通过直接药物浓度测量评估急性心肌梗死后高强度他汀类药物的摄入量：PACMAN-AMI试验中与低密度脂蛋白胆固醇反应和冠状动脉斑块改变的关联

Intake of high-intensity statin after acute myocardial infarction assessed by direct drug concentration measurement: association with LDL-C response and coronary plaque modifications in the PACMAN-AMI trial.

作者信息

van der Velpen Vera, Häner Jonas D, Kakizaki Ryota, Bär Sarah, Ueki Yasushi, Siontis George C M, Stortecky Stefan, Biccirè Flavio G, Ambühl Maria, Kaiser Christoph, Iglesias Juan F, Mach Francois, van Geuns Robert J, Daemen Joost, Engstrøm Thomas, Ondracek Anna S, Lang Irene, Bourantas Christos V, Matter Christian M, Windecker Stephan, Koskinas Konstantinos C, Mayr Manuel, Losdat Sylvain, Räber Lorenz, Haschke Manuel, Spirk David

机构信息

Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Bern University Hospital, University of Bern, Freiburgstrasse 15, 3010  Bern, and Institute of Pharmacology, University of Bern, Inselspital, INO-F, Rosenbühlgasse 27, 3010 Bern, Switzerland.

Department of Cardiology, Bern University Hospital, University of Bern, Heart and Vascular Center, Freiburgstrasse 20, Inselspital, 3010 Bern, Switzerland.

出版信息

Eur J Prev Cardiol. 2025 Aug 12. doi: 10.1093/eurjpc/zwaf457.

DOI:10.1093/eurjpc/zwaf457

PMID:40796144

Abstract

BACKGROUND

In real-world settings, adherence to preventive cardiovascular medications is often suboptimal. However, in clinical trials, adherence is crucial for ensuring the validity and generalizability of study results, and their clinical implications.

METHODS AND AIMS

This pre-specified sub-study of the PACMAN-AMI randomized controlled trial investigated the intake of protocol-mandated high-intensity statin background therapy in patients with acute myocardial infarction (AMI), as assessed by direct measurement of rosuvastatin or atorvastatin blood concentrations at 4 and 52 weeks using liquid chromatography tandem mass spectrometry analysis. We evaluated the correlation between statin intake and changes in low-density lipoprotein cholesterol (LDL-C) levels, as well as multi-modality intracoronary imaging endpoints.

RESULTS

Among 300 enrolled patients, four (1.3%) reported statin intolerance within 52 weeks. Of 255 patients with completed imaging follow-up and available blood samples, 3 (1.2%) and 5 (2.0%) had no detectable statin concentrations at 4 and 52 weeks, respectively, and were classified as non-adherent. At 52 weeks, adherent patients demonstrated numerically greater reductions in LDL-C (-2.73 vs. +0.07 mmol/L), intravascular ultrasound-assessed per cent atheroma volume (-1.54% vs. -0.15%), and near-infrared spectroscopy-assessed maximum lipid core burden index (-60.6 vs. 0.0), with a higher increase in optical coherence tomography-assessed fibrous cap thickness (+48.53 vs. +7.98 µm). Sensitivity analysis excluding non-adherent patients confirmed the robustness of the main study results.

CONCLUSION

In the PACMAN-AMI trial, intake of high-intensity statin at 4 and 52 weeks post-AMI was excellent, with minimal statin intolerance. These findings, along with the consistent sensitivity analysis, affirm the validity and reliability of the primary study conclusions.

TRIAL REGISTRATION

ClinicalTrials.gov: NCT03067844.

摘要

背景

在现实环境中，预防性心血管药物的依从性往往欠佳。然而，在临床试验中，依从性对于确保研究结果的有效性、普遍性及其临床意义至关重要。

方法与目的

这项预先设定的PACMAN-AMI随机对照试验的子研究，通过使用液相色谱串联质谱分析法直接测量瑞舒伐他汀或阿托伐他汀在4周和52周时的血药浓度，调查了急性心肌梗死（AMI）患者中方案规定的高强度他汀类药物背景治疗的摄入量。我们评估了他汀类药物摄入量与低密度脂蛋白胆固醇（LDL-C）水平变化以及多模态冠状动脉内成像终点之间的相关性。

结果

在300名入组患者中，4名（1.3%）在52周内报告了他汀类药物不耐受。在255名完成成像随访且有可用血样的患者中，分别有3名（1.2%）和5名（2.0%）在4周和52周时未检测到他汀类药物浓度，被归类为不依从。在52周时，依从性患者在LDL-C降低方面数值上更大（-2.73 vs. +0.07 mmol/L），血管内超声评估的粥样硬化斑块体积百分比降低更多（-1.54% vs. -0.15%），近红外光谱评估的最大脂质核心负担指数降低更多（-60.6 vs. 0.0），光学相干断层扫描评估的纤维帽厚度增加更高（+48.53 vs. +7.98 µm）。排除不依从患者的敏感性分析证实了主要研究结果的稳健性。