Dataset Information

Tranexamic acid and rosuvastatin in patients at risk of cardiovascular events after noncardiac surgery: a pilot of the POISE-3 randomized controlled trial.

ABSTRACT:

Background

Surgical bleeding is associated with postoperative cardiovascular complications. The efficacy and safety of tranexamic acid (TXA) in noncardiac surgery are still uncertain. Statins may prevent perioperative cardiovascular complications. We conducted a pilot to assess the feasibility of a perioperative trial of TXA and rosuvastatin.

Methods

Using a factorial design, we randomized patients at cardiovascular risk undergoing noncardiac surgery to intravenous TXA (1 g at the start and end of surgery) or placebo, and oral rosuvastatin (40 mg before and 20 mg daily for 30 days after surgery) or placebo. Feasibility outcomes included recruitment rates, follow-up, and compliance to interventions. Clinical outcomes were secondarily explored.

Results

After 3 months, we changed the design to a partial factorial due to the difficult recruitment of statin-naive patients. Over 6 months, 100 patients were randomized in the TXA trial (49 TXA, 51 placebo), 34 in the rosuvastatin trial (18 rosuvastatin, 16 placebo). Ninety-two percent (95% CI 80-98) of TXA and 86% (95% CI 74-94) of TXA-placebo patients received the 2 study doses. Thirty-three percent (95% CI 13-59) of rosuvastatin patients and 37% (95% CI 15-65) of rosuvastatin-placebo patients discontinued the study drug. A major cardiovascular complication occurred at 30 days in 1 TXA and 6 TXA-placebo patients, and 1 rosuvastatin and no rosuvastatin-placebo patients.

Conclusions

Our pilot study supports the feasibility of a perioperative TXA trial in noncardiac surgery. Feasibility of a perioperative rosuvastatin trial is uncertain because of a high prevalence of statin use in the target population and concerns about compliance.

Trial registration

ClinicalTrials.govNCT02546648.

SUBMITTER: Marcucci M

PROVIDER: S-EPMC7372857 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Tranexamic acid and rosuvastatin in patients at risk of cardiovascular events after noncardiac surgery: a pilot of the POISE-3 randomized controlled trial.

Marcucci Maura M Duceppe Emmanuelle E Le Manach Yannick Y Kearon Clive C Eikelboom John W JW Pohl Kayla K Vincent Jessica J Darvish-Kazem Saeed S Srinathan Sadeesh K SK Neary John D D JDD Parlow Joel L JL Kurz Andrea A Gross Peter L PL Mrkobrada Marko M Balasubramanian Kumar K Sessler Daniel I DI Devereaux P J PJ

Pilot and feasibility studies 20200721

<h4>Background</h4>Surgical bleeding is associated with postoperative cardiovascular complications. The efficacy and safety of tranexamic acid (TXA) in noncardiac surgery are still uncertain. Statins may prevent perioperative cardiovascular complications. We conducted a pilot to assess the feasibility of a perioperative trial of TXA and rosuvastatin.<h4>Methods</h4>Using a factorial design, we randomized patients at cardiovascular risk undergoing noncardiac surgery to intravenous TXA (1 g at the ...[more]

PMID: 32699643

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Project description:BackgroundFor 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.MethodsThe 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.DiscussionBleeding 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 registrationClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Project description:ImportanceMajor adverse cardiovascular and cerebrovascular events (MACCE) are a significant source of perioperative morbidity and mortality following noncardiac surgery.ObjectiveTo evaluate national trends in perioperative cardiovascular outcomes and mortality after major noncardiac surgery and to identify surgical subtypes associated with cardiovascular events using a large administrative database of United States hospital admissions.Design, setting, participantsPatients who underwent major noncardiac surgery from January 2004 to December 2013 were identified using the National Inpatient Sample.Main outcomes and measuresPerioperative MACCE (primary outcome), defined as in-hospital, all-cause death, acute myocardial infarction (AMI), or acute ischemic stroke, were evaluated over time.ResultsAmong 10 581 621 hospitalizations (mean [SD] patient age, 65.74 [12.32] years; 5 975 798 female patients 56.60%]) for major noncardiac surgery, perioperative MACCE occurred in 317 479 hospitalizations (3.0%), corresponding to an annual incidence of approximately 150 000 events after applying sample weights. Major adverse cardiovascular and cerebrovascular events occurred most frequently in patients undergoing vascular (7.7%), thoracic (6.5%), and transplant surgery (6.3%). Between 2004 and 2013, the frequency of MACCE declined from 3.1% to 2.6% (P for trend <.001; adjusted odds ratio [aOR], 0.95; 95% CI, 0.94-0.97) driven by a decline in frequency of perioperative death (aOR, 0.79; 95% CI, 0.77-0.81) and AMI (aOR, 0.87; 95% CI, 0.84-0.89) but an increase in perioperative ischemic stroke from 0.52% in 2004 to 0.77% in 2013 (P for trend <.001; aOR 1.79; CI 1.73-1.86).Conclusions and relevancePerioperative MACCE occurs in 1 of every 33 hospitalizations for noncardiac surgery. Despite reductions in the rate of death and AMI among patients undergoing major noncardiac surgery in the United States, perioperative ischemic stroke increased over time. Additional efforts are necessary to improve cardiovascular care in the perioperative period of patients undergoing noncardiac surgery.

