Continuation versus discontinuation of antiplatelet therapy for bleeding and ischaemic events in adults undergoing non-cardiac surgery.
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ABSTRACT:
SUBMITTER: Lewis SR
PROVIDER: S-EPMC6513221 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
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Continuation versus discontinuation of antiplatelet therapy for bleeding and ischaemic events in adults undergoing non-cardiac surgery.
Lewis Sharon R SR Pritchard Michael W MW Schofield-Robinson Oliver J OJ Alderson Phil P Smith Andrew F AF
The Cochrane database of systematic reviews 20180718
<h4>Background</h4>Antiplatelet agents are recommended for people with myocardial infarction and acute coronary syndromes, transient ischaemic attack or stroke, and for those in whom coronary stents have been inserted. People who take antiplatelet agents are at increased risk of adverse events when undergoing non-cardiac surgery because of these indications. However, taking antiplatelet therapy also introduces risk to the person undergoing surgery because the likelihood of bleeding is increased. ...[more]
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Project description:IntroductionAntiplatelet therapy is commonly used in primary or secondary prevention of atherosclerotic and thrombotic diseases, such as coronary artery disease, transient ischaemic attack or stroke. Recent studies noted that antiplatelet therapy should be continued perioperatively in patients at high risk of thrombosis and low bleeding risk in orthopaedic, spinal or urological surgery. However, evidence in neurosurgery is lacking. Thus, we aim to conduct a systematic review and meta-analysis to assess whether the continuous use of antiplatelet drugs in neurosurgery increases the risk of perioperative bleeding.Methods and analysisWe will search PubMed, Cochrane Central Register of Controlled Trials and Embase using a strategy that combines the terms aspirin, bleeding/ischaemic and neurosurgery. Two reviewers will independently screen all identified abstracts for eligibility and evaluate the risk of bias of the included studies using the Cochrane risk of bias tool for randomised controlled studies and the Newcastle-Ottawa Scale for observational studies (including cohort studies, case-control studies, case series). Discrepancies will be resolved by consultation with a third researcher. We will conduct a systematic review and meta-analysis. If evidence suggests moderate statistical or clinical heterogeneity, we plan to investigate this heterogeneity by performing subgroup analyses and sensitivity analysis.Ethics and disseminationNo ethics approval will be sought as no original data will be collected for this review. Findings will be disseminated through peer-reviewed publication and conference presentations.Prospero registration numberCRD42020202590.
| S-EPMC8487199 | biostudies-literature
Project description:Background and aimsHaemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear.MethodsFrom 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin-angiotensin system inhibitors were withheld for different durations (2-3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy.ResultsTwo hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45-1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16-1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)].ConclusionsDiscontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.
| S-EPMC10984566 | biostudies-literature
Project description:IntroductionBleeding is the main safety concern of treatment with antiplatelet drugs. We aimed to refine prediction of major bleeding on antiplatelet treatment after a transient ischaemic attack (TIA) or stroke by assessing the added value of new predictors to the existing S2TOP-BLEED score.Patients and methodsWe used Cox regression analysis to study the association between candidate predictors and major bleeding among 2072 patients with a transient ischaemic attack or ischaemic stroke included in a population-based study (Oxford Vascular Study - OXVASC). An updated model was proposed and validated in 1094 patients with a myocardial infarction included in OXVASC. Models were compared with c-statistics, calibration plots, and net reclassification improvement.ResultsIndependent predictors for major bleeding on top of S2TOP-BLEED variables were peptic ulcer (hazard ratio (HR): 1.72; 1.04-2.86), cancer (HR: 2.40; 1.57-3.68), anaemia (HR: 1.55; 0.99-2.44) and renal failure (HR: 2.20; 1.57-4.28). Addition of those variables improved discrimination from 0.69 (0.64-0.73) to 0.73 (0.69-0.78) in the TIA/stroke cohort (p = 0.01). Performance improved particularly for upper gastro-intestinal bleeds (0.70; 0.64-0.75 to 0.77; 0.72-0.82). Net reclassification improved over the entire range of the score (net reclassification improvement: 0.56; 0.36-0.76). In the validation cohort, discriminatory performance improved from 0.68 (0.62-0.74) to 0.70 (0.64-0.76).Discussion and conclusionPeptic ulcer, cancer, anaemia and renal failure improve predictive performance of the S2TOP-BLEED score for major bleeding after stroke. Future external validation studies will be required to confirm the value of the STOP-BLEED+ score in transient ischaemic attack/stroke patients.
