Dataset Information

Use and safety of aprotinin in routine clinical practice: A European postauthorisation safety study conducted in patients undergoing cardiac surgery.

ABSTRACT:

Background

Aprotinin has been used to reduce blood loss and blood product transfusions in patients at high risk of major blood loss during cardiac surgery. Approval by the European Medicines Agency (EMA) for its current indication is limited to patients at high risk of major blood loss undergoing isolated coronary artery bypass graft surgery (iCABG).

Objective

To report current real-world data on the use and certain endpoints related to the safety of aprotinin in adult patients.

Design

The Nordic aprotinin patient registry (NAPaR) received data from 83 European centres in a noninterventional, postauthorisation safety study (PASS) performed at the request of the EMA.

Setting

Cardiac surgical centres committed to enrolling patients in the NAPaR.

Patients

Patients receiving aprotinin agreeing to participate.

Intervention

The decision to administer aprotinin was made by the treating physicians.

Main outcome measures

Aprotinin safety endpoints were in-hospital death, thrombo-embolic events (TEEs), specifically stroke, renal impairment, re-exploration for bleeding/tamponade.

Results

From 2016 to 2020, 5309 patients (male 71.5%; >75 years 18.9%) were treated with aprotinin; 1363 (25.7%) underwent iCABG and 3946 (74.3%) another procedure, including a surgical treatment for aortic dissection ( n = 660, 16.7%); 54.5% of patients received the full-dose regimen. In-hospital mortality in iCABG patients was 1.3% (95% CI, 0.66 to 1.84%) vs. 8.3% (7.21 to 8.91%) in non-iCABG patients; incidence of TEEs and postoperative rise in creatinine level greater than 44 μmol l -1 2.3% (1.48 to 3.07%) and 2.7% (1.79 to 3.49%) vs. 7.2% (6.20 to 7.79%) and 15.5% (13.84 to 16.06%); patients undergoing re-exploration for bleeding 1.4% (0.71 to 1.93%) vs. 3.0% (2.39 to 3.44%). Twelve cases of hypersensitivity/anaphylactic reaction (0.2%) were reported as Adverse Drug Reactions.

Conclusion

The data in the NApaR indicated that in this patient population, at high risk of death or blood loss undergoing cardiac surgery, including complex cardiac surgeries other than iCABG, the incidence of adverse events is in line with data from current literature, where aprotinin was not used.

Trial registration

EU PAS register number: EUPAS11384.

SUBMITTER: De Hert S

PROVIDER: S-EPMC9451913 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Use and safety of aprotinin in routine clinical practice: A European postauthorisation safety study conducted in patients undergoing cardiac surgery.

De Hert Stefan S Ouattara Alexandre A Royston David D van der Linden Jan J Zacharowski Kai K

European journal of anaesthesiology 20220629 8

<h4>Background</h4>Aprotinin has been used to reduce blood loss and blood product transfusions in patients at high risk of major blood loss during cardiac surgery. Approval by the European Medicines Agency (EMA) for its current indication is limited to patients at high risk of major blood loss undergoing isolated coronary artery bypass graft surgery (iCABG).<h4>Objective</h4>To report current real-world data on the use and certain endpoints related to the safety of aprotinin in adult patients.<h ...[more]

