Humans ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors

The efficacy of low molecular weight heparin (LMWH) with low dose unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) with or without glycoprotein (Gp) IIb/IIIa inhibitor compared to UFH with or without Gp IIb/IIIa inhibitor has not been elucidated. Between October 2005 and July 2007, 2,535 patients with ST elevation acute myocardial infarction (STEMI) undergoing PCI in the Korean Acute Myocardial Infarction Registry (KAMIR) were assigned to either of two groups: a group with Gp IIb/IIIa inhibitor (n=476) or a group without Gp IIb/IIIa inhibitor (n=2,059). These groups were further subdivided according to the use of LMWH with low dose UFH (n=219) or UFH alone (n=257). The primary end points were cardiac death or myocardial infarction during the 30 days after the registration. The primary end point occurred in 4.1% (9/219) of patients managed with LMWH during PCI and Gp IIb/IIIa inhibitor and 10.8% (28/257) of patients managed with UFH and Gp IIb/IIIa inhibitor (odds ratio [OR], 0.290; 95% confidence interval [CI], 0.132-0.634; P=0.006). Thrombolysis In Myocardial Infarction (TIMI) with major bleeding was observed in LMHW and UFH with Gp IIb/IIIa inhibitor (1/219 [0.5%] vs 1/257 [0.4%], P=1.00). For patients with STEMI managed with a primary PCI and Gp IIb/IIIa inhibitor, LMWH is more beneficial than UFH.
Acute Disease ; Aged ; Drug Therapy, Combination ; Female ; Hemorrhage ; Heparin/*therapeutic use ; Heparin, Low-Molecular-Weight/*therapeutic use ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Infarction/epidemiology/mortality/*therapy ; Myocardial Revascularization ; Odds Ratio ; Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors/metabolism ; Prognosis ; Registries

BACKGROUNDAntithrombotic and antiplatelet therapies have been proposed to treat non-ST elevation acute coronary syndrome (NSTEACS), yet limited information is available about their applications from a multicenter "real-world" clinical procedure, especially in China. This study was undertaken to characterize the use of antithrombotic and antiplatelet agents in relation to the risk levels of the NSTEACS patients who were enrolled in Sino-Global Registry of Acute Coronary Events (GRACEs) registry study.

METHODSWe analyzed the data from 618 Chinese NSTEACS patients stratified into low-(n = 151), intermediate-(n = 233), and high-risk groups (n = 234) based on GRACE risk scores. The baseline characteristics, clinical presentations, antithrombotic and antiplatelet agents were recorded and compared among the three groups.

RESULTSThe administration rates of low-molecular-weight heparins (LMWHs) (86.08%) and thienopyridines (85.92%) were higher whereas the administration rate of glycoprotein IIb/IIIa inhibitor (1.78%) was much lower than those reported previously. Meanwhile, within the first 24 hours of admission, the use of heparin/LMWHs in the high-risk group was more than that in the intermediate- and low-risk groups (73.50% vs 63.09% vs 55.63%, P = 0.001). Furthermore, the combination of antithrombotic and antiplatelet medications showed no significant differences in all groups.

CONCLUSIONSIn the "real world" practice of China, the antithrombotic and antiplatelet therapies on NSTEACS are well adherent to the current guidelines except for several gaps, such as the very low use of glycoprotein IIb/IIIa inhibitor. Moreover, these antithrombotic and antiplatelet treatments usually tend to be underused for the high-risk ones.