Project description:ImportanceUnrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain.ObjectivesTo determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery.Design, setting, and participantsProspective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations.ExposuresObstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring.Main outcomes and measuresThe primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications.ResultsAmong a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio [HR], 1.49 [95% CI, 1.19-2.01]; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 [95% CI, 1.49-3.34]; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 [95% CI, 0.98-2.09]; P = .07) or mild OSA (adjusted HR, 1.36 [95% CI, 0.97-1.91]; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 [95% CI, 15.5-27.7] minutes) was longer than in those without (10.2 [95% CI, 7.8-10.9] minutes) (P < .001). No significant interaction effects on perioperative outcomes were observed with type of anesthesia, use of postoperative opioids, and supplemental oxygen therapy.Conclusions and relevanceAmong at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications. Further research would be needed to assess whether interventions can modify this risk.

Project description:ImportanceNearly 16 million surgical procedures are conducted in North America yearly, and postoperative cardiovascular events are frequent. Guidelines suggest functional capacity or B-type natriuretic peptides (BNP) to guide perioperative management. Data comparing the performance of these approaches are scarce.ObjectiveTo compare the addition of either N-terminal pro-BNP (NT-proBNP) or self-reported functional capacity to clinical scores to estimate the risk of major adverse cardiac events (MACE).Design, setting, and participantsThis cohort study included patients undergoing inpatient, elective, noncardiac surgery at 25 tertiary care hospitals in Europe between June 2017 and April 2020. Analysis was conducted in January 2023. Eligible patients were either aged 45 years or older with a Revised Cardiac Risk Index (RCRI) of 2 or higher or a National Surgical Quality Improvement Program, Risk Calculator for Myocardial Infarction and Cardiac (NSQIP MICA) above 1%, or they were aged 65 years or older and underwent intermediate or high-risk procedures.ExposuresPreoperative NT-proBNP and the following self-reported measures of functional capacity were the exposures: (1) questionnaire-estimated metabolic equivalents (METs), (2) ability to climb 1 floor, and (3) level of regular physical activity.Main outcome and measuresMACE was defined as a composite end point of in-hospital cardiovascular mortality, cardiac arrest, myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care.ResultsA total of 3731 eligible patients undergoing noncardiac surgery were analyzed; 3597 patients had complete data (1258 women [35.0%]; 1463 (40.7%) aged 75 years or older; 86 [2.4%] experienced a MACE). Discrimination of NT-proBNP or functional capacity measures added to clinical scores did not significantly differ (Area under the receiver operating curve: RCRI, age, and 4MET, 0.704; 95% CI, 0.646-0.763; RCRI, age, and 4MET plus floor climbing, 0.702; 95% CI, 0.645-0.760; RCRI, age, and 4MET plus physical activity, 0.724; 95% CI, 0.672-0.775; RCRI, age, and 4MET plus NT-proBNP, 0.736; 95% CI, 0.682-0.790). Benefit analysis favored NT-proBNP at a threshold of 5% or below, ie, if true positives were valued 20 times or more compared with false positives. The findings were similar for NSQIP MICA as baseline clinical scores.Conclusions and relevanceIn this cohort study of nearly 3600 patients with elevated cardiovascular risk undergoing noncardiac surgery, there was no conclusive evidence of a difference between a NT-proBNP-based and a self-reported functional capacity-based estimate of MACE risk.Trial registrationClinicalTrials.gov Identifier: NCT03016936.

Project description:Background and Purpose- Perioperative stroke is associated with significant morbidity and mortality. Conventional cardiovascular risk scores have not been compared to predict acute stroke after noncardiac surgery. Methods- Patients undergoing noncardiac surgery between 2009 and 2010 were identified from the US National Surgical Quality Improvement Program (n=540 717). Patients were prospectively followed for 30 days postoperatively for the primary outcome of stroke. Established cardiovascular and perioperative risk scores (CHADS2, CHA2DS2-VASc, Revised Cardiac Risk Index, Mashour et al risk score, Myocardial Infarction or Cardiac Arrest risk score, and National Quality Improvement Project American College of Surgeons surgical risk calculator) were assessed to predict perioperative stroke. Results- Stroke occurred in the perioperative period of 1474 noncardiac surgeries (0.27%). Patients with perioperative stroke were older, more frequently male, had lower body mass index, and were more likely to have undergone vascular surgery or neurosurgery than patients without stroke (P<0.001 for each comparison). All risk prediction models were associated with increased risk of perioperative stroke (C statistic [AUC] range, 0.743-0.836). The Myocardial Infarction or Cardiac Arrest risk score (AUC, 0.833) and American College of Surgeons surgical risk calculator (AUC, 0.836) had the most favorable test characteristics and a greater ability to discriminate perioperative stroke when compared with Revised Cardiac Risk Index, CHADS2, CHA2DS2-VASc, and Mashour risk scores (P for comparison, <0.001; Delong). Risk scores did not provide consistent discriminative ability across surgery types and were least predictive in vascular surgery (AUC range, 0.588-0.672). Conclusions- The Myocardial Infarction or Cardiac Arrest risk score and American College of Surgeons surgical risk calculator surgical risk scores provide excellent risk discrimination for perioperative stroke in most patients undergoing noncardiac surgery. Stroke prediction was less optimal in patients undergoing vascular surgery.