PMID: 35766393

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Project description:BackgroundBecause of recent concerns about the safety of aprotinin, we updated our 2007 Cochrane review that compared the relative benefits and risks of aprotinin and the lysine analogues tranexamic acid and epsilon aminocaproic acid.MethodsWe searched electronic databases, including CENTRAL, MEDLINE, EMBASE, Google and Google Scholar for trials of antifibrinolytic drugs used in adults scheduled for cardiac surgery. Searches were updated to January 2008. By comparing aprotinin and the 2 lysine analogues to control, we derived indirect head-to-head comparisons of aprotinin to the other drugs. We derived direct estimates of risks and benefits by pooling estimates from head-to-head trials of aprotinin and tranexamic acid or epsilon aminocaproic acid.ResultsFor indirect estimates, we identified 49 trials involving 182 deaths among 7439 participants. The summary relative risk (RR) for death with aprotinin versus placebo was 0.93 (95% confidence interval [CI] 0.69-1.25). In the 19 trials that included tranexamic acid, there were 24 deaths among 1802 participants. The summary RR was 0.55 (95% CI 0.24-1.25). From the risk estimates derived for individual drugs, we calculated an indirect summary RR of death with use of aprotinin versus tranexamic acid of 1.69 (95% CI 0.70-4.10). To calculate direct estimates of death for aprotinin versus tranexamic acid, we identified 13 trials with 107 deaths among 3537 participants. The summary RR was 1.43 (95% CI 0.98-2.08). Among the 1840 participants, the calculated estimates of death for aprotinin compared directly to epsilon aminocaproic acid was 1.49 (95% CI 0.98-2.28). We found no evidence of an increased risk of myocardial infarction with use of aprotinin compared with the lysine analogues in either direct or indirect analyses. Compared with placebo or no treatment, all 3 drugs were effective in reducing the need for red blood cell transfusion. The RR of transfusion with use of aprotinin was 0.66 (95% CI 0.61-0.72). The RR of transfusion was 0.70 (95% CI 0.61-0.80) for tranexamic acid, and it was 0.75 (95% CI 0.58-0.96) for use of epsilon aminocaproic acid. Aprotinin was also effective in reducing the need for re-operation because of bleeding (RR 0.48, 95% CI 0.34-0.67).InterpretationThe risk of death tended to be consistently higher with use of aprotinin than with use of lysine analogues. Aprotinin had no clear advantages to offset these harms. Either tranexamic acid or epsilon aminocaproic acid should be recommended to prevent bleeding after cardiac surgery.

Project description:BackgroundThere is controversy regarding optimal use of benzodiazepines during cardiac surgery, and it is unknown whether and to what extent there is variation in practice. We sought to describe benzodiazepine use and sources of variation during cardiac surgeries across patients, clinicians, and institutions.MethodsWe conducted an analysis of adult cardiac surgeries across a multicentre consortium of USA academic and private hospitals from 2014 to 2019. The primary outcome was administration of a benzodiazepine from 2 h before anaesthesia start until anaesthesia end. Institutional-, clinician-, and patient-level variables were analysed via multilevel mixed-effects models.ResultsOf 65 508 patients cared for by 825 anaesthesiology attending clinicians (consultants) at 33 institutions, 58 004 patients (88.5%) received benzodiazepines with a median midazolam-equivalent dose of 4.0 mg (inter-quartile range [IQR], 2.0-6.0 mg). Variation in benzodiazepine dosage administration was 54.7% attributable to institution, 14.7% to primary attending anaesthesiology clinician, and 30.5% to patient factors. The adjusted median odds ratio for two similar patients receiving a benzodiazepine was 2.68 between two randomly selected clinicians and 4.19 between two randomly selected institutions. Factors strongly associated (adjusted odds ratio, <0.75, or >1.25) with significantly decreased likelihoods of benzodiazepine administration included older age (>80 vs ≤50 yr; adjusted odds ratio=0.04; 95% CI, 0.04-0.05), university affiliation (0.08, 0.02-0.35), recent year of surgery (0.42, 0.37-0.49), and low clinician case volume (0.44, 0.25-0.75). Factors strongly associated with significantly increased likelihoods of benzodiazepine administration included cardiopulmonary bypass (2.26, 1.99-2.55), and drug use history (1.29, 1.02-1.65).ConclusionsTwo-thirds of the variation in benzodiazepine administration during cardiac surgery are associated with institutions and attending anaesthesiology clinicians (consultants). These data, showing wide variations in administration, suggest that rigorous research is needed to guide evidence-based and patient-centred benzodiazepine administration.