Acute Coronary Syndrome ; drug therapy ; Aged ; Coronary Disease ; drug therapy ; Female ; Fibrinolytic Agents ; therapeutic use ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; Pyridines ; therapeutic use ; Registries ; Risk Assessment

Batifiban, a synthetic cyclic peptide, is a potent platelet glycoprotein GPIIb/IIIa antagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects, and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55, 110, or 220 microg/kg, or multiple doses of an bolus followed intravenous infusion for 24 h (180 microg/kg plus 2.0 microg/min.kg, and 220 microg/kg plus 2.5 microg/min.kg) in this phase I clinical trial. Plasma levels of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma levels of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner, consistent with its mechanism as a GPIIb/IIIa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.
Injections, Intravenous ; Peptides, Cyclic/*pharmacokinetics ; Peptides, Cyclic/*pharmacology ; Platelet Aggregation Inhibitors/adverse effects ; Platelet Aggregation Inhibitors/*pharmacokinetics ; Platelet Aggregation Inhibitors/*pharmacology ; Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors ; Young Adult

PURPOSE: This study was designed as a multicenter, randomized, open-label study to evaluate the efficacy and tolerability of Clotinab(TM). We expected to obtain same results as with ReoPro(R) in improving ischemic cardiac complications in high-risk patients who were about to undergo percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Patients of 19-80 years of age with acute coronary syndrome (ACS) who were about to undergo PCI were enrolled. After screening and confirmation of eligibility, patients were randomly assigned to different groups. Clotinab(TM) was given to 84 patients (58.7+/-10.6 years, M:F=68:16)and ReoPro(R)(59.0+/-10.5 years, M:F=30:10) was given to 40 patients before PCI. The primary efficacy endpoint was the onset of major adverse cardiac event (MACE) within 30 days from day 1. The tolerability endpoints were assessed based on bleeding, thrombocytopenia, change in Hb/Hct, human antichimetric antibody development, and adverse events. RESULTS: The number of Clotinab(TM) patients experiencing MACE was 0 out of 76 per protocol (PP) patients. The MACE rate was 0%, and its 95% exact CI was [0.00-4.74%]. A major bleeding event developed in 3 patients in the ReoPro(R) group. The probability of MACE onset in Clotinab(TM) was estimated to be less than 5%. There was no clinically significant result in tolerability variables. CONCLUSION: Clotinab(TM) is an effective and safe medicine in preventing ischemic cardiac complications for high-risk patients who will receive PCI.
Acute Coronary Syndrome/surgery ; Adult ; Aged ; Aged, 80 and over ; *Angioplasty, Transluminal, Percutaneous Coronary ; Antibodies, Monoclonal/adverse effects/*therapeutic use ; Drugs, Investigational/adverse effects/therapeutic use ; Female ; Humans ; Immunoglobulin Fab Fragments/adverse effects/*therapeutic use ; Male ; Middle Aged ; Myocardial Ischemia/prevention & control ; Platelet Aggregation Inhibitors/adverse effects/*therapeutic use ; Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors ; Prospective Studies ; Risk Factors ; Treatment Outcome

BACKGROUNDAspirin and clopidogrel can improve myocardial reperfusion and alleviate myocardial injury during percutaneous coronary intervention (PCI). Whether the addition of intravenous tirofiban during this procedure produces further benefit has not been clarified in ST segment elevation myocardial infarction (STEMI) patients. We evaluated this on STEMI patients who underwent primary PCI (p-PCI) via transradial artery approach.

METHODSConsecutive patients were randomized into tirofiban group (n=72) or placebo group (n=78). Angiographic analysis included initial and final thrombolysis in myocardial infarction (TIMI) flow grade (TFG), corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) of the thrombotic vessel. Platelet aggregation rate (PAR), creatine phosphokinase (CPK), CPK isoenzyme MB (CPK-MB) and troponin I levels were measured and TIMI definitions were used to assess bleeding complications. Left ventricular performance parameters were investigated with equilibrium radionuclide ventriculography. Major adverse cardiac events (MACE) were followed up for 6 months.

RESULTSThe cases of TFG 0 and 1 before PCI, TFG 0 when first crossing of guide wire were less, and the cases of TFG 3 after PCI was more in tirofiban group than those in placebo group. The final CTFC was fewer and the incidence of no reflow phenomenon was lower, as well the percentage of final TFG 3 was higher in tirofiban group than those in placebo group (all P<0.05). Mean peak CPK-MB was significantly lower, while the left ventricular performance parameters 1 week after PCI were much more improved in tirofiban group than those in the placebo group. PAR was significantly decreased shortly after tirofiban infusion. The incidence of 6-month MACE in tirofiban group was obviously lower than that in the placebo group. No statistical difference was noted between the two groups with regard to bleeding complications.