| S-EPMC7309362 | biostudies-literature
Project description:ContextThienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5 to 7 days prior to surgery to minimize bleeding.ObjectiveTo evaluate the use of cangrelor, an intravenous, reversible P2Y(12) platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery.Design, setting, and patientsProspective, randomized, double-blind, placebo-controlled, multicenter trial, involving 210 patients with an acute coronary syndrome (ACS) or treated with a coronary stent and receiving a thienopyridine awaiting CABG surgery to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n = 11) conducted between January 2009 and April 2011. Interventions Thienopyridines were stopped and patients were administered cangrelor or placebo for at least 48 hours, which was discontinued 1 to 6 hours before CABG surgery.Main outcome measuresThe primary efficacy end point was platelet reactivity (measured in P2Y(12) reaction units [PRUs]), assessed daily. The main safety end point was excessive CABG surgery-related bleeding.ResultsThe dose of cangrelor determined in 10 patients in the open-label stage was 0.75 μg/kg per minute. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary end point, PRU <240; 98.8% (83 of 84) vs 19.0% (16 of 84); relative risk [RR], 5.2 [95% CI, 3.3-8.1] P < .001). Excessive CABG surgery-related bleeding occurred in 11.8% (12 of 102) vs 10.4% (10 of 96) in the cangrelor and placebo groups, respectively (RR, 1.1 [95% CI, 0.5-2.5] P = .763). There were no significant differences in major bleeding prior to CABG surgery, although minor bleeding episodes were numerically higher with cangrelor.ConclusionsAmong patients who discontinue thienopyridine therapy prior to cardiac surgery, the use of cangrelor compared with placebo resulted in a higher rate of maintenance of platelet inhibition.Trial registrationclinicaltrials.gov Identifier: NCT00767507.
| S-EPMC3774162 | biostudies-literature
Project description:BackgroundInterruption of antithrombotic treatment before surgery may prevent bleeding, but at the price of increasing cardiovascular complications. This prospective study analysed the impact of antithrombotic therapy interruption on outcomes in non-selected surgical patients with known cardiovascular disease (CVD).MethodsAll 1200 consecutive patients (age 74.2 ± 10.2 years) undergoing major non-cardiac surgery (37.4 % acute, 61.4 % elective) during a period of 2.5 years while having at least one CVD were enrolled. Details on medication, bleeding, cardiovascular complications and cause of death were registered.ResultsIn-hospital mortality was 3.9 % (versus 0.9 % mortality among 17,740 patients without CVD). Cardiovascular complications occurred in 91 (7.6 %) patients (with 37.4 % case fatality). Perioperative bleeding occurred in 160 (13.3 %) patients and was fatal in 2 (1.2 % case fatality). Multivariate analysis revealed age, preoperative anaemia, history of chronic heart failure, acute surgery and general anaesthesia predictive of cardiovascular complications. For bleeding complications multivariate analysis found warfarin use in the last 3 days, history of hypertension and general anaesthesia as independent predictive factors. Aspirin interruption before surgery was not predictive for either cardiovascular or for bleeding complications.ConclusionsPerioperative cardiovascular complications in these high-risk elderly all-comer surgical patients with known cardiovascular disease are relatively rare, but once they occur, the case fatality is high. Perioperative bleeding complications are more frequent, but their case fatality is extremely low. Patterns of interruption of chronic aspirin therapy before major non-cardiac surgery are not predictive for perioperative complications (neither cardiovascular, nor bleeding). Simple baseline clinical factors are better predictors of outcomes than antithrombotic drug interruption patterns.
| S-EPMC4160449 | biostudies-literature
Project description:Dual antiplatelet therapy (DAPT) is recommended following percutaneous coronary intervention (PCI) with drug-eluting stent (DES). DAPT is a risk factor for gastrointestinal bleeding. We aimed to quantify (1) the rate of gastroscopy within 12 months after PCI, (2) the rate of adverse cardiac events and gastroscopy-related bleeding complications within 30 days of gastroscopy, and (3) the association between antiplatelet therapy and these events.Patients receiving gastroscopy within 12 months of PCI were identified and two nested case-control analyses were performed within the PCI cohort by linking Danish medical registries. Cases were patients with adverse cardiac events (cardiac death, myocardial infarction, or stent thrombosis) or hemostatic intervention. In both studies, controls were patients with gastroscopy including biopsy without adverse cardiac events and hemostatic intervention, respectively. Medical records were reviewed to obtain information on exposure to DAPT.We identified 22 654 PCI patients of whom 1497 patients (6.6 %) underwent gastroscopy. Twenty-two patients (1.5 %) suffered an adverse cardiac event, 93 patients (6.2 %) received hemostatic intervention during or within 30 days of the index gastroscopy. Interrupting DAPT was associated with a 3.46 times higher risk of adverse cardiac events (95 %CI 0.49 - 24.7). Discontinuation of one antiplatelet agent did not increase the risk (OR 0.65, 95 %CI 0.17 - 2.47). No hemostatic interventions were caused by endoscopic complications.Gastroscopy can be safely performed in PCI patients treated with DES and single antiplatelet therapy while interruption of DAPT may be associated with an increased risk of adverse cardiac events.
