Comparison Of Intravenous Enoxaparin Versus Unfractionated Heparin During Elective Percutaneous Coronary Intervention

PrefaceCoronary heart disease(CHD) is the most common desease in elderly people,and it is the leading cause of death in people, the treatment plan is based on the results of coronary arteriongraphy. The ratio of patients undergoing percutaneous coronary intervention(PCI) treatment is enlarged. It's hard to predict the anticoagulant intensity after administrate unfractionated heparin(UFH).Low molecular weight heparin(LMWH) is widely used in recently years. It displaced UFH in many anticoagulant areas due to its internal merit. Many clinical researches showed LMWHs possibly can replace UFH as anticoagulant drug during elective PCI.Enoxaparin sodium had been shown to have greater clinical efficacy than UFH, so I select enoxaparin as the administration drug of experimental group. Majority of anticoagulant intensity could not achieve the standard after given 70-100U/kg UFH which Guideline defined in elective PCI, so the objective of this trial is try to explain the following question: what the anticoagulant intensity will be after raise the injected dosage of UFH in PCI which guideline defined? If it is needed to monitor activated clotting time (ACT) after administration UFH with dose adjustment based on body weight(125U/kg, based on our experiences) during PCI and does the numerical value of ACT can achieve the standard which is defined following? If it is effective and safe after administration enoxaparin with dose adjustment based on body weight during PCI? Does it within the limit be defined? Need we monitering anti-Xa activity during PCI? Does it better than UFH in concurrent control? How is the feasibility of enoxaparin instead of UFH as anticoagulant therapy drug in elective PCI? The trial observed the effectiveness and safety of intravenous enoxaparin application in PCI and therapeutic effect compare to unfractionated heparin, and this trial is a preliminary investigation which objective is to investigate new anticoagulation therapeutics during PCI.Materials and Methods1．Group of patients74 patients were selected from circulation ward of The Fist Affiliated Hospital of China Medical University from January to December in 2006, included 47 men and 27 women,they are all treated with PCI. The patients meet inclusion and exclusion criteria were randomly divided into two groups with random digits table. Experimental group included 21 men and 11 women, 10 of them had myocardial infarction history and 11 had angina history,the mean age is 59．7(?)9．1years;control group included 26 men and 16 women, 15 of them had myocardial infarction history and 27 had angina history,the mean age is 60．1(?)9．8 years.2．Major reagents and drugsThe reagents kit called Coatest Heparin-25553963, include S-2222, Factor Xa, Buffer, Antithrombin,Normal Plasms, products of Chromogenix Company, Italy; enoxaparin is manufactuated by Sanofi-Aventis Company, trade name is Clexane;UFH is manufactrated by Xuzhou Wangbang Pharmaceuticals Co.,Ltd.3．MedicationPatients in control group received unfractionated heparin (125U/kg intravenous bolus), ACT was determined, define within 300(?)350 seconds is positive; patients in experimental group received enoxaparin (1．0 mg/kg intravenous bolus: trade name Clexane), and anti-Xa activity were determined , define 0．5(?)1．8IU/ml is positive. The two groups were follow-up visited 30 days. 4．Samples DeterminationIn control group, samples were tested after administrated UFH in 5',60', 120'.240' with Hemochron methods(the actived reagents are diatomaceous silica).BeckMan Du640 spectrophotometer is used to test anti-Xa activety in experimental group. Measurement principle in experimental group:Heparin + AT (excess) (?) [Heparin (?) AT][Heparin (?) AT]+FXa (excess) (?) [Heparin (?) AT (?) FXa] + FXa(remaining)S-2222(?)Peptide+pNA5．Statistical treatmentSPSS 12．0 sofeware was used to analyze data, All measurement data were demonstrated by Mean(?)SD((?) (?)S),counting data were checked with chi-square test, statistical significance was defined as P<0．05．ResultsThe ACT of 5min, 60min, 120min, 240min in control group is 371(?)39sec, 332(?)34sec, 258(?)39sec, 175(?)24sec respectively, 40．5% of them within the limit, 24 patients(57．