CONCLUSIONSIntravenous tirofiban infusion, in addition to aspirin and clopidogrel in STEMI patients with p-PCI via transradial artery access, can quickly inhibit platelet aggregation, loosen occlusive thrombus, improve myocardial reperfusion and reduce incidence of MACE with few complications of vessel access and bleeding.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; methods ; Aspirin ; administration & dosage ; adverse effects ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; physiopathology ; therapy ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; Ticlopidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Tyrosine ; administration & dosage ; adverse effects ; analogs & derivatives ; Vasodilation

BACKGROUNDPrimary percutaneous coronary intervention (PCI) has been identified as the first therapeutic option for patients with acute ST-segment elevation myocardial infarction (STEMI). The strategy of transferring patient to a PCI center was recently recommended for those with acute STEMI who were present to PCI incapable hospitals, which include lack of facilities or experienced operators. In China, some local hospitals have been equipped with PCI facilities, but they have no interventional physicians qualified for performing primary PCI. This study was conducted to assess the feasibility, safety and efficacy of the strategy of transferring physician to a PCI-equipped hospital to perform primary PCI for patients with acute STEMI.

METHODSThree hundred and thirty-four consecutive STEMI patients with symptom presentation = 12 hours in five local hospitals from November 2005 to November 2007 were randomized to receive primary PCI by either physician transfer (physician transfer group, n=165) or patient transfer (patient transfer group, n=169) strategy. Door-to-balloon time, in-hospital and 30-day major adverse cardiac events (MACE, including death, non-fatal re-infarction, and target vessel revascularization) were compared between the two groups.

RESULTSBaseline characteristics between the two groups were comparable. Thrombolysis in myocardial infarction (TIMI) 3 flow was revealed in more patients in the physician transfer group at initial angiography (17.6% vs 10.1%, P<0.05). The success rate of primary PCI (96.3% vs 95.4%, P>0.05) and length of hospital stay were similar between the two groups ((15+/-4) days vs (14+/-3) days, P>0.05). In the physician transfer group, door-to-balloon time was significantly shortened ((95+/-20) minutes vs (147+/-29) minutes, P<0.0001) and more patients received primary PCI with door-to-balloon time less than 90 minutes (21.2% vs 7.7%, P<0.001). During hospitalization, MACE occurred in 6.7% and 11.2% of patients in the physician and patient transfer groups, respectively (P=0.14). At 30-day clinical follow-up, the occurrence rates of death, non-fatal re-infarction, and target vessel revascularization (TVR) were 3.6% vs 5.9%, 4.2% vs 8.9%, and 1.2% vs 2.4% in the physician and patient transfer groups, respectively (all P>0.05). The cumulative composite of MACE was significantly reduced (8.9% vs 17.2%, P=0.03) and MACE free survival (91.0% vs 82.9%, P<0.05) was significantly improved in the physician transfer group at 30 days.

CONCLUSIONThe strategy of transferring physician to local hospital to perform primary PCI for patients with acute STEMI is feasible, safe and efficient in reducing the door-to-balloon time and 30-day MACE rate.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; Female ; Hospital Communication Systems ; organization & administration ; Humans ; Interdisciplinary Communication ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Patient Care Team ; Patient Transfer ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; Time Factors