Project description:IntroductionThe European Medicines Agency restored aprotinin (APR) use for preventing blood loss in patients undergoing isolated coronary artery bypass graft (iCABG) in 2016 but requested the collection of patient and surgery data in a registry (NAPaR). The aim of this analysis was to evaluate the impact of APR reintroduction in France on the main hospital costs (operating room, transfusion and intensive unit stay) compared to the current use of tranexamic acid (TXA), which was the only antifibrinolytic available before APR reinstatement.MethodsA multicenter before-after post-hoc analysis to compare APR and TXA was carried out in four French university hospitals. APR use followed the ARCOTHOVA (French Association of Cardiothoracic and Vascular Anesthetists) protocol, which had framed three main indications in 2018. Data from 236 APR patients were retrieved from the NAPaR (N = 874); 223 TXA patients were retrospectively retrieved from each center database and matched to APR patients upon indication classes. Budget impact was evaluated using both direct costs associated with antifibrinolytics and transfusion products (within the first 48 h) and other costs such as surgery duration and ICU stay.ResultsThe 459 collected patients were distributed as: 17% on-label; 83% off-label. Mean cost per patient until ICU discharge tended to be lower in the APR group versus the TXA group, which resulted in an estimated gross saving of €3136 per patient. These savings concerned operating room and transfusion costs but were mainly driven by reduced ICU stays. When extrapolated to the whole French NAPaR population, the total savings of the therapeutic switch was estimated at around €3 million.ConclusionThe budget impact projected that using APR according to ARCOTHOVA protocol resulted in decreased requirement for transfusion and complications related to surgery. Both were associated with substantial cost savings from the hospital's perspective compared with exclusive use of TXA.

Project description:BackgroundThe utility of pulmonary artery catheters (PACs) and their measurements depend on a variety of factors including data interpretation and personnel training. This US multi-center, retrospective electronic health record (EHR) database analysis was performed to identify associations between PAC use in adult cardiac surgeries and effects on subsequent clinical outcomes.MethodsThis cohort analysis utilized the Cerner Health Facts database to examine patients undergoing isolated coronary artery bypass graft (CABG), isolated valve surgery, aortic surgery, other complex non-valvular and multi-cardiac procedures, and/or heart transplant from January 1, 2011, to June 30, 2015. A total of 6844 adults in two cohorts, each with 3422 patients who underwent a qualifying cardiac procedure with or without the use of a PAC for monitoring purposes, were included. Patients were matched 1:1 using a propensity score based upon the date and type of surgery, hospital demographics, modified European System for Cardiac Operative Risk Evaluation (EuroSCORE II), and patient characteristics. Primary outcomes of 30-day in-hospital mortality, length of stay, cardiopulmonary morbidity, and infectious morbidity were analyzed after risk adjustment for acute physiology score.ResultsThere was no difference in the 30-day in-hospital mortality rate between treatment groups (OR, 1.17; 95% CI, 0.65-2.10; p = 0.516). PAC use was associated with a decreased length of stay (9.39 days without a PAC vs. 8.56 days with PAC; p < 0.001), a decreased cardiopulmonary morbidity (OR, 0.87; 95% CI, 0.79-0.96; p < 0.001), and an increased infectious morbidity (OR, 1.28; 95% CI, 1.10-1.49; p < 0.001).ConclusionsUse of a PAC during adult cardiac surgery is associated with decreased length of stay, reduced cardiopulmonary morbidity, and increased infectious morbidity but no increase in the 30-day in-hospital mortality. This suggests an overall potential benefit associated with PAC-based monitoring in this population.Trial registrationThe study was registered at clinicaltrials.gov (NCT02964026) on November 15, 2016.

