Perioperative management of antiplatelet treatment in patients undergoing isolated coronary artery bypass grafting in Dutch cardiothoracic centres.
ABSTRACT: BACKGROUND:International guidelines do not provide uniform recommendations regarding the use of antiplatelet treatment in the perioperative period in patients undergoing coronary artery bypass grafting (CABG). METHODS:A questionnaire was sent to all 16 cardiothoracic centres in the Netherlands to determine which antiplatelet treatment is used in the perioperative setting. Furthermore, a single-centre prospective observational cohort study was performed which included all patients undergoing isolated CABG in July 2014. RESULTS:Eleven centres responded to the survey. Acetylsalicylic acid monotherapy was discontinued before surgery in 6 centres. In patients with an acute coronary syndrome receiving dual antiplatelet therapy (DAPT), most centres discontinued the P2Y12 inhibitor preoperatively. DAPT was restarted after surgery in 4 centres. However, 6 centres continued DAPT in patients who had undergone coronary stenting within one month of surgery. In patients with coronary stents, variation in the management of antiplatelet therapy increased in proportion to the interval between stenting and surgery. A total of 70 patients were included in the registry. Acetylsalicylic acid monotherapy was discontinued in 51% of patients and restarted in all patients. P2Y12 inhibitor treatment was discontinued before surgery in 70% of patients and re-initiated after CABG in 29%. CONCLUSIONS:Major differences were observed in the preoperative and postoperative management of antiplatelet treatment between different Dutch cardiothoracic centres and within a single centre. Part of this variation is probably due to lack of evidence and differences between the current guidelines; however, many of the strategies were not in accordance with any of these guidelines.
Project description:We assessed the effectiveness of dual antiplatelet therapy (DAPT) post elective or urgent (i.e., post acute coronary syndrome [ACS]) coronary artery bypass graft surgery (CABG).We systematically searched MEDLINE, EMBASE, and the Cochrane Registry from inception to August 2015. Randomized controlled trials (RCTs) in adults undergoing CABG comparing either dual vs. single antiplatelet therapy or higher- vs. lower-intensity DAPT were identified.Nine RCTs (n?=?4,887) with up to 1y follow-up were included. Five RCTs enrolled patients post-elective CABG (n?=?986). Two multi-centre RCTs enrolled ACS patients who subsequently underwent CABG (n?=?2,155). These 7 RCTs compared clopidogrel plus aspirin to aspirin alone. Two other multi-centre RCTs reported on ACS patients who subsequently underwent CABG comparing higher intensity DAPT with either ticagrelor (n?=?1,261) or prasugrel (n?=?485) plus aspirin to clopidogrel plus aspirin. Post-operative anti-platelet therapy was started when chest tube bleeding was no longer significant, typically within 24-48 h. There were no differences in all-cause mortality in clopidogrel plus aspirin vs. aspirin RCTs; conversely, all-cause mortality was significantly lower in ticagrelor and prasugrel vs. clopidogrel RCTs (risk ratio[RR] 0.49, 95% confidence interval[CI] 0.33-0.71, p?=?0.0002; 2 RCTs, n?=?1695; I(2) ?=?0%; interaction p?<?0.01 compared to clopidogrel plus aspirin vs aspirin RCTs). There were no differences in myocardial infarctions, strokes, or composite outcomes. Overall, major bleeding was not significantly increased (RR 1.31, 95% CI 0.81-2.10, p?=?0.27; 7 RCTs, n?=?4500). There was heterogeneity (I(2) ? =?42%) due almost entirely to higher bleeding reported for the prasugrel RCT which included mainly CABG-related major bleeding (RR 3.15, 95% CI 1.45-6.87, p?=?0.004; 1 RCT, n?=?437).Most RCT data for DAPT post CABG is derived from subgroups of ACS patients in DAPT RCTs requiring CABG who resume DAPT post-operatively. Limited RCT data with heterogeneous trial designs suggest that higher intensity (prasugrel or ticagrelor) but not lower intensity (clopidogrel) DAPT is associated with an approximate 50% lower mortality in ACS patients who underwent CABG based on post-randomization subsets from single RCTs. Large prospective RCTs evaluating the use of DAPT post-CABG are warranted to provide more definitive guidance for clinicians.
