Albliwi, Moath

Abstract Background: Myeloproliferative neoplasms (MPNs) are associated with an elevated risk of thrombotic and hemorrhagic complications. Selective serotonin reuptake inhibitors (SSRIs), commonly prescribed for major depressive disorder and various anxiety disorders, exert a dual effect on platelet function, displaying both prothrombotic and pro hemorrhagic tendencies. However, their impact on vascular outcomes in patients with concomitant MPNs remains unclear. The current study examines the association between SSRI use and the risk of thrombotic and bleeding events in patients with MPNs. Methods: We conducted a retrospective, propensity matched study using the TrinetX network database. Patients >18 years of age, diagnosed with any of the following MPNs: Polycythemia Vera (PV), Essential Thrombocythemia (ET), or Primary Myelofibrosis (PMF) were included. The cohorts were then compared between MPN patients prescribed SSRIs after this diagnosis to those who were never on SSRIs. Patients who were ever prescribed Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) were excluded. Propensity score matching was applied to match demographics and comorbidities. The primary outcomes were all-cause mortality and risk of thrombotic events like deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI). Secondary outcomes were risk of gastrointestinal (GI) bleeding and intracranial hemorrhage (ICH). Results: Propensity score-matching resulted in 10,920 patients in each group, with MPNs, with and without SSRI use respectively. All-cause mortality was higher in those with SSRI use, Hazard Ratio 1.094, (95% CI 1.006, 1.19). The risk of thromboembolism was higher in those with SSRI use: venous thromboembolism, OR 1.968 (1.666, 2.324), PE, OR 2.225 (1.754, 2.824), Stroke OR 3.019 (2.556, 3.566) and MI OR 2.72 (2.288, 3.233). The risk of bleeding was as follows: GI bleeding OR 2.123 (1.877, 2.401) and ICH OR 2.893 (2.268, 3.691). Conclusion: The current study suggests that SSRI use in patients with MPNs is significantly associated with increased risk of thrombosis and bleeding, particularly stroke and ICH. SSRIs predispose to thrombosis by transiently elevating serotonin levels, causing a pro inflammatory state, impaired fibrinolysis, and vascular endothelial dysfunction. However, with chronic use, SSRIs can deplete intraplatelet serotonin levels, impairing platelet aggregation causing an increased risk of bleeding, especially in conjunction with antiplatelet or cytoreductive agent use. Given the high prevalence of SSRI use, our study underscores the need for further prospective studies, heightened clinical vigilance when prescribing SSRIs in patients with MPNs and potential consideration of alternate agents, using individualized treatment strategies.

e19538 Background: Patients with multiple myeloma (MM) and type 2 diabetes mellitus (T2DM) experience increased risks of morbidity and mortality. GLP-1 receptor agonists (GLP-1 RA) offer glycemic and cardiovascular benefits, but their impact on cancer-related outcomes is unclear. This study evaluates the association of GLP-1 RA therapy with clinical outcomes, MM-related biomarkers, and survival in MM patients with T2DM. Methods: We conducted a retrospective cohort analysis using the TriNetX network, including data from 104 healthcare organizations (2014–2019). Two cohorts were defined: (1) MM patients with T2DM starting GLP-1 RA therapy within three months of MM diagnosis and continuing therapy for at least one year (n=1,606 before matching), and (2) MM patients with T2DM not receiving GLP-1 RAs (n=40,306 before matching). Patients included were aged 18 years and older. One-to-one propensity score matching (PSM) balanced systemic MM therapy, BMI, and diabetes medications (e.g., insulin, metformin), yielding 1,279 matched pairs. Outcomes included five-year mortality, ICU and non-ICU hospitalizations, and MM-related biomarkers (hemoglobin, creatinine, neutrophils, and calcium). Most recent lab values were compared in the two groups. Statistical analyses included Kaplan-Meier survival estimates, hazard ratios (HR), risk differences, and T-Test statistics. Results: After PSM, baseline characteristics were well balanced. The mean age was ~ 66 years, white race was ~46%, females were ~ 40%, and hypertension was ~85%. Around 20% of MM patients received autologous transplants and ~27% received lenalidomide in the past. GLP-1 RA therapy was associated with less mortality (HR: 0.44, 95% CI: 0.36–0.54, P < 0.01), ICU admissions (HR: 0.59, 95% CI: 0.50–0.71, P < 0.01), and non-ICU hospitalizations (HR: 0.59, 95% CI: 0.53–0.65, P < 0.01). Patients on GLP-1 RAs had higher hemoglobin levels (11.61 ± 2.30 g/dL vs. 10.75 ± 2.47 g/dL, P < 0.01), with no significant differences in serum creatinine (119.068 µmol/L vs 115.648 µmol/L, P = 0.720) or neutrophils (P = 0.226). Patients who received GLP-1 RAs had higher serum calcium levels (9.17 mg/dL vs. 8.96 mg/dL, P < 0.01). GLP-1 RA use also decreased the incidence of septic shock (HR: 0.53, 95% CI: 0.44–0.64, P < 0.001) and pneumonia (HR: 0.59, 95% CI: 0.49–0.70, P < 0.001). Conclusions: GLP-1 RA therapy improves survival, reduces ICU and non-ICU hospitalizations, and lowers complications in MM patients with T2DM. Biomarker trends over five years suggest potential anticancer effects. Further research should explore whether GLP-1 RAs impact other malignancies, broadening their role in cancer therapy.