Abstract Background: With the aim of reducing the risk of Cerebrovascular Accident (CVA) in patients with Non-Valvular Atrial Fibrillation (NVAF), Left Atrial Appendage Occlusion (LAAO) devices are emerging as an alternative to oral anticoagulants. Objective: To analyze the efficacy and safety of the LAAO procedure in patients with NVAF and contraindications and/or failure for oral anticoagulants. Method: The search for evidence was carried out in the electronic databases Medline and Embase till January 2024. Additional searches were conducted on Google Scholar. The clinical trials registry database was also consulted. Two blinded investigators performed the search, study selection, and data collection, and assessed quality and risk of bias using the Cochrane tool for randomized clinical trials. Meta-analyses of eligible trials were performed using RevMan 5.4.1 software. The random effects model was used for all analyses. Results: Five articles were selected, among which three were non-inferiority randomized clinical trials that analyzed the performance and safety of LAAO devices compared to the use of Vitamin K Antagonists (AVKs) or Novel Oral Anticoagulants (NOACs). No randomized clinical trials were found that analyzed populations with absolute contraindications to oral anticoagulants. Having as primary outcomes analyzed the occurrence of stroke (ischemic or hemorrhagic), cardiovascular or unexplained death and systemic embolism, the non-inferiority of the LAAO procedure compared to the use of oral anticoagulants was verified. Conclusions: For patients with an absolute contraindication to anticoagulation and/or failure to use oral anticoagulants, evidence for the use of LAAO devices is scarce. Background CVA (CVA NonValvular Non Valvular NVAF, , (NVAF) (LAAO Objective andor Method 2024 Scholar consulted selection collection Metaanalyses Meta analyses 541 5 4 1 5.4. software Results selected noninferiority non inferiority AVKs (AVKs NOACs. NOACs . (NOACs) ischemic hemorrhagic, hemorrhagic hemorrhagic) embolism verified Conclusions scarce (NVAF 202 54 5.4 (NOACs 20 5. 2

ABSTRACT Objective The aim of this study was to estimate the budget impact of adding cabergoline to the Brazilian Unified Health System (SUS) formulary for the treatment of patients with Cushing’s disease (CD) who do not achieve disease control after transsphenoidal surgery. Materials and methods We conducted a budget impact analysis (BIA) from the perspective of the Brazilian SUS over a 5-year time horizon. We compared two scenarios: ketoconazole (Scenario 1) versus including cabergoline as a treatment option (Scenario 2). All analyses were conducted using Microsoft Excel. Uncertainty was explored in univariate sensitivity analyses. Results The total costs were BRL $25,596,729 for Scenario 1 and BRL $32,469,169 for Scenario 2. The budget impact of adding cabergoline to the formulary for CD treatment within the SUS would be BRL $6,091,036 over 5 years. On univariate analyses, variations in the rates of surgical failure and CD recurrence had the greatest potential to affect the final costs associated with cabergoline. Conclusions The estimated budget impact of adding cabergoline to the formulary for CD treatment within the Brazilian SUS would be about BRL $6 million. While cost savings cannot be expected, the budget impact of adding cabergoline would be lower than that of adding other treatment options for CD. (SUS Cushings Cushing s (CD surgery BIA (BIA 5year year horizon scenarios 2 . 2) Excel 25596729 25 596 729 $25,596,72 32469169 32 469 169 $32,469,16 6091036 6 091 036 $6,091,03 years $ million expected 2559672 59 72 $25,596,7 3246916 3 46 16 $32,469,1 609103 09 03 $6,091,0 255967 7 $25,596, 324691 4 $32,469, 60910 0 $6,091, 25596 $25,596 32469 $32,469 6091 $6,091 2559 $25,59 3246 $32,46 609 $6,09 255 $25,5 324 $32,4 60 $6,0 $25, $32, $6, $25 $32 $2 $3