Heparin-induced DRESS syndrome in a paediatric patient and successful anaesthetic management in cardiovascular bypass surgery: case report.

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin. CASE PRESENTATION: We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia. CONCLUSION: The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.

Use of bivalirudin after initial heparin management among adult patients on long-term venovenous extracorporeal support as a bridge to lung transplant: A case series.

A growing body of evidence supports the use of bivalirudin as an alternative to unfractionated heparin (UFH) for the prevention of thrombotic events in patients on venovenous (VV) extracorporeal membrane oxygenation (ECMO). However, data in patients bridged to lung transplantation are limited. In this case series, we describe the outcomes of six patients who were transitioned from UFH to bivalirudin during their course of VV ECMO support as a bridge to lung transplantation. All six patients were on VV ECMO support until transplant, with a median duration of 73 days. Bivalirudin demonstrated a shorter time to first therapeutic activated thromboplastin time (aPTT) level. Additionally, time in therapeutic range was longer while patients were receiving bivalirudin compared to UFH (median 92.9% vs. 74.6%). However, major bleeding and thrombotic events occurred while patients were receiving either anticoagulant. Based on our experience, bivalirudin appears to be a viable option for anticoagulation in VV ECMO patients bridged to lung transplantation. Larger studies evaluating the optimal anticoagulation strategy in patients bridged to transplant are needed.

Bivalirudin in acute coronary syndromes.

INTRODUCTION: Bivalirudin, a bivalent direct thrombin inhibitor, has been developed to reduce bleeding without any trade-off in thrombotic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). AREAS COVERED: Despite showing a superior safety profile compared with unfractionated heparin (UFH), bivalirudin is not considered the anticoagulant of choice in ACS patients undergoing PCI, mainly because of an increased rate of acute stent thrombosis (ST) shown by several randomized controlled trials (RCTs), in addition to limited availability in certain countries and increased costs. However, RCTs on bivalirudin have been characterized by several confounding factors hindering the interpretation of its safety and efficacy compared with UFH among the spectrum of ACS patients. Furthermore, a significant body of evidence has demonstrated that the risk of acute ST can be mitigated by a full-dose infusion regimen following PCI, without compromising the favorable safety profile compared to UFH. EXPERT OPINION: In light of the increased understanding of the prognostic relevance of bleeding events and the excellent safety profile of bivalirudin, recent trial evidence may allow for this anticoagulant agent to reemerge and have a more prominent role in the management of ACS patients undergoing PCI.

Bivalirudin vs heparin in cardiac-cerebral ischemic and bleeding events among Chinese STEMI patients during percutaneous coronary intervention: a retrospective cohort study.

Although bivalirudin has been recently made available for purchase in China, large-scale analyses on the safety profile of bivalirudin among Chinese patients is lacking. Thus, this study aimed to compare the safety profile of bivalirudin and heparin as anticoagulants in Chinese ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). A total of 1063 STEMI patients undergoing PCI and receiving bivalirudin (n=424, bivalirudin group) or heparin (n=639, heparin group) as anticoagulants were retrospectively enrolled. The net adverse clinical events (NACEs) within 30 days after PCI were recorded, including major adverse cardiac and cerebral events (MACCEs) and bleeding events (bleeding academic research consortium (BARC) grades 2-5 (BARC 2-5)). The incidences of NACEs (10.1 vs 15.6%) (P=0.010), BARC 2-5 bleeding events (5.2 vs 10.3%) (P=0.003), and BARC grades 3-5 (BARC 3-5) bleeding events (2.1 vs 5.5%) (P=0.007) were lower in the bivalirudin group compared to the heparin group, whereas general MACCEs incidence (8.9 vs 6.4%) (P=0.131) and each category of MACCEs (all P>0.05) did not differ between two groups. Furthermore, the multivariate logistic analyses showed that bivalirudin (vs heparin) was independently correlated with lower risk of NACEs (OR=0.508, P=0.002), BARC 2-5 bleeding events (OR=0.403, P=0.001), and BARC 3-5 bleeding events (OR=0.452, P=0.042); other independent risk factors for NACEs, MACCEs, or BARC bleeding events included history of diabetes mellitus, emergency operation, multiple lesional vessels, stent length >33.0 mm, and higher CRUSADE score (all P<0.05). Thus, bivalirudin presented a better safety profile than heparin among Chinese STEMI patients undergoing PCI.

