Off-pump versus on-pump coronary artery bypass grafting in frail patients: study protocol for the fragile multicenter randomized controlled trial

Abstract Introduction: Advances in modern medicine have led to people living longer and healthier lives. Frailty is an emerging concept in medicine yet to be explored as a risk factor in cardiac surgery. When it comes to CABG surgery, randomized controlled clinical trials have primarily focused on low-risk (ROOBY, CORONARY), elevated-risk (GOPCABE) or high-risk patients (BBS), but not on frail patients. Therefore, we believe that off-pump CABG could be an important technique in patients with limited functional capacity to respond to surgical stress. In this study, the authors introduce the new national, multicenter, randomized, controlled trial "FRAGILE", to be developed in the main cardiac surgery centers of Brazil, to clarify the potential benefit of off-pump CABG in frail patients. Methods: FRAGILE is a two-arm, parallel-group, multicentre, individually randomized (1:1) controlled trial which will enroll 630 patients with blinded outcome assessment (at 30 days, 6 months, 1 year, 2 years and 3 years), which aims to compare adverse cardiac and cerebrovascular events after off-pump versus on-pump CABG in pre-frail and frail patients. Primary outcomes will be all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and coronary reintervention. Secondary outcomes will be major adverse cardiac and cerebrovascular events, operative time, mechanical ventilation time, hyperdynamic shock, new onset of atrial fibrillation, renal replacement therapy, reoperation for bleeding, pneumonia, length of stay in intensive care unit, length of stay in hospital, number of units of blood transfused, graft patency, rate of complete revascularization, neurobehavioral outcomes after cardiac surgery, quality of life after cardiac surgery and costs. Discussion: FRAGILE trial will determine whether off-pump CABG is superior to conventional on-pump CABG in the surgical treatment of pre-frail and frail patients. Trial registration: ClinicalTrials.gov, ID: NCT02338947. Registered on August 29th 2014; last updated on March 21st 2016.

Fondaparinux versus Enoxaparin - Which is the Best Anticoagulant for Acute Coronary Syndrome? - Brazilian Registry Data / Fondaparinux versus Enoxaparina - Qual o Melhor Anticoagulante para Síndrome Coronariana Aguda? - Dados de um Registro Brasileiro

Abstract Background: Recent studies have shown fondaparinux's superiority over enoxaparin in patients with non-ST elevation acute coronary syndrome (ACS), especially in relation to bleeding reduction. The description of this finding in a Brazilian registry has not yet been documented. Objective: To compare fondaparinux versus enoxaparin in in-hospital prognosis of non-ST elevation ACS. Methods: Multicenter retrospective observational study. A total of 2,282 patients were included (335 in the fondaparinux group, and 1,947 in the enoxaparin group) between May 2010 and May 2015. Demographic, medication intake and chosen coronary treatment data were obtained. Primary outcome was mortality from all causes. Secondary outcome was combined events (cardiogenic shock, reinfarction, death, stroke and bleeding). Comparison between the groups were done through Chi-Square test and T test. Multivariate analysis was done through logistic regression, with significance values defined as p < 0.05. Results: With regards to treatment, we observed the performance of a percutaneous coronary intervention in 40.2% in the fondaparinux group, and in 35.1% in the enoxaparin group (p = 0.13). In the multivariate analysis, we observed significant differences between fondaparinux and enoxaparin groups in relation to combined events (13.8% vs. 22%. OR = 2.93, p = 0.007) and bleeding (2.3% vs. 5.2%, OR = 4.55, p = 0.037), respectively. Conclusion: Similarly to recently published data in international literature, fondaparinux proved superior to enoxaparin for the Brazilian population, with significant reduction of combined events and bleeding.

Resumo Fundamento: Estudos recentes têm apresentado superioridade do fondaparinux em relação à enoxaparina em pacientes com síndrome coronariana aguda (SCA) sem supradesnivelamento de ST, principalmente relacionada à redução de sangramentos. A descrição desse achado em registro brasileiro ainda não foi documentada. Objetivo: Comparar fondaparinux versus enoxaparina no prognóstico intrahospitalar em SCA sem supradesnivelamento de ST. Métodos: Estudo retrospectivo, multicêntrico e observacional. Foram incluídos 2.282 pacientes (335 no grupo fondaparinux e 1.947 no grupo enoxaparina) entre maio de 2.010 e maio de 2.015. Foram obtidos dados demográficos, medicações utilizadas e tratamento coronariano adotado. O desfecho primário foi mortalidade por todas as causas. O desfecho secundário foi eventos combinados (choque cardiogênico, reinfarto, morte, acidente vascular cerebral e sangramentos). A comparação entre os grupos foi realizada por meio de Q-quadrado e teste-T. A análise multivariada foi realizada por regressão logística, sendo considerado significativo p < 0,05. Resultados: Em relação ao tratamento, observou-se realização de intervenção coronária percutânea em 40,2% no grupo fondaparinux e 35,1% no grupo enoxaparina (p = 0,13). Na análise multivariada, observaram-se diferenças significativas entre os grupos fondaparinux e enoxaparina em relação a eventos combinados (13,8% vs. 22%, OR = 2,93, p = 0,007) e sangramentos (2,3% vs. 5,2%, OR = 4,55, p = 0,037), respectivamente. Conclusão: Semelhante aos dados recentemente publicados na literatura mundial, fondaparinux mostrou-se superior à enoxaparina para a população brasileira, com redução significativa de eventos combinados e sangramentos.