Project description:<h4>Introduction</h4>Saphenous vein graft (SVG) is the most common conduit used for coronary artery bypass grafting (CABG) surgery. Unfortunately, SVG are associated with poor long-term patency rates; a significant predictor of re-operation rates and survival. As such, medical therapy to prevent SVG narrowing or occlusion is of paramount importance. Aspirin (ASA) monotherapy is the standard of care after CABG, to improve long-term major adverse cardiovascular events (MACE) and graft patency. Benefits of dual antiplatelet therapy (DAPT) have not been well established in all CABG patients. We present a protocol for a network meta-analysis (NMA) comparing the effects of various antiplatelet therapy regimens on SVG patency, mortality, and bleeding among adult patients following CABG.<h4>Methods</h4>We will search CENTRAL, MEDLINE, EMBASE, CINAHL ACPJC, and grey literature sources (AHA, ACC, ESC, and CCC conference proceedings, ISRCTN Register, and WHO ICTRP) for randomized controlled trials (RCTs) which fit our criteria. RCTs that evaluate different antiplatelet regimens at least 3-months after CABG and have any of SVG patency, mortality, MACE, and major bleeding as outcomes will be selected. We will perform title and abstract screening, full-text screening, and data extraction independently and in duplicate. Two independent reviewers will also assess risk of bias (ROB) for each study, as well as evaluate quality of evidence using the GRADE framework. We will use R to perform the NMA and use low-dose ASA as reference within our network. We will report results as odds ratios with confidence intervals for direct comparisons, and credible intervals for indirect or mixed comparisons. We will use the surface under the cumulative ranking curve (SUCRA) to estimate the ranking of interventions.<h4>Discussion</h4>Given the limited direct comparison of various antiplatelet regimens, a network approach is ideal to clarify the optimum antiplatelet therapy after CABG. We hope that our NMA will be the largest quantitative synthesis evaluating antiplatelet regimens among patients requiring CABG. It should inform clinicians and guideline developers in selecting the most effective and safest antiplatelet regimen.Systematic Review registration: International Prospective Register for Systematic Reviews (PROSPERO)-CRD42019127695.
Project description:Background Postoperative atrial fibrillation (POAF) is a frequent complication of coronary artery bypass graft (CABG) surgery. This arrhythmia occurs more frequently among patients who receive perioperative inotropic therapy (PINOT). Administration of nitrates with antiplatelet agents reduces the conversion rate of cyclic guanosine monophosphate to guanosine monophosphate. This process is associated with increased concentrations of free radicals, catecholamines, and blood plasma volume. We hypothesized that patients undergoing CABG surgery who receive PINOT may be more susceptible to POAF when nitrates are administered with antiplatelet agents. Methods Clinical records were examined from a prospectively maintained cohort of 4,124 patients undergoing primary isolated CABG surgery to identify POAF-associated factors. Results POAF risk was increased among patients receiving PINOT, and the greatest effect was observed when nitrates were administered with antiplatelet therapy. Adjustment for comorbidities did not substantively change the study results. Conclusions Administration of nitrates with certain antiplatelet agents was associated with an increased POAF risk among patients undergoing CABG surgery. Additional studies are needed to determine whether preventive strategies such as administration of antioxidants will reduce this risk.
Project description:'Real world' bleeding in patients exposed to different regimens of dual antiplatelet therapy (DAPT) and triple therapy (TT, DAPT plus an anticoagulant) have a clinical and economic impact but have not been previously quantified. We will use linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) data to assemble populations eligible for three 'target trials' in patient groups: percutaneous coronary intervention (PCI); coronary artery bypass grafting (CABG); conservatively managed (medication only) acute coronary syndrome (ACS). Patients ≥18 years old will be eligible if, in CPRD records, they have: ≥1 year of data before the index event; no prescription for DAPT or anticoagulants in the preceding 3 months; a prescription for aspirin or DAPT within 2 months after discharge from the index event. The primary outcome will be any bleeding event (CPRD or HES) up to 12 months after the index event. We will estimate adjusted HR for time to first bleeding event comparing: aspirin and clopidogrel (reference) versus aspirin and prasugrel or aspirin and ticagrelor after PCI; and aspirin (reference) versus aspirin and clopidogrel after CABG and ACS. We will describe rates of bleeding in patients prescribed TT (DAPT plus an anticoagulant). Potential confounders will be identified systematically using literature review, semistructured interviews with clinicians and a short survey of clinicians. We will conduct sensitivity analyses addressing the robustness of results to the study's main limitation-that we will not be able to identify the intervention group for patients whose bleeding event occurs before a DAPT prescription in CPRD. This protocol was approved by the Independent Scientific Advisory Committee for the UK Medicines and Healthcare Products Regulatory Agency Database Research (protocol 16_126R) and the South West Cornwall and Plymouth Research Ethics Committee (17/SW/0092). The findings will be presented in peer-reviewed journals, lay summaries and briefing papers to commissioners/other stakeholders. 76607611; Pre-results.