Bivalirudin versus heparin in STEMI after BRIGHT-4 trial: an updated meta-analysis.

BACKGROUND: The use of bivalirudin-based anticoagulation over heparin-based anticoagulation for coronary percutaneous intervention has been debated for a long time. Multiple trials have shown promising benefits of bivalirudin over heparin therapy with the most recent addition being the BRIGHT-4 trial. We performed a meta-analysis to assess evidence from these trials, focusing on the coronary intervention of the STEMI population. METHODS: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023394701). Databases were searched for relevant articles published before January 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4. RESULTS: Out of 2375 studies evaluated, 13 randomized control trials with 24 360 acute ST-elevation myocardial infarction patients were included for analysis. The bivalirudin-based anticoagulation reduced the net clinical events (OR 0.75, CI 0.61-0.92), major adverse cardiac or cerebral events (OR 0.85, CI 0.74-0.98), any bleeding (OR 0.61, CI 0.45-0.83), major bleeding (OR 0.54, CI 0.39-0.75), all-cause mortality (OR 0.79, CI 0.67-0.92) and cardiac mortality (OR 0.78, CI 0.65-0.93) significantly without increasing the risk of any stent thrombosis (OR 0.92, 95% CI 0.52-1.61), definite stent thrombosis (OR 1.17, 95% CI 0.62-2.22) and acute stent thrombosis (OR 2.06, 95% CI 0.69-6.09) significantly at 30 days. CONCLUSION: Based on this meta-analysis, bivalirudin plus a post-PCI high-dose infusion-based anticoagulation during STEMI PCI has significant benefits over heparin therapy for cardiovascular outcomes without a significant increase in the risk of thrombotic outcomes.

Bivalirudin Versus Heparin During PCI in NSTEMI: Individual Patient Data Meta-Analysis of Large Randomized Trials.

BACKGROUND: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI. METHODS: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding. RESULTS: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P=0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P<0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up. CONCLUSIONS: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

One-year clinical outcomes of bivalirudin versus unfractionated heparin in patients with type 2 diabetes undergoing elective percutaneous coronary intervention.

BACKGROUND: Patients with diabetes and coronary artery disease have a higher risk of bleeding and thrombotic events. However, data on the safety and efficacy of bivalirudin in these patients undergoing elective percutaneous coronary intervention (PCI) are lacking. METHODS: 1152 patients undergoing elective PCI anticoagulated with bivalirudin and 10,250 patients anticoagulated with unfractionated heparin (UFH) (with or without glycoprotein IIb/IIIa inhibitors [GPI]) were performed propensity-score matching method. The thrombotic endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). The bleeding endpoint was according to the Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding. RESULTS: Finally, 376 (bivalirudin group) and 878 (UFH group) patients with type 2 diabetes (T2D) were enrolled. After one-year follow-up, there were 130 (10.4%) MACCE and 27 (2.2%) bleeding events occurred. Multivariate COX regression analysis showed no significant difference for MACCE between bivalirudin group and UFH group (P > 0.05). Further analysis showed that there was a reduction in the risk of myocardial infarction (MI) between two groups (Hazard ratio [HR] = 0.199, 95% confidence interval [CI]: 0.047-0.845, P = 0.029), but not in the risk of death, revascularization, stent thrombosis or stroke (all P > 0.05). As for BARC 2, 3 or 5 bleeding, no significant difference was found between two groups (P > 0.05). CONCLUSIONS: Although diabetes is considered a high-risk factor for poor prognosis, compared with UFH (with or without GPI), bivalirudin did not increase the risk of MACCE and even decreased the risk of MI in patients with T2D undergoing elective PCI, while the risk of bleeding was similar between two groups.