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Project description:Background and aimsDue to the multitude of risk factors outlined in the guidelines, personalised dual antiplatelet therapy (DAPT) guidance after percutaneous coronary intervention (PCI) is complex. A simplified method was created to facilitate the use of risk stratification. We aimed to compare the predictive and prognostic value of the 'Zuidoost Nederland Hart Registratie' (ZON-HR) classification for bleeding risk with the PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent DAPT (PRECISE-DAPT) score and to determine the effect of ticagrelor monotherapy versus DAPT in patients with or without high bleeding risk (HBR).MethodsA post hoc analysis of the GLOBAL LEADERS trial was performed to compare the predictive value of the ZON-HR classification with the PRECISE-DAPT score. Also, the outcomes stratified by either method were compared and the interaction of HBR on the treatment effect was determined.ResultsThe required parameters for the ZON-HR classification (3.7% HBR) and PRECISE-DAPT score (16.6% HBR) were available in 99.9% and 93% of the patients, respectively. The ZON-HR classification had a lower sensitivity (0.09 vs 0.26) and a higher specificity (0.97 vs 0.84), positive predictive value (0.13 vs 0.08) and accuracy (0.92 vs 0.82). Regression analysis showed that both methods predicted hazard for bleeding risk with HRs of 1.87 (95% CI: 1.59 to 2.18) and 2.67 (95% CI: 2.10 to 3.41) for the PRECISE-DAPT score and ZON-HR classification, respectively. The omission of aspirin reduced bleeding events only in acute coronary syndrome (ACS) patients without HBR (HR: 0.74, 95% CI: 0.61 to 0.90, p value for interaction of HBR: 0.04).ConclusionsStratification for bleeding risk according to the ZON-HR classification was feasible in almost all patients and showed to be more conservative than the PRECISE-DAPT score with a consistent prognostic accuracy. The benefit of aspirin omission was the largest in ACS patients without HBR.Trial registration numberNCT01813435.
| S-EPMC11781092 | biostudies-literature
Project description:Preoperative antiplatelet drug use is common in patients undergoing coronary artery bypass grafting (CABG). The impact of these drugs on bleeding and blood transfusion varies. We hypothesize that review of available evidence regarding drug-related bleeding risk, underlying mechanisms of platelet dysfunction, and variations in patient response to antiplatelet drugs will aid surgeons as they assess preoperative risk and attempt to limit perioperative bleeding. The purpose of this review is to (1) examine the role that antiplatelet drugs play in excessive postoperative blood transfusion, (2) identify possible mechanisms to explain patient response to antiplatelet drugs, and (3) formulate a strategy to limit excessive blood product usage in these patients. We reviewed available published evidence regarding bleeding risk in patients taking preoperative antiplatelet drugs. In addition, we summarized our previous research into mechanisms of antiplatelet drug-related platelet dysfunction. Aspirin users have a slight but significant increase in blood product usage after CABG (0.5 U of nonautologous blood per treated patient). Platelet adenosine diphosphate (ADP) receptor inhibitors are more potent antiplatelet drugs than aspirin but have a half-life similar to aspirin, around 5 to 10 days. The American Heart Association/American College of Cardiology and the Society of Thoracic Surgeons guidelines recommend discontinuation, if possible, of ADP inhibitors 5 to 7 days before operation because of excessive bleeding risk, whereas aspirin should be continued during the entire perioperative period in most patients. Individual variability in response to aspirin and other antiplatelet drugs is common with both hyper- and hyporesponsiveness seen in 5 to 25% of patients. Use of preoperative antiplatelet drugs is a risk factor for increased perioperative bleeding and blood transfusion. Point-of-care tests can identify patients at high risk for perioperative bleeding and blood transfusion, although these tests have limitations. Available evidence suggests that multiple blood conservation techniques benefit high-risk patients taking antiplatelet drugs before operation. Guidelines for patients who take aspirin and/or thienopyridines before cardiac procedures include some or all of the following: (1) preoperative identification of high-risk patients using point-of-care testing; (2) withdrawal of aspirin or other antiplatelet drugs for a few days and delay of operation in patients at high risk for bleeding if clinical circumstances permit; (3) selective perioperative use of evidence-based blood conservation interventions (e.g., short-course erythropoietin, off-pump procedures, and use of intraoperative blood conservation techniques), especially in high-risk patients; and (4) platelet transfusions if clinical bleeding occurs.