1%) are in the state of over-anticoagulation except them, the ACT is 401(?)27sec. only one patient's ACT under 300 second;The maximum anti-Xa activety of experimental group is 0．91(?)0．27IU/ml, the minimum anti-Xa activety is 0．73(?)0．22IU/ml, 90．6% of the anti-Xa activities between the limit.There is inguinal groove hematoma happened in a patient, the anti-coagulation activity is 0．97IU/ml and 0．75IU/ml. The effective anticoagulant intensity has statistical significance between two groups.DiscussionUnfractionated heparin is widely used in patients undergoing percutaneous coronary intervention, the way of administration is intravenous bolus with fixed dose or according to the body weight. The therapeutic peak anticoagulant effect is observed shortly after UFH administration, the individual difference of anticoagulant sensitivity and UFH degradation is very big, the t of elimination phase is related to the injected dose, such as the t after administration of UFH of 100U/kg, 200U/kg, 400U/kg is 1hour, l.6hours, 2．5hours respectively, continue medication may not achieve steady state blood concentration, the reason is due to its dose-dependent kinetics of elimination phase and can be uptaked by endothelial system. So the anticoagulant effect after UFH administration is hard to predict, accordingly, measure ACT is needed to adjust UFH dose during interventional procedures. The quantities of PCI has largely increased, doctor's technical level has a great elevation, so the operation time reduced. Most doctors don't monitoring ACT according to my survey. The lowest ACT of effective anticoagulation level during procedure is not clear yet, so there is latent danger in the patients undergoing PCI, that mean, some patients undergoing PCI maybe not safe due to lower ACT.Low molecular weight heparin(LMWH) is fragment of UFH under chemical degradation or enzymolysis, the molecular weight is between 4000-6000．LMWH has the pentosan fragment which can be recognized by Anti-Thrombin-(?)(AT-(?)) the same as UFH, then it can restrain Factor Xa; the ability of restrain Factor (?)a is poor due to the lack of high molecular weight fragmeng contrast to UFH. The ratio between anti-Xa activity and anti-(?)a activity is obviously higher than UFH, it's 1: 1 in UFH and 2(?)4: 1 in different LMWHs.On the basis of cascade theory, tissue factor pathway is in charge of the start of blood coagulation, small volume of thrombin is generated after start, then it can activate Factor (?) which is the junction point of intrinsic pathway and tissue factor pathway, Factor (?) can activate Factor (?), then activated X(Xa) activate massive thrombin. 1 unit of Xa can activate 50U thrombin, the generation of thrombin will greatly reduce due to inhibit Xa which is the top of the cascade amplification. LMWH has higher anti-Xa/(?)a ratio, so the efficiency of inhibit thrombin is higher. LMWH is not easier to be inactivated by platelet factor 4, seldom binding plasma protein, endotheliocyte, macrophagus and extracellular matrix, so its anticoagulation activity is easier to predict.The trial showed that enoxaparin can be used as anti-coagulation drug in elective PCI, it's therapeutic effect is certain and effective, then it's no need to monitor anti-coagulation activity, it can remove the femoral artery sheath after intervention immediately, so it lighten doctor's workload, decrease patient's prostration time; after increase the administration doseage of UFH which Guideline defined, the effective rate of control group during intervention is only 40%,higher than the rate reported before, most patients outside of the effective rate are in the state of over-anticoagulation, no increased bleeding tendency was observed in these patients, that mean UFH of 125U/kg can be used in elective PCI as anti-coagulation drug.Conclusion1．Its safe and effective to give intravenous enoxaparin 1mg/kg as anti-coagulation drug in elective PCI,and we don't need monitoring anti-Xa activity.2．UFH of 125U/kg used in elective PCI exists over-anticoagulation problem,but no increased bleeding tendency was observed in these patients, then if we elevate the present scope of anticoagulant intensity properly,the administration of UFH is safe and effective, and don't need to monitor activared coagulation time.