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

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