Fig. 3: Metoprolol-induced cardioprotection in patients undergoing STEMI shows time-of-day variations.

A METOCARD-CNIC trial timeline for the full study population of 220 patients (112 control, 108 metoprolol). B Time-of-day of ST-segment elevation myocardial infarction (STEMI) onset in the full METOCARD-CNIC study population and in patients with pre-percutaneous coronary intervention (PCI) TIMI grade 0–1 (178 patients: 92 control, 86 metoprolol). Patients were assessed for infarct size (IS) by cardiac magnetic resonance (CMR) imaging 1 week after acute myocardial infarction as per the standard METOCARD protocol. C–E CMR analysis of cardiac anatomy and function at 1-week post-reperfusion stratified by time of STEMI onset in all patients (left) and in patients with pre-PCI TIMI grade 0–1 (right). Linear regression models were used to evaluate the association between time-of-day of myocardial infarction and IS (necrotic tissue, g) (C); microvascular obstruction (MVO, % of left ventricle) (D); and left ventricular ejection fraction (LVEF, %) (E), after adjusting for the following cofounders: sex, age, diabetes mellitus, ischemia duration, and pre-PCI TIMI. Patient numbers (C | M) = P1, 21 | 17; P2, 39 | 32; P3, 28 | 33; and P4, 24 | 26 for the full cohort and P1, 18 | 14; P2, 30 | 25; P3, 23 | 27; and P4, 21 | 21 for patients with pre-PCI TIMI grade 0 to 1. Data are presented as mean ± SD. Differences were deemed statistically significant at P < 0.05. C control group, M metoprolol group, CK creatine kinase. Period 1 (P1), from midnight to 6 am; period 2 (P2), from 6 am to noon; period 3 (P3), from noon to 6 pm; and period 4 (P4), from 6 pm to midnight. Source data are provided as a Source Data file.