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.
Plain language summary : Statins are essential medications after a heart attack, helping to lower levels of harmful LDL cholesterol, slow the progression of atherosclerosis, and reduce the risk of future cardiovascular events. In clinical trials, it is crucial that participants take their prescribed therapies consistently to ensure the reliability and relevance of the study results. This analysis from the PACMAN-AMI trial evaluated how well patients adhered to high-intensity statin therapy during the first year after a heart attack. Statin use was assessed by measuring drug levels in the blood. The findings were reassuring: almost all patients were taking their medication as prescribed, and side effects were very rare. Patients who were adherent showed greater reductions in LDL cholesterol and more favourable changes in coronary artery structure, as assessed by advanced intracoronary imaging techniques. These findings strengthen the validity of the PACMAN-AMI trial’s primary conclusions, published in JAMA. Measuring statin levels in the blood may help identify patients who appear not to respond to treatment, even though they are supposedly taking intensive cholesterol-lowering therapy.© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.
