Major adverse cardiovascular events (MACE) in cancer patients treated with tirzepatide compared to GLP-1 receptor agonists: A target trial emulation using real-world data.

12027 Background: Cardiovascular disease (CVD) is a leading cause mortality in cancer patients. Obesity and type 2 diabetes are well-known modifiable risk factors for CVD progression and adverse CV related outcomes. We aim to assess the CV benefit of tirzepatide versus GLP-1 receptor agonists (GLP-1RA), a mainstay treatment in management of obesity and cardiometabolic disease, in cancer patients. Methods: We conducted a target trial emulation using TriNetX, an aggregated EHR platform. We identified adults (May 2022-Jan 2024) diagnosed with solid neoplasm and cardiometabolic conditions (hypertension, dyslipidemia, obesity, or type 2 diabetes). We excluded patients with in situ neoplasms, hematologic malignancy, metastatic solid neoplasm, medication contraindication (type 1 diabetes, gastroparesis, thyroid cancer), performance status ECOG > 3, or on dialysis. Patients were divided into two exclusive groups: tirzepatide or GLP-1RA. The first prescription of each medication was defined as time zero/index event. Individuals with any MACE within 60 days prior to index event were excluded. Study groups were propensity matched, using a 1:1 nearest neighbor algorithm, for 55 covariates: demographics, Charlson comorbidity index and cardiac conditions, chemotherapy, radiation, BMI, HbA1c, LDL, eGFR, systolic BP, medications, smoking/alcohol, and social determinants. Primary outcome was incidence of MACE (acute myocardial infarction, stroke, or CV death) and overall survival over a 2-year period. Secondary outcomes were changes in HbA1c and BMI. Kaplan Meier analysis and hazard ratios (HRs) were calculated to compare time-to-event outcomes. Results: We identified 42,584 patients [mean age 55.4 (±12.1) years; 62.5% female; 63.1% White; mean HbA1c 6.82 (±1.81); mean BMI 37.5 (±7.7)] with solid tumors and cardiometabolic conditions. Tirzepatide was associated with a significant MACE reduction compared to GLP-1RA and improved overall survival (Table 1). At follow-up, mean HbA1c was significantly lower in tirzepatide group (6.21 ± 1.28) compared to GLP-1RA (6.50 ± 1.46; p < 0.001). Patients on tirzepatide also experienced greater BMI reduction (34.7 ± 7.7 kg/m2) compared to GLP-1RA (35.5 ± 7.7 kg/m2; p < 0.001). Conclusions: Tirzepatide was associated with significant reductions in MACE, HbA1c, and BMI compared to GLP-1RA, suggesting a preferential pharmacotherapy option for addressing obesity and cardiovascular disease reduction in cancer patients while improving overall survival outcomes and quality of care in this high-risk population. Outcome Adjusted HR (95% CI) p- value MACE 0.761 (0.616-0.940) 0.011 Myocardial Infarction 0.650 (0.475-0.889) 0.007 Stroke 1.103 (0.937-1.300) 0.240 Ischemic Heart Disease 0.785 (0.627-0.983) 0.035 Cardiac Death 0.621 (0.365-0.890) 0.032 Overall Survival 0.563 (0.415-0.736) <0.001