Project description:The risk for gastrointestinal bleeding from dual antiplatelet therapy (DAPT) with new antiplatelets (prasugrel/ticagrelor) compared to clopidogrel is unclear. AIM:To determine the risk and type of major (gastrointestinal bleeding requiring hospitalization) and minor (anemia and iron deficiency) gastrointestinal events with different types of DAPT. METHODS:Retrospective observational cohort study of patients who started DAPT after percutaneous coronary intervention. Follow-up was censored after 12 months of DAPT, when a major gastrointestinal event occurred, or when DAPT was discontinued. RESULTS:Among 1,327 patients (54.03% were treated with clopidogrel-based DAPT, 38.13% with ticagrelor-based DAPT, and 7.84% with prasugrel-based DAPT), 29.5% had at least one gastrointestinal event. Patients taking clopidogrel-DAPT were older, with more comorbidities, and higher gastrointestinal risk compared to those taking other DAPT regimens. Adjusted hazard ratios (HRs) showed no between-group differences in the risk for major (clopidogrel vs. new antiplatelets: HR 0.996; 95% confidence interval 0.497-1.996) and minor (HR 0.920; 0.712-1.189) gastrointestinal events. Most patients received proton pump inhibitors while on DAPT (93.3%) and after withdrawal (83.2%). CONCLUSION:Prasugrel- or ticagrelor-based DAPT was not associated with increased gastrointestinal bleeding risk when compared to clopidogrel-DAPT. New antiplatelets do not necessarily need to be restricted to patients with low gastrointestinal risk.
Project description:Objective:International guidelines recommend the use of dual antiplatelet therapy (DAPT) after transcatheter aortic valve implantation (TAVI). The recommended duration of DAPT varies between guidelines. In this two-part study, we (1) performed a structured survey of 45 TAVI centres from around the world to determine if there is consensus among clinicians regarding antiplatelet therapy after TAVI; and then (2) performed a systematic review of all suitable studies (randomised controlled trials (RCTs) and registries) to determine if aspirin monotherapy can be used instead of DAPT. Methods:A structured electronic survey regarding antiplatelet use after TAVI was completed by 45 TAVI centres across Europe, Australasia and the USA. A systematic review of TAVI RCTs and registries was then performed comparing DAPT duration and incidence of stroke, bleeding and death. A variance weighted least squared metaregression was then performed to determine the relationship of antiplatelet therapy and adverse events. Results:82.2% of centres routinely used DAPT after TAVI. Median duration was 3 months. 13.3% based their practice on guidelines. 11 781 patients (26 studies) were eligible for the metaregression. There was no benefit of DAPT over aspirin monotherapy for stroke (P=0.49), death (P=0.72) or bleeding (P=0.91). Discussion:Aspirin monotherapy appears to be as safe and effective as DAPT after TAVI.
Project description:This is the case of a 40-year-old female diagnosed with NSTEMI. She underwent coronary angiography and suffered from type F left main coronary artery dissection. After hemodynamic stabilization, she was transferred to the nearest cardiothoracic surgery unit and underwent emergency coronary artery bypass graft (CABG) surgery. This report highlights important concepts in the management of a rare complication and emphasizes the surgical treatment decision-making, underlying an unusual but effective treatment approach.
Project description:Identifying patients undergoing cardiothoracic surgery at high risk of Staphylococcus aureus surgical site infection (SSI) is a prerequisite for implementing effective preventive interventions. The objective of this study was to develop a risk prediction model for S. aureus SSI or bacteremia after cardiothoracic surgery based on pre-operative variables.Data from the Merck Phase IIb/III S. aureus vaccine (V710-P003) clinical trial were analyzed. In this randomized placebo-controlled trial, the effect of preoperative vaccination against S. aureus was investigated in patients undergoing cardiothoracic surgery. The primary outcome was deep/superficial S. aureus SSI or S. aureus bacteremia through day 90 after surgery. Performance, calibration, and discrimination of the final model were assessed.Overall 164 out of 7,647 included patients (2.1%) developed S. aureus infection (149 SSI, 15 bacteremia, 28 both). Independent risk factors for developing the primary outcome were pre-operative colonization with S. aureus (OR 3.08, 95% confidence interval [CI] 2.23-4.22), diabetes mellitus (OR 1.87, 95% CI 1.34-2.60), BMI (OR 1.02 per kg/m2, 95% CI 0.99-1.05), and CABG (OR 2.67, 95% CI 1.91-3.78). Although vaccination had a significant (albeit modest) protective effect, it was omitted from the model because its addition did not significantly change the coefficients of the final model and V710-vaccine development has been discontinued due to insufficient efficacy. The final prediction model had moderate discriminative accuracy (AUC-value, 0.72).Pre-operative S. aureus colonization status, diabetes mellitus, BMI, and type of surgical procedure moderately predicted the risk of S. aureus SSI and/or bacteremia among patients undergoing cardiothoracic surgery.