Project description:BackgroundThere is a potential role for tranexamic acid (TXA) use in foot and ankle procedures; however, the benefits of this intervention have not been fully elucidated. The purpose of this study was to explore the safety, outcomes, and medical complication profile of the use of intravenous TXA in patients undergoing foot and ankle surgery.MethodsA prospective study with retrospective review of 241 patients undergoing elective and traumatic foot and ankle procedures was performed. One gram of intravenous (IV) TXA was administered prior to incision. Patients were followed and evaluated for medical comorbidities, intraoperative blood loss, wound complication, superficial and deep infections, hematoma formation, medical complications, 30-day hospital readmission rate, and return visits to the emergency department or urgent care setting prior to first postoperative visit. Descriptive statistics were used for subgroup analysis. Mean postoperative follow-up was 4.5 months.ResultsEstimated blood loss in all cases was less than 20 mL. There was 1 case of superficial cellulitis (1/241, 0.4%), 1 deep infection after Achilles tendon repair (1/241, 0.4%), 4 cases of delayed wound healing (4/241, 1.6%), 1 instance of deep vein thrombosis (1/241, 0.4%), and 2 cases of postoperative pulmonary embolism (2/241, 0.8%). There were no instances of postoperative hematoma formation. There were no additional recorded thromboembolic events. There were no adverse drug reactions. There were no 30-day hospital readmissions or return visits to the emergency department or urgent care setting before the first postoperative visit. In a subgroup analysis, there was no significant difference in wound complications or infections between nondiabetics and diabetics (P > .05) and traumatic and nontraumatic cases (P > .05).ConclusionsThe use of IV TXA in foot and ankle surgeries was associated with low risk of wound complications, infections, hematoma formation, thromboembolic events, and overall complication rates with minimal side effect profile. Perioperative tranexamic acid use may prove to be beneficial in foot and ankle surgery patients but especially in higher-risk patients such as those with diabetes, trauma, and those that are immunocompromised.Level of evidenceLevel IV, case series.

Project description:BackgroundOlder adults undergoing noncardiac surgery have a high risk of major adverse cardiovascular events (MACE). This study aims to estimate the magnitude of increased perioperative risk, and examine national trends in perioperative MACE following in-hospital noncardiac surgery in older adults compared to middle-aged adults.DesignTime-series analysis of retrospective longitudinal data.SettingThe United States Agency for Healthcare Research and Quality National Inpatient Sample (NIS).ParticipantsHospitalizations for major noncardiac surgery among adults age ≥45 years between January 2004 and December 2014.MeasurementsInpatient perioperative MACE was defined as a composite of in-hospital death, myocardial infarction (MI), and ischemic stroke. In hospital death was determined from the NIS discharge disposition. MI and ischemic stroke were defined by International Classification of Diseases, Ninth Revision codes.ResultsOf an estimated 55,349,978 surgical hospitalizations, 26,423,039 (47.7%) were for adults age 45-64, 14,231,386 (25.7%) age 65-74, 10,621,029 (19.2%) age 75-84 years, and 4,074,523 (7.4%) age ≥85 years. MACE occurred in 1,601,022 surgical hospitalizations (2.9%). Adults 65-74 (2.8%; aOR 1.16, 95% CI 1.14-1.17), 75-84 years (4.5%; aOR 1.30, 95% CI 1.28-1.32), and ≥85 years (6.9%; aOR 1.55, 95% CI 1.52-1.57) had greater risk of MACE than those 45-64 years (1.7%). From 2004 to 2014, MACE declined among adults 65-74 (3.1-2.5%, p < 0.001), 75-85 years (4.9-3.9%, p < 0.001), and ≥85 years (7.7-6.1%, p < 0.001), but was unchanged for adults age 45-64. Declines in MACE were driven by decreased MI and mortality despite increased stroke.ConclusionOlder adults accounted for half of hospitalizations, but experienced the majority of MACE. Older adults had greater adjusted odds of MACE than younger individuals. The proportion of perioperative MACE declined over time, despite increases in ischemic stroke. These data highlight risks of noncardiac surgery in older adults that warrant increased attention to improve perioperative outcomes.

Dataset Information

Tranexamic acid and rosuvastatin in patients at risk of cardiovascular events after noncardiac surgery: a pilot of the POISE-3 randomized controlled trial.

Background

Methods

Results

Conclusions

Trial registration

Publications

Tranexamic acid and rosuvastatin in patients at risk of cardiovascular events after noncardiac surgery: a pilot of the POISE-3 randomized controlled trial.

Similar Datasets

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