Citrate versus unfractionated heparin for anticoagulation in continuous renal replacement therapy

Background Unfractionated heparin is the most commonly used anticoagulant in continuous renal replacement therapy （CRRT）, but it can increase the risk of bleeding. Citrate is a promising substitute. Our study was to assess the efficacy and safety of citrate versus unfractionated heparin in CRRT. Methods We searched the MEDLINE, the EMBASE, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure Database until up to November 2011 for randomized controlled trials comparing citrate with unfractionated heparin in adult patients with acute kidney injury prescribed CRRT. The primary outcome was mortality and the secondary outcomes included circuit survival, control of uremia, risk of bleeding, transfusion rates, acid-base statuses, and disturbance of sodium and calcium homeostasis. Results Four trials met the inclusion criteria. Meta-analysis found no significant difference between two anticoagulants on mortality. Less bleeding and more hypocalcemic episodes were with citrate. Citrate was superior or comparable to unfractionated heparin in circuit life. Conclusions Citrate anticoagulation in CRRT seems to be superior in reducing bleeding risk and with a longer or similar circuit life, although there is more metabolic derangement. Mortality superiority has not been approved.

A randomized comparative study of using enoxaparin instead of unfractionated heparin in the intervention treatment of coronary heart disease

Background Low molecular weight heparin （LMWH） was more effective than unfractionated heparin （UFH） in treating acute coronary syndrome （ACS）. However, it remains uncertain whether LMWH can be used in patients undergoing percutaneous coronary intervention （PCI） instead of UFH. This study aimed to evaluate the efficacy and safety of using enoxaparin instead of UFH in the intervention treatment of patients with coronary heart disease （CHD） .Methods From October 2003 to Febuary 2005, 966 patients with CHD were enrolled into this study. Among 966 patients, 455 patients received the PCI, including 283 patients with Non-ST segment elevation ACS （NSTEACS）, 511 patients did not received PCI due to mild, moderate lesions or were suitable for coronary artery bypass graft （CABG）. The 966 patients were randomized to enoxaparin group （484 patients） and UFH group （482 patients）. Patients in the enoxaparin group were given enoxaparin at least twice subcutaneously （1 ms/kg, q12 h） before catheterization. Plasma anti-Xa activity was determined 1-8 hours after the last dose of enoxaparin was determined. The catheterization was performed within 8 hours after the last dose of enoxaparin. The sheath was removed immediately after the procedure. Patients in the UFH group were given UFH 25 mg intravenously before coronary angiography. Additional 65 mg was given intravenously if PCI was to be performed. The sheath was removed 4 hours after the procedure. Results A total of 227 patients in the enoxaparin group and 228 patients in the UFH group received PCI. In the enoxaparin group, one patient developed acute thrombosis during PCI and resulted in acute myocardial infarction （AMI）, no acute or subacute thrombosis was found during hospitalization. In the UFH group, no acute or subacute thrombosis occurred during PCI procedure and hospitalization. Therefore, the incidence of major adverse cardiovascular events （MACEs） during the hospitalization was 0.44% in the enoxaparin group and 0 in the UFH group. In the enoxaparin group, the sheath was removed immediately after the procedure and 8 patients had hematoma on the puncture site. In the UFH group, the sheath was removed 4 hours after the procedure and 20 cases had hematoma on the puncture site. The incidence of hematoma on the puncture site was significantly higher in the UFH group than that in the enoxaparin group （P〈0.05）. Anti-Xa activity was determined in 174 patients in LMWH group. The mean anti-Xa activity was （0.87±0.23） U/ml, and 94.8% of them had anti-Xa activity 〉0.5 U/ml and 6.9% of the patient 〉1.2 U/ml. There was no death and AMI occurred in enoxaparin group, but one patient had AMI caused by subacute thrombosis in UFH group during 30-day follow-up. MACE rate at 30-day follow-up was 0 in enoxaparin group and 0.43% in UFH group. Conclusions The results of the study suggest that it is safe and efficient to give enoxaparin at least twice before the PCI procedure, and the sheath can be removed immediately after PCI. For NSTEACS patient who has received enoxaparin more than twice during the hospitalization can undergo PCI directly and no UFH is necessary before or during PCI.

Low-Dose Unfractionated Heparin with Sequential Enoxaparin in Patients with Diabetes Mellitus and Complex Coronary Artery Disease during Elective Percutaneous Coronary Intervention

Background： Despite its limitations, unfractionated heparin （UFH） has been the standard anticoagulant used during percutaneous coronary intervention （PCl）. This study compared the safety of low-dose UFH with sequential enoxaparin with that of UFH in patients with diabetes mellitus （DM） and complex coronary artery disease receiving elective PCl. Methods： In this retrospective study, 514 consecutive patients with atherosclerotic cardiovascular diseases and type 2 DM were admitted to the hospital and received selective PCI, from January 2013 to December 2015. All patients with PCl received low-dose UFH with enoxaparin （intraductal 50 U/kg UFH and 0.75 mg/kg enoxaparin, n = 254; UFH-Enox group） or UFH only （intraductal 100 U/kg UFH, n = 260; UFH group）. The study endpoints were major adverse cardiac events （MACEs）, namely death, myocardial infarction （MI）, stroke, target-vessel immediate revascularization （TVR）, and thrombolysis in MI （TIMI） major bleeding, within 30 days and 1 year after PCI. Any catheter thrombosis during the procedure was recorded. Results： Only one patient had an intraductal thrombus in the UFH group. At the 30-day follow-up, no MACE occurred in any group; seven and five cases of recurrent angina and/or rehospitalization were reported in the UFH-Enox and UFH groups, respectively; there was no significant difference between the two groups （χ^2= 0.11, P = 0.77）. There was no TIMI major bleeding in the groups. With respect to the 1-year endpoint, two cases of recurrent MI and two of TVRs were reported in the UFH-Enox group, whereas in the UFH group, one case of recurrent MI and three of TVRs were reported; no significant difference existed between the two groups （χ^2 0, P= 0.99）. There were 30 and 25 recurrent angina and/or rehospitalizations in the UFH-Enox and UFH groups, respectively; there was no significant difl＇erence between the two groups （χ^2 = 0.37, P= 0.57）. Conclusion： In elective PCI, low-dose UFH with sequential enoxaparin has similar effects and safety to the UFH-only method.