Periprocedural antithrombotic strategies in acute coronary syndromes undergoing percutaneous coronary intervention: Have we discarded bivalirudin too soon?

BACKGROUND: Publication of the BRIGHT-4 trial results has restimulated discussion about the optimal periprocedural antithrombotic strategy for patients undergoing percutaneous coronary intervention (PCI) with acute coronary syndromes (ACS). It is possible that variation in the infusion duration, may contribute to observed differences in safety-efficacy profiles of bivalirudin in this clinical setting. METHODS: Up to December 2022, randomized controlled trials (RCTs) comparing bivalirudin (either administered peri-procedurally or accompanied by postprocedural infusion) and heparin, both with or without GPI, were searched and entered in a frequentist network meta-analysis. Co-primary endpoints were trial-defined major adverse composite events (MACE) and major bleeding. Incident rate ratios (IRR) and 95 % confidence intervals (CI) were estimated. RESULTS: 10 RCTs (N = 57,137 patients/month) were included. As compared to heparin, prolonged bivalirudin infusion resulted in lower rates of major bleeding (IRR 0.58, 95 % CI 0.36-0.91), but there was no differences in MACE rates between these strategies. With regard to NACE, prolonged bivalirudin infusion yielded lower risk (IRR 0.86, 95 % CI 0.77-0.96), whereas both bivalirudin and heparin increased risk when coupled with GPI (IRR 1.24, 95 % CI 1.01-1.51 and IRR 1.24, 95 % CI 1.06-1.44, respectively). Both these combination strategies also increased minor bleeding rates (IRR 1.49, 95 % CI 1.16-1.93 and IRR 1.58, 95 % CI 1.29-1.95, respectively, for bivalirudin and heparin). Results were consistent across several sensitivity analyses. CONCLUSION: In patients with ACS undergoing PCI, procedural bivalirudin administration followed by prolonged infusion results in lower major bleeding rates, but there does not appear to be a difference in observed MACE.

Impact of Bivalirudin on Patients with Acute Coronary Syndrome Undergoing Rotational Atherectomy in Real-Life Setting: A Retrospective Cohort Study.

BACKGROUND: No evidence exists on the impact of bivalirudin in patients with the acute coronary syndrome undergoing rotational atherectomy. This study aimed to evaluate the impact of bivalirudin on patients with acute coronary syndrome undergoing rotational atherectomy. METHODS: This was a retrospective cohort study conducted in our hospital between January 2017 and December 2019. The study included patients with acute coronary syndrome undergoing rotational atherectomy. Furthermore, 2 cohorts were included in this study (bivalirudin cohort and control cohort unfractionated heparin). The primary end-point was in-hospital net adverse clinical events. The secondary endpoint was all-cause mortality at 23 months. RESULTS: The study included 157 patients with 33 (21.0%) in the bivalirudin cohort and 124 (79.0%) in the control cohort. Net adverse clinical events during hospitalization in the bivalirudin cohort were higher than that in the control cohort [9 (27.3%) vs. 14 (11.3%), P = .021]. However, there was no significant difference in all-cause mortality at 23 months between the 2 cohorts [25 (20.2%) vs. 10 (30.3%), P =.214]. After adjusting for potential confounders, the usage of bivalirudin was not associated with net adverse clinical event (odds ratio = 0.90; 95% CI: 0.18-4.45; P =.890), and the hazard ratio for all-cause mortality at 23 months was 1.01 (95% CI: 0.33-3.15; P =.983). CONCLUSION: Bivalirudin appears to exhibit a similar impact as unfractionated heparin on patients with acute coronary syndrome undergoing rotational atherectomy in real-life setting.