Project description:BackgroundThe administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts.MethodsThis was a single-center, double-blind, randomized, placebo-controlled trial. Patients ≤ 48 months old were enrolled between July 2018 and April 2019 and were randomly assigned to groups that received either placebo or levosimendan infusions for 48 h post-surgery, along with all other standard methods of care. LCOS incidence was the primary outcome of this study.ResultsA total of 187 patients were enrolled, of whom 94 and 93 received levosimendan and placebo, respectively. LCOS incidence did not differ significantly between the levosimendan and placebo groups (10 [10.6%] versus 18 [19.4%] patients, respectively; 95% confidence interval [CI] 0.19-1.13; p = 0.090) nor did 90-day mortality (3 [3.2%] versus 4 [4.3%] patients, CI 0.14-3.69, p = 0.693), duration of mechanical ventilation (median, 47.5 h and 39.5 h, respectively; p = 0.532), ICU stay (median, 114.5 h and 118 h, respectively; p = 0.442), and hospital stay (median, 20 days and 20 days, respectively; p = 0.806). The incidence of hypotension and cardiac arrhythmia did not differ significantly between the groups. Levels of levosimendan fell rapidly without any plateau in plasma concentrations during infusion. A multiple logistic regression indicated that randomization to the levosimendan group was a predictor of LCOS.ConclusionsProphylactic levosimendan administration was safe in pediatric patients and had some benefit to postoperative hemodynamic parameters, but failed to provide significant benefit with respect to LCOS or 90-day mortality relative to placebo.Trial registrationName of the registry: Safety evaluation and therapeutic effect of levosimendan on the low cardiac output syndrome in patients after cardiopulmonary bypass.Trial registration numberChiCTR1800016594. Date of registration: 11 June 2018. URL of trial registry record: http://www.chictr.org.cn/index.aspx.

Project description:ObjectivesExpedient extubation after cardiac surgery has been associated with improved outcomes, leading to postoperative extubation frequently during overnight hours. However, recent evidence in a mixed medical-surgical intensive care unit population demonstrated worse outcomes with overnight extubation. This study investigated the impact of overnight extubation in a statewide, multicenter Society of Thoracic Surgeons database.MethodsRecords from 39,812 patients undergoing coronary artery bypass grafting or valve operations (2008-2016) and extubated within 24 hours were stratified according to extubation time between 06:00 and 18:00 (day) or between 18:00 and 6:00 (overnight). Outcomes including reintubation, mortality, and composite morbidity-mortality were evaluated using hierarchical regression models adjusted for Society of Thoracic Surgeons predictive risk scores. To further analyze extubation during the night, a subanalysis stratified patients into 3 groups: 06:00 to 18:00, 18:00 to 24:00, and 24:00 to 06:00.ResultsA total of 20,758 patients were extubated overnight (52.1%) and were slightly older (median age 66 vs 65 years, P < .001) with a longer duration of ventilation (4 vs 7 hours, P < .001). Day and overnight extubation were associated with equivalent operative mortality (1.7% vs 1.7%, P = .880), reintubation (3.7% vs 3.4%, P = .141), and composite morbidity-mortality (8.2% vs 8.0%, P = .314). After risk adjustment, overnight extubation was not associated with any difference in reintubation, mortality, or composite morbidity-mortality. On subanalysis, those extubated between 24:00 and 06:00 exhibited increased composite morbidity-mortality (odds ratio, 1.18; P = .001) but no difference in reintubation or mortality.ConclusionsExtubation overnight was not associated with increased mortality or reintubation. These results suggest that in the appropriate clinical setting, it is safe to routinely extubate cardiac surgery patients overnight.

Dataset Information

Use and safety of aprotinin in routine clinical practice: A European postauthorisation safety study conducted in patients undergoing cardiac surgery.

Background

Objective

Design

Setting

Patients

Intervention

Main outcome measures

Results

Conclusion

Trial registration

Publications

Use and safety of aprotinin in routine clinical practice: A European postauthorisation safety study conducted in patients undergoing cardiac surgery.

Similar Datasets

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