Integrin alphaIIbbeta3 of the platelet surfaces regulates the thrombosis formation. alphaIIbbeta3 binds to the RGD sequence (Arg-Gly-Asp) of fibrinogen, promotes the platelet aggregation and finally leads to the thrombus. We obtained the three-dimensional molecular structure of alphaIIbbeta3 using homology-modeling (modeller8v2 software), with integrin alphavbeta3 (pdb code 1JV2) as the template. Accordingly, a cyclic RGD(RGD-c) peptide was designed to bind alphaIIbbeta3 as an antagonist and to block the formation of thrombus. We added two amino acids X, Y to both sides of RGD-c. X and Y could bind to each other by disulfide bond that finally made RGD-c a cyclic peptide. The optimum structure of RGD-c was obtained from the energetic optimization processes. All amino acids were placed at the X and Y to conduct Molecular Docking to the integrin alphaIIbbeta3 We got the optimum structure of RGD-c by energetic optimization and the antagonistic combination analysis. The results might provide an insight into designing and screening integrin alphaIIbbeta3 antagonists.
Amino Acid Sequence ; Drug Design ; Humans ; Models, Molecular ; Oligopeptides ; chemistry ; Platelet Aggregation Inhibitors ; chemical synthesis ; chemistry ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; chemistry

OBJECTIVETo observe the safety and efficiency of ultra-early glycoprotein IIb/IIIa receptor blockade tirofiban use in patients with acute ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI).

METHODSFrom April 2005 to April 2006, 158 consecutive AMI patients (117 males, mean age of 58.8 +/- 25.2 years) were randomly received tirofiban (10 microg/kg bolus i.v. followed by 0.15 microgxkg(-1)xmin(-1) for 36 hours) before PCI in emergency room (early, n = 78) or immediately before PCI in catheterization lab (late, n = 80). Clinical and angiographic features between 2 groups before and after PCI were analyzed.

RESULTSBaseline clinical characteristics before PCI were similar between the two groups. Tirofiban was administered 39.8 minutes earlier in early group than that in the late group. The TIMI 3 flow rate (23.1% vs. 10.0%, P = 0.032) and the combined TIMI 2 or 3 flow rate (39.7% vs. 23.8%, P = 0.040) at initial angiography before PCI were significantly higher in early group than that in late group. However, TIMI 3 flow rate, myocardial Blush grade or corrected TIMI frames immediately after PCI were similar between the groups. The combined incidence of death or recurrent MI as well as bleeding complications or thrombocytopenia rate during early follow-up were similar between the groups (P > 0.05).

CONCLUSIONSEarly initiation of tirofiban in patients with acute STEMI treated by primary PCI was safe. A better patency (TIMI 3 and TIMI 2-3 flow) in infarct related artery was obtained in patients with early tirofiban administration.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; methods ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; physiopathology ; therapy ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; Tyrosine ; administration & dosage ; analogs & derivatives

OBJECTIVETo evaluate the early clinical result of percutaneous transluminal coronary intervention (PCI) and stenting on saphenous vein grafts.

METHODSPercutaneous intervention was performed in 91 saphenous vein grafts in 64 patients. The data of clinical results during operation and hospitalization and that of other interventional assisting device were recorded in database and were analyzed.

RESULTSThe success rate of operation was 95.3%, non-Q wave myocardial infarction occurred in 1 patient (1.6%) and temporary no-reflow phenomenon occurred in 4 patients (6.3%) during operation. Reduced antegrade flow and ventricular fibrillation happened in 1 patient after stenting and normal antegrade flow obtained after cardiac compression and tracheal intubation and insertion of IABP. The distal protection devices were used in 7 patients (10.9%), X-sizer extraction system in 4 patients. Platelet glycoprotein IIb/IIIa receptor blockers were administered in 25 patients (35.9%). Non-Q wave myocardial infarction occurred in two cases, the incidence of major adverse clinical event was 3.1% during the period of hospitalization.

CONCLUSIONSThe instant success rate of PTCA and stenting of saphenous vein bypass grafts is high and recent clinical result is promising, but the middle and long term results remain to be further followed. The use of distal embolic protection device and GPIIb/IIIa receptor blockers may improve its prognosis.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Artery Bypass ; Graft Occlusion, Vascular ; surgery ; Humans ; Male ; Middle Aged ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; Saphenous Vein ; surgery ; Treatment Outcome