Impact of coronary artery disease on clinical outcomes after TAVR: Insights from the BRAVO-3 randomized trial.

OBJECTIVE: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact. METHODS: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure. RESULTS: Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding). CONCLUSION: CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD.

Bivalirudin versus heparin anticoagulation in patients receiving extracorporeal membrane oxygenation.

OBJECTIVE: Bivalirudin has been suggested as an alternative to heparin for anticoagulation in patients receiving extracorporeal membrane oxygenation (ECMO). Nevertheless, there is limited evidence about the benefit of bivalirudin in ECMO patients compared with heparin. Hence, we conducted a meta-analysis to assess the effect of bivalirudin versus heparin on clinical outcomes in patients receiving ECMO. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched from inception up to 1 April 2022 for cohort studies and randomized controlled trials comparing bivalirudin versus heparin in patients who received ECMO. The primary outcome was short-term death. Secondary outcomes included thrombotic events and bleeding events. RESULTS: We selected 12 retrospective cohort studies with 1232 ECMO patients focusing on bivalirudin anticoagulation (n = 497) versus heparin anticoagulation (n = 735). Two hundred and one of 497 patients (40.4%) in the bivalirudin group versus 350 of 735 patients (47.6%) in the heparin group did not survive to hospital discharge. Compared with the heparin group, bivalirudin anticoagulation did not significantly decrease in-hospital mortality in patients receiving ECMO (RR, 0.95; 95% CI, 0.79-1.13; p = 0.546). Fifty-seven of 374 patients (15.2%) in the bivalirudin versus 99 of 381 patients (26.0%) in the heparin group suffered from thrombotic events. Compared with the heparin group, bivalirudin anticoagulation did not significantly decrease the rate of thrombotic events for patients receiving ECMO (RR, 0.78; 95% CI, 0.45-1.35; p = 0.378). However, bivalirudin anticoagulation significantly decreased the incidence of bleeding events compared to the heparin group (RR, 0.48; 95% CI, 0.25-0.95; p = 0.035). CONCLUSIONS: Compared with heparin anticoagulation, bivalirudin did not decrease the rates of short-term mortality and thrombotic events, but reduced the incidence of bleeding events in patients receiving ECMO.

Use of bivalirudin for anticoagulation in pediatric extracorporeal membrane oxygenation (ECMO).

This study describes the use of bivalirudin in children on extracorporeal membrane oxygenation (ECMO). Pediatric patients receiving bivalirudin were compared to patients receiving heparin as the anticoagulant on ECMO. Data was collected for children under 18 years of age supported by ECMO from January 2016 to December 2019. Data collected included demographics, diagnosis, ECMO indication, type, and duration, indication for bivalirudin use, dose range, activated partial thromboplastin time (aPTT) levels, minor and major bleeding, hemolysis, and mortality. Forty pediatric patients received ECMO; eight received bivalirudin primarily for anticoagulation. The median age was 4 months (IQR 0.5, 92) in the heparin cohort, 0.6 months (IQR 0.0, 80.0) in the primary bivalirudin cohort. The indication for ECMO was respiratory in 5 patients (18%) in the heparin group versus 6 (75%) in the primary bivalirudin group, cardiac in 18 (67%) in heparin versus 1 (12.5%) in primary bivalirudin, and extracorporeal-cardiopulmonary resuscitation (E-CPR) in 4 (15%) in heparin versus 1 (12.5%) in primary bivalirudin. Bivalirudin was the initial anticoagulant for eight patients (66.6%) while three (25%) were switched due to concern for heparin-induced thrombocytopenia (HIT) and one (8%) for heparin resistance. The median time to achieve therapeutic aPTT was 14.5 hours compared to 12 hours in the heparin group. Sixty-five percent of aPTT values in the bivalirudin and 44% of values in the heparin group were in the therapeutic range in the first 7 days. Patients with primary bivalirudin use had significantly lower dose requirement at 12 (p = 0.003), 36 (p = 0.007), and 48 (p = 0.0002) hours compared to patients with secondary use of bivalirudin. One patient (12.5%) had major bleeding, and two patients (25%) required circuit change in the primary bivalirudin cohort. Bivalirudin may provide stable and successful anticoagulation in children. Further large, multicenter studies are needed to confirm these findings.