Project description:Hypercoagulability, assessed by the thrombelastography (TEG) assay, has in several observational studies been associated with an increased risk of post-procedural thromboembolic complications. We hypothesize that intensified antiplatelet therapy with clopidogrel and aspirin, as compared to aspirin alone, will improve saphenous vein graft patency in preoperatively TEG-Hypercoagulable coronary artery bypass surgery (CABG) patients and reduce their risk for thromboembolic complications and death postoperatively.This is a prospective randomized clinical trial, with an open-label design with blinded evaluation of graft patency. TEG-Hypercoagulability is defined as a TEG maximum amplitude above 69 mm. Two hundred and fifty TEG-Hypercoagulable patients will be randomized to either an interventional group receiving clopidogrel 75 mg daily for three months (after initial oral bolus of 300 mg) together with aspirin 75 mg or a control group receiving aspirin 75 mg daily alone. Monitoring of antiplatelet efficacy and on-treatment platelet reactivity to clopidogrel and aspirin will be conducted with Multiplate aggregometry. Graft patency will be assessed with Multislice computed tomography (MSCT) at three months after surgery.The present trial is the first randomized clinical trial to evaluate whether TEG-Hypercoagulable CABG patients will benefit from intensified antiplatelet therapy after surgery. Monitoring of platelet inhibition from instituted antithrombotic therapy will elucidate platelet resistance patterns after CABG surgery. The results could be helpful in redefining how clinicians can evaluate patients preoperatively for their postoperative thromboembolic risk and tailor individualized postoperative antiplatelet therapy.Clinicaltrials.gov Identifier NCT01046942.
Project description:Background:End-stage renal disease yields susceptibility to both ischemia and bleeding. The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is not established in dialysis patients, who are usually excluded from randomized studies. Since recent studies implied the benefits of prolonged DAPT >12?months in chronic kidney disease, we investigated the effectiveness and safety of prolonged DAPT in dialysis patients with higher cardiovascular risks. Methods:In this nationwide population-based study, we analyzed dialysis patients who underwent DES implantation from 2008 to 2015. Continued DAPT was compared with discontinued DAPT using landmark analyses, including free-of-event participants at 12 (n?=?2246), 15 (n?=?1925) and 18?months (n?=?1692) after DES implantation. The primary outcome was major adverse cardiovascular events (MACEs): a composite of mortality, nonfatal myocardial infarction, coronary revascularization and stroke. Major bleeding was a safety outcome. Inverse probability of treatment weighting Cox regression was performed. Results:Mean follow-up periods were 278.3-292.4?days, depending on landmarks. Overall, incidences of major bleeding were far lower than those of MACE. Continued DAPT groups showed lower incidences of MACE and higher incidences of major bleeding, compared with discontinued DAPT groups. In Cox analyses, continued DAPT reduced the hazards of MACE at the 12- [hazard ratio (HR) = 0.74, 95% confidence interval (CI) 0.61-0.90; P?=?0.003], 15- (HR = 0.78, 95% CI 0.64-0.96; P?=?0.019) and 18-month landmarks (HR = 0.79, 95% CI 0.63-0.99; P?=?0.041), but without a significant increase in major bleeding at 12 (HR = 1.39, 95% CI 0.90-2.16; P?=?0.14), 15 (HR = 1.13, 95% CI 0.75-1.70; P?=?0.55) or 18?months (HR = 1.27, 95% CI 0.83-1.95; P?=?0.27). Conclusions:Prolonged DAPT reduced MACE without significantly increasing major bleeding in patients who were event-free at 12?months after DES implantation. In deciding on DAPT duration, prolonged DAPT should be considered in dialysis patients.