| S-EPMC3331630 | biostudies-other
Project description:Intensive antiplatelet therapy did not reduce recurrent stroke/transient ischaemic attack (TIA) events as compared with guideline treatment in the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial, but did increase the frequency and severity of bleeding. In this pre-specified analysis, we investigated predictors of bleeding and the association of bleeding with outcome. TARDIS was an international prospective randomised open-label blinded-endpoint trial in participants with ischaemic stroke or TIA within 48 h of onset. Participants were randomised to 30 days of intensive antiplatelet therapy (aspirin, clopidogrel, dipyridamole) or guideline-based therapy (either clopidogrel alone or combined aspirin and dipyridamole). Bleeding was defined using the International Society on Thrombosis and Haemostasis five-level ordered categorical scale: fatal, major, moderate, minor, none. Of 3,096 participants, bleeding severity was: fatal 0.4%, major 1.5%, moderate 1.2%, minor 11.4%, none 85.5%. Major/fatal bleeding was increased with intensive as compared with guideline therapy: 39 vs. 17 participants, adjusted hazard ratio 2.21, 95% CI 1.24-3.93, p = 0.007. Bleeding events diverged between treatment groups in the 8-35 day period but not in the 0-7 or 36-90 day epochs. In multivariate analysis more, and more severe, bleeding events were seen with increasing age, female sex, pre-morbid dependency, increased time to randomisation, prior major bleed, prior antiplatelet therapy and in those randomised to triple vs guideline antiplatelet therapy. More severe bleeding was associated with worse clinical outcomes across multiple physical, emotional and quality of life domains.Trial registration ISRCTN47823388 .
| S-EPMC10359249 | biostudies-literature
Project description:BackgroundAntithrombotic drugs increase the risk of bleeding, especially in patients who need urgent surgery without an adequate wash-out period. This review aims to evaluate perioperative bleeding complications in patients on dual antiplatelet therapy (DAPT) or direct-acting oral anticoagulants (DOACs) undergoing high-bleeding risk cardiovascular surgery and to present currently available potential solutions to mitigate antithrombotic therapy-related bleeding complications.MethodsAs a first step, we searched for relevant articles, over the last 10 years, in Medline (PubMed) and abstracted clinical information based on pre-defined criteria for bleeding complications. In the next step, an additional search evaluating potential solutions to mitigate bleeding complications was performed. The literature screening and selection process followed the principles derived from the PRISMA statement.ResultsFrom all reviewed studies, a total of 19 articles could be included evaluating the risk for bleeding in cardiac surgery related to DAPT or DOACs and 10 papers evaluating antithrombotic drug reversal or removal in the setting of cardiovascular surgery. Reported bleeding rates ranged between 18% and 41%. The variability of the reported data is remarkable. Idarucizumab is reported to provide optimal perioperative hemostasis in up to 93% of patients. It has been observed that andexanet alfa causes unresponsiveness to the anticoagulant effects of heparin. Antithrombotic removal by intraoperative hemoadsorption is found to be associated with a significant decrease in re-thoracotomy rate, overall procedure duration, administered transfusion volumes, chest-tube drainage, and length of hospitalization.DiscussionBleeding complications in patients treated with DAPT or DOACs in cardiac surgery are high. New costly reversal agents are available but have not been sufficiently tested in the cardio-surgical setting so far. Interestingly, bleeding-related complications seem to be effectively reduced by applying innovative intraoperative hemoadsorption techniques. Expected results from the ongoing trials should provide better insights concerning the efficacy and safety of several potential solutions. Currently, the variability of reports and the deficit of high-quality studies in this specific setting represent the major limitation for the unbiased conclusion of this review.
| S-EPMC9442533 | biostudies-literature