Outcomes of systemic bivalirudin and sodium bicarbonate purge solution for Impella 5.5.

BACKGROUND: Impella 5.5 (Abiomed; Danvers, MA) (IMP5) is a commonly used, surgically implanted, tMCS device that requires systemic anticoagulation and purge solution to avoid pump failure. To avoid heparin-induced thrombocytopenia (HIT) from unfractionated heparin (UFH) use, our program has explored the utility of bivalirudin (BIV) for systemic anticoagulation and sodium bicarbonate-dextrose purge solution (SBPS) in IMP5.5. METHODS: This single center, retrospective study included 34 patients supported on IMP5.5 with BIV based AC and SBPS between December 1st 2020 to December 1st 2021.The efficacy and safety end points were incidence of development of HIT, Tissue Plasminogen Activator (tPA) use for suspected pump thrombosis, stroke, and device failure as well as clinically significant bleeding. RESULTS: The median duration of IMP5.5 support was 9.8 days (IQR: 6-15). Most patients were bridged to HTX (58%) followed by recovery (27%) and LVAD implantation (15%). Patients were therapeutic on bivalirudin for 64% of their IMP5.5 support. One patient (2.9%) suffered from ischemic stroke and 26.5% (9) patients developed clinically significant bleeding. tPA was administered to 7(21%) patients. One patient in the entire cohort developed HIT. CONCLUSIONS: Our experience supports the use of systemic BIV and SBPS as a method to avoid heparin exposure in a patient population predisposed to the development of HIT.

Comparison of Bivalirudin Versus Heparin for Anticoagulation During Extracorporeal Membrane Oxygenation.

The effect and safety of bivalirudin compared with heparin in patients undergoing extracorporeal membrane oxygenation (ECMO) remains unclear. Therefore, we conducted a systematic review and meta-analysis to compare the effectiveness and safety of heparin and bivalirudin in patients who underwent ECMO. We searched Embase, the Cochrane Central Register of Controlled Trials, and MEDLINE. Inclusion criteria included patients (1) undergoing ECMO and (2) receiving bivalirudin or heparin. We excluded studies where the majority of patients switched heparin to bivalirudin or vice versa during the clinical course. The primary outcome was short-term mortality. We presented the results of all analyses with the use of random-effects models. Eleven studies reported short-term mortality. The use of bivalirudin was associated with significantly lower short-term mortality, compared with heparin (odds ratio: 0.71, 95% confidence interval, 0.55-0.92; p = 0.01, I2 = 7%). In this meta-analysis of observational studies, the use of bivalirudin was associated with significantly lower short-term mortality, compared with heparin. Further prospective studies are warranted to clarify this finding.

Heparin Versus Bivalirudin for Anticoagulation in Adult Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

Extracorporeal membrane oxygenation (ECMO) poses unique thrombotic and hemorrhagic risks, and the optimal anticoagulant choice is unknown. We systematically searched Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection for randomized-, crossover-, retrospective cohort-, or parallel-designed clinical studies of adult patients receiving ECMO that compared heparin recipients with bivalirudin recipients. Meta-analysis was performed with random-effects models. The ROBINS-I tool was used to assess the risk of bias. Six retrospective observational studies met the inclusion criteria for the qualitative summary. Five studies were suitable for meta-analysis. Those who received heparin were more likely to experience circuit-related thrombosis (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.25-3.37, p = 0.005, I2 = 0%) and die (OR 1.62, 95% CI 1.19-2.21, p = 0.002, I2 = 0%) compared with those who received bivalirudin. There were no differences in major bleeding events between heparin and bivalirudin recipients (OR 1.83, 95% CI 0.55-6.09, p = 0.33, I2 = 82.7%). In retrospective settings compared with heparin anticoagulation, bivalirudin was associated with less circuit-related thrombotic events and greater survival in adults supported on ECMO, without contributing to more bleeding complications. Prospective controlled studies comparing heparin and bivalirudin in adult ECMO patients are warranted to corroborate these findings.

