After Percutaneous Coronary Intervention (SPIDER-PCI) Trial”
Notice bibliographique
Résumé
Coronary Intervention (SPIDER-PCI) Trial"We thank Dr Krijnen and colleagues for their interest in our sPLA 2 Inhibition to Decrease Enzyme Release after Percutaneous Coronary Intervention (SPIDER-PCI) study, the results of which were not suggestive of any evidence of a protective benefit of varespladib, an inhibitor of secretory phospholipase A 2 (sPLA 2 ), in reducing myocardial injury sustained after elective percutaneous coronary intervention (PCI). 1 The hypothesis that varespladib might reduce myocardial injury associated with PCI arose from observations that nonemergent PCI is associated with a marked increase in blood sPLA 2 levels. 2Krijnen et al suggest that our patient cohort was unsuitable for the study of the hypothesis that sPLA 2 is involved in PCI-related cardiac inflammatory injury.We agree, and this was not our hypothesis.Rather, we set out to study whether or not sPLA 2 inhibition would reduce the myocardial injury frequently observed after PCI in a stable elective PCI population.The observational study of Liu et al 2 cited by Krijnen used a cohort that appears to have been similar to ours.Why the inflammatory response was so different from that observed in the SPIDER-PCI study is an interesting and puzzling question.An important clue may lie in the lipid levels of the 2 cohorts.The mean low-density lipoprotein cholesterol in the varespladib group of the SPIDER-PCI cohort was 65 mg/dL.In contrast, the mean low-density lipoprotein cholesterol of the PCI group in the Liu study was 134 mg/dL, and, although the medical therapy of patients in the study is not reported, it is quite likely that dyslipidemia in many of these patients was untreated.Statin therapy, which most our patients were receiving, may have suppressed the pathways that trigger the baseline and the periprocedural release of sPLA 2 and high-sensitivity C-reactive protein, as well.It is noteworthy that the baseline high-sensitivity C-reactive protein levels in our chronically statin-treated patients were closer to those in the Atorvastatin for Reduction of Myocardial Damage During Angioplasty (ARMYDA) patients after 1 week of therapy with atorvastatin 40 mg daily (2.6 mg/L). 3However, troponin I and creatine kinase-MB were still released at levels that were similar to prior observations in stable PCI cohorts.Thus, at least in this group of elective PCI patients on chronic statin therapy, it appears that there is indeed dissociation between the inflammatory axis, as measured by levels of highsensitivity C-reactive protein and sPLA 2 , and the myocardial injury arising from the intervention.Might the results be different if the effect of varespladib on myocardial injury after PCI were to be tested in patients with acute-phase levels of inflammatory markers such as those presenting with an acute coronary syndrome or acute myocardial infarction, as Krijnen et al suggest?The Fewer Recurrent Acute Coronary Events With Near-Term Cardiovascular Inflammation Suppression-ACS (FRANCIS) Trial randomly allocated 625 patients admitted with an acute coronary syndrome, that being a ST-elevation myocardial infarction in Ͼ40% to varespladib 500 mg daily or placebo in addition to atorvastatin 80 mg daily. 4Varespladib treatment resulted in 78.5% reduction in sPLA 2 levels at 16 weeks and a significant but modest reduction in the level of high-sensitivity C-reactive protein beyond that seen with atorvastatin treatment alone after 24 weeks of therapy.There was no signal of clinical event reduction with varespladib treatment, although the study was not powered to detect differences between groups in clinical events.Thus, whether or not varespladib would reduce myocardial injury when administered acutely to patients undergoing PCI in the setting an acute coronary syndrome is unclear, but, we agree, the question is worthy of further study.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,022 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,002 | 0,001 |
| Communication savante | 0,003 | 0,002 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,028 | 0,019 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,019 | 0,017 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».