Exploratory observational study with Two-Year Outcomes of Early In-Hospital Evolocumab in Acute Coronary Syndrome Patients Undergoing Coronary Artery Bypass Grafting

Giuseppe Nasso^1*Walter Vignaroli¹Giuseppe Santarpino¹Claudio Larosa²Isabella Rosa²Francesco Bartolomucci²Vincenzo Montemurro³Flavio Fiore¹Antongiulio Valenzano¹Giacomo Errico¹Giacomo Schinco¹Mario Siro Brigiani¹Gaetano Contegiacomo¹Vito Margari¹Michele Covelli⁴Alfredo Marchese¹Maria Antonietta De Mola¹Ernesto Greco⁵Giuseppe Speziale¹

• ¹Gruppo Villa Maria SpA, Lugo, Italy
• ²Ospedale Lorenzo Bonomo, Andria, Italy
• ³Azienda Sanitaria Provinciale di Reggio Calabria, Reggio Calabria, Italy
• ⁴Universita LUM Giuseppe Degennaro, Casamassima, Italy
• ⁵Universita Europea di Roma, Rome, Italy

Aims Patients with acute coronary syndrome (ACS) who require coronary artery bypass grafting (CABG) remain at very high ischemic risk due to diffuse native disease and vein graft vulnerability. This study aimed to assess whether very early in-hospital initiation of evolocumab, a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitor, on top of statins improves cholesterol control and mid-term cardiovascular outcomes in this high-risk population. Methods We performed a single-center, retrospective cohort study of 74 ACS patients undergoing isolated CABG (January 2022–July 2023) at Anthea Hospital GVM Care & Research, Bari, Italy. All received high-intensity statin therapy ± ezetimibe (STANDARD, n = 43), while 31 also received evolocumab 140 mg every two weeks (EVOLOCUMAB), initiated pre-angiography, preoperatively, or within 72 hours post-CABG. The primary endpoints were LDL cholesterol (LDL-C) trajectory and attainment of <55 mg/dL at 24 months, and major adverse cardiovascular events (MACE: cardiovascular death, spontaneous myocardial infarction, or any revascularization). Results Seventy-one patients completed 24-month follow-up (EVOLOCUMAB n = 30; STANDARD n = 41). Baseline LDL-C was similar between groups (~156 mg/dL). Evolocumab produced rapid and durable LDL-C reduction: at 24 months, mean LDL-C was 52 ± 11 mg/dL (EVOLOCUMAB) vs 82 ± 18 mg/dL (STANDARD, p<0.001). LDL-C <55 mg/dL was achieved by 73.3% of EVOLOCUMAB vs 29.3% of STANDARD patients (p<0.001). MACE occurred in 10.0% (EVOLOCUMAB) vs 24.4% (STANDARD), with lower risk in EVOLOCUMAB (HR 0.48, 95% CI 0.22–0.94; p = 0.035), mainly due to fewer repeat revascularizations. Evolocumab was well tolerated; no discontinuations due to adverse events were observed Conclusion In ACS patients undergoing CABG, very-early in-hospital evolocumab plus statins achieved sustained LDL-C lowering and fewer adverse cardiovascular events over two years. Given the retrospective observational design, causal inference is limited and residual confounding cannot be excluded. These findings are hypothesis-generating and require confirmation in randomized trials.