Safety and Efficacy of Bivalirudin versus Unfractionated Heparin Monotherapy in Patients with CAD and DM Undergoing PCI: A Retrospective Observational Study.

Introduction: Optimal anticoagulants for patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) are unclear. This retrospective observational study is aimed at evaluating efficacy and safety of bivalirudin versus unfractionated heparin (UFH) monotherapy in patients with DM undergoing PCI. Methods: A total of 3890 diabetic patients receiving PCI in the General Hospital of Northern Theater Command were divided into the bivalirudin group (n = 869) and the UFH group (n = 3021) according to different anticoagulant therapy regimens. Indication for PCI was in accordance with current guidelines including national cardiovascular data registry. The primary endpoint was 30-day net adverse clinical events (NACEs). The secondary endpoints included 30-day major adverse cardiac and cerebral events (MACCEs), bleeding events defined according to the Bleeding Academic Research Consortium (BARC) definition, and stent thrombosis (ST). Patients were matched by propensity score at a ratio of 1 : 1. Results: After propensity score matching, the bivalirudin group was associated with a lower incidence of NACEs (3.0% vs. 6.0%, P = 0.003) than the UFH group. The incidence of MACCE (1.7% vs. 3.3%, P = 0.033) was significantly lower in the bivalirudin group, mainly due to a lower mortality rate (0.6% vs. 2.0%, P = 0.010). In addition, patients in the bivalirudin group had less bleeding (1.4% vs. 3.0%, P = 0.022) than those in the UFH group, although BARC 2, 3, and 5 bleeding (0.1% vs. 0.6%, P = 0.218) was numerically lower. Conclusion: In diabetic patients undergoing PCI, bivalirudin was significantly associated with reduced risks of 30-day NACE and MACCE, mainly driven by the lower rates of bleeding and mortality, compared with heparin monotherapy.

Safety of Bivalirudin Combined with Ticagrelor in the Emergency PCI in Patients with Acute ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: The present study aimed to investigate the application safety of bivalirudin combined with ticagrelor in the emergency percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: From October 1, 2018, to December 30, 2019, 210 patients with STEMI admitted to the Department of Cardiology who underwent emergency PCI were randomly divided into the bivalirudin group (group A, N = 105) and the unfractionated heparin group (group B, N = 105). Before the emergency PCI operation after admission, the loading dose of aspirin (300 mg) was given orally, and then 100 mg/d. At the same time, the loading dose of ticagrelor (180 mg) was administered orally, and then 90 mg/bid. The adverse events and the hemorrhage events 30 days after the operation were observed and recorded. RESULTS: There were five hemorrhage cases in the bivalirudin group, with one case of secondary hemorrhage and four cases of mild hemorrhage. There were 14 hemorrhages in the unfractionated heparin group with one case of secondary hemorrhage and thirteen cases of mild hemorrhage. In terms of mild hemorrhage, the hemorrhage rate in the bivalirudin group was significantly lower than that in the unfractionated heparin group (3.8% vs. 12.4%, P = 0.040). One patient died in the unfractionated heparin group, while no deaths occurred in the bivalirudin group during the thirty days of follow-up. No myocardial infarction, revascularization, or stroke occurred in the two groups within 30 days after the operation. CONCLUSION: Compared with unfractionated heparin combined with ticagrelor in patients with STEMI undergoing emergency PCI treatment, bivalirudin combined with ticagrelor could significantly reduce the occurrence of mild hemorrhage events, and it would not increase the incidence of MACE during the 30 days of follow-up.