New findings reveal that early administration of ezetimibe with statins following a myocardial infarction (MI) significantly reduces the risk of future cardiovascular events when compared with delayed use or statin monotherapy. The study found that out of the 35,826 patients enrolled, the one-year incidence of Major Adverse Cardiovascular Events (MACE) was 1.79 in the 16.9% of patients receiving ezetimibe within 12 weeks, and 2.58 in the 18.1% receiving it 13 weeks to 16 months post-discharge. The majority (65%), who did not receive ezetimibe at all recorded a one-year MACE incidence of 4.03 per 100 patient-years, said the paper’s authors, who were led by Margret Leosdottir, MD, PhD, from Skåne University Hospital in Malmö, Sweden. Combination therapy “MI care pathways should implement early combination therapy with statins and ezetimibe as standard care, because delaying use of combination LLT or using high-intensity statin monotherapy is associated with avoidable harm,” the team said. Further findings revealed that delaying ezetimibe addition led to worse outcomes, with the 3-year hazard ratio for MACE being 1.14 for late initiation and 1.29 for no initiation compared with early combination therapy. For cardiovascular death alone, hazard ratios were 1.64 (late) and 1.83 (none). In her concluding comments, the authors emphasized the urgency of changing care protocols suggesting that the price of delay was high and one that patients could no longer afford to pay. Clara K. Chow, MBBS, PhD, and Oliver Archer, MD, from University of Sydney, Westmead Hospital in New South Wales, Australia, and Leonard Kritharides, MBBS, PhD, from Sydney Medical School at the University of Sydney endorsed the study’s findings, saying that early ezetimibe-statin combination therapy should become the standard of care for post-MI patients. SWEDEHEART and RACING In their accompanying editorial comment, the commentators cited its potential to reduce therapeutic inertia and improve adherence, hailing real-world evidence from the SWEDEHEART trial as pivotal. The editorial also highlighted the non-inferiority of moderate-intensity statin-ezetimibe therapy compared to high-dose statins alone, based on trials like RACING. However, the authors cautioned that registry data could reflect selection bias, as physicians may prioritize combination therapy for more adherent patients, a factor that could skew outcomes. Despite this, they deemed early initiation "reasonable and pragmatic," urging a shift from stepwise approaches. Study methodology The study used a trial emulation approach called the clone-censor-weight method to simulate a randomized controlled trial using real-world registry data. In total, 35,826 patients were included, of whom 6,040 (16.9%) received ezetimibe combination therapy early, 6,495 (18.1%) received ezetimibe combination therapy late, and 23,291 (65.0%) did not receive ezetimibe during the first 16 months after discharge. The median age at the index MI was 65.1 years (Q1-Q3: 57.0-72.1 years), and 26.0% were women. The primary endpoint of the study was major adverse cardiovascular events (MACE), consisting of all-cause death, nonfatal MI and nonfatal stroke. Sources: Leosdottir M, Schubert J, Brandts J, et al. Early Ezetimibe Initiation After Myocardial Infarction Protects Against Later Cardiovascular Outcomes in the SWEDEHEART Registry. JACC 2025; 85; 1550–1564. Chow CK, Archer O, Kritharides L. Should Patients With Myocardial Infarction Be Started on Combination Therapy With Ezetimibe Before Hospital Discharge? JACC 2025; 85; 1565–1567. Image Credit: dragonstock – stock.adobe.com