Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery

Abstract

Background For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. Methods The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. Discussion Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. Trial registration ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Prehospital tranexamic acid for trauma victims

“…More recently, the Perioperative Ischemic Evaluation-3 (POISE-3) trial randomly assigned 9535 adults at risk of bleeding and cardiovascular complications undergoing non-cardiac surgery to tranexamic acid or matching placebo in 2022. There was no evidence of any increased risk of vascular occlusive events (occurring in 14.2% of patients in the tranexamic acid group and 13.9% in the placebo group (hazard risk [HR] = 1.02; 95% CI, 0.92–1.14)) and TXA reduced the risk of major bleeding by approximately 25% (hazard risk [HR] = 0.75; 95% CI, 0.65–0.87) [ 6 , 7 ]. Widespread use of TXA would improve surgical safety, avoid unnecessary blood use, reduce the risk of infections from blood transfusions and save healthcare costs [ 8 ].…”

Bleeding and Tranexamic Acid in Patients Undergoing Noncardiac Surgery

“…5 However, beyond these particular scenarios, it was unknown whether tranexamic acid had a role in the general surgical population in preventing operative bleeding. 6 In particular, an unknown risk of administering tranexamic acid in the general surgical population for noncardiac surgery could be an increase in vascular thromboses. 4 A recent metaanalysis of 234 studies with 102,681 patients examined the effect of tranexamic acid on thrombotic events in bleeding patients.…”

“…The inclusion criteria focused on patients 45 years with cardiovascular disease undergoing noncardiac surgery. 6 This patient cohort was susceptible to cardiovascular complications in the perioperative period, including myocardial injury after noncardiac surgery (MINS). The hemodynamic and hematologic challenges of bleeding during noncardiac surgery can be detrimental in this vulnerable group and are associated independently with 30-day mortality.…”

A angiotomografia de artérias coronárias na estratificação do risco cardiovascular em pacientes com câncer submetidos à cirurgia de alto risco

“…A hipotensão pode ser um dos fatores responsáveis pelo desbalanço entre oferta e demanda de oxigênio e está associada a injúria miocárdica e infarto no pós-operatório 19,57 Há um estudo em andamento, o estudo POISE-3 (PeriOperative Ischemic Evaluation-3), que tem como objetivo avaliar o efeito de uma estratégia de prevenção de hipotensão versus uma estratégia de prevenção de hipertensão no risco de eventos cardiovasculares maiores, em cirurgias não cardíacas 59 .…”

“…Foram feitas análises da ocorrência de injúria miocárdica em relação aos dados basais e demográficos dos pacientes. Foi observado que a injúria miocárdica ocorreu com maior frequência nos pacientes com idade elevada (grupo MINS 69 [64][65][66][67][68][69][70][71][72][73][74] anos versus grupo sem MINS 64 [59][60][61][62][63][64][65][66][67][68][69][70] A análise de ocorrência de eventos combinados com relação as variáveis intraoperatórias mostram que houve uma maior chance de eventos combinados em pacientes que apresentaram maior porcentual de tempo de hipotensão no intraoperatório, (grupo sem eventos 13% [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] versus 14% [8][9][10][11]…”