Unfractionated Heparin with Sequential Enoxaparin in Patients with Complex Coronary Artery Lesions during Percutaneous Coronary Intervention

Background： Unfractionated heparin （UFH）, despite its limitations, has been used as the primary anticoagulant alternative during the percutaneous coronary intervention （PCI）. Some studies indicated that intravenous enoxaparin could be an effective and safe option. Our team used enoxaparin alone at one time according to the guidelines （Class IIA） and found a little catheter thrombosis during PCI. We recommend a new anticoagulation strategy using enoxaparin in combination with UFH. Enoxaparin has a more predictable anticoagulant response with no need of repeatedly monitoring anticoagulation during PCI. This retrospective study aimed to evaluate the efficacy and safety of using enoxaparin in combination with UFH in PCI patients with complex coronary artery disease. Methods： Between January 2015 and April 2017, 600 PCI patients who received intravenous UFH at an initial dose of 3000 U plus intravenous enoxaparin at a dose of 0.75 mg/kg （observation group） and 600 PCI patients who received UFH at a dose of 100 U/kg （control group） were consecutively included in this retrospective study. The endpoints were postoperative 48-h thrombolysis in myocardial infarction （TIMI） bleeding and transfusion and 30-day and l-year major adverse cardio-cerebrovascular events （MACCE）. Results： Baseline clinical, angiographic, and procedural characteristics were similar between groups, except there was less stent implantation per patient in the observation group （2.13 vs. 2.25 in the control group, P = 0.002）. TIMI bleeding （3.3% vs. 4.7%） showed no significant difference between the observation group and control group. During the 30-day follow-up, the rate of MACCE was 0.9% in the observation group and 1.5% in the control group. There was no significant difference in the rates of MACCE, death, myocardial infarction, target vessel revascularization, cerebrovascular event, and angina within 30 days and 1 year after PC1 between groups as well as in the subgroup analysis of transfemoral approach. Conclusions： UFH with sequential enoxaparin has similar anticoagulant effect and safety as UFH in PCI of complex coronary artery disease.

Effects of Bivalirudin and Unfractionated Heparin on Liver and Renal Function in Chinese Patients with Coronary Artery Disease Undergoing Coronary Angiography with/without Percutaneous Coronary Intervention

Background and Aims:Unfractionated heparin(UFH)and bivalirudin are widely used as anticoagulants in cardiovascular medicine,including for thrombosis prevention during coronary angiography(CAG)and percutaneous coronary intervention(PCI).Little is known of the effects of UFH and bivalirudin on liver and kidney function in patients subjected to these procedures.This study compared the effects of bivalirudin and UFH on liver/renal function in patients with coronary artery disease who underwent CAG,with or without PCI.Methods:The study comprised 134 consecutive patients(40–89 years-old),who underwent CAG(or CAG and PCI);among them,66 and 68 patients were subject to,respectively,bivalirudin or UFH.The following indicators of liver/renal function were measured before and after the procedures:plasma alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen,estimated glomerular filtration rate(eGFR),creatinine clearance,and serum creatinine.Patients were further stratified by severity of chronic kidney disease(CKD),based on original eGFR.Results:Relative to baseline,in the bivalirudin group,ALT and AST were higher after CAG(p=0.005,0.025),while blood urea nitrogen and serum creatinine were lower(p=0.049,<0.001).In the UFH group,ALT,AST,eGFR,and creatinine clearance were lower after CAG(p≤0.001,all).Patients given bivalirudin with moderate or severe CKD,but not those with mild CKD,gained significant improvement in kidney function.Conclusions:Relative to UFH,bivalirudin may better safeguard the renal function of patients with coronary artery disease who undergo CAG,especially patients with moderate-to-severe renal insufficiency.UFH may cause less liver damage than bivalirudin.

Fondaparinux:A cornerstone drug in acute coronary syndromes

In acute coronary syndrome(ACS),the use of anticoagulants in conjunction with antiplatelet agents in the acute phase has resulted in reduced ischemic events and is more effective than either class of drug used alone.Though parenteral anticoagulation is essential at the time of diagnosis,a balance must be made between ischemic benefit and the increased risk of bleeding when prescribing anticoagulants.Adverse events associated with anticoagulants,such as heparin-induced thrombocytopenia,bleeding problems,and the need for close monitoring of anticoagulant activity,have contributed to finding agents that reduce these limitations.Studies like the Organization to Assess Strategies in Ischemic Syndromes 5 and 6 and their meta-analysis have proven the efficacy of Fondaparinux over the entire ACS spectrum.The convenience of administration(once daily),lack of monitoring,reduction in mortality,and better safety profile make Fondaparinux a simple and effective anti-coagulant for the management of ACS.