A Randomized Comparison Study Of Recombinant Staphylokinase Versus Recombinant Tissue-type Tissue Plasminogen Activator For Coronary Artery Patency And Safety In Acute Myocardial Infarction

Objective: In this randomized perspective parallelcomparison study, in order to assess the efficacy of r-SAK(recombinant staphylokinase) for thrombolysis therapy of acuteST-segment elevation myocardial infarction, theinfarction-related coronary artery patency rate and myocardialtissue perfusion of infarction area were assessed by coronaryangiography (CAG) 90 minuters after infusion of r-SAK or r-tPA(recombinant tissue plasminogen activator). Acute complicationsand adverse events after administration of the two medicineswere observed for evaluating the safety of r-SAK for AMIthrombolysis and providing evidence for its clinic use. To probethe efficacy and safety of clopidogrel added to standardanti-platelet and anti-coagulation therapy adjunctive tothrombolysis at the same time.Methods: From December, 2003 to December, 2004, 48patients who had diagnosed first time acute ST-elevationmyocardial infarction according to the ACC/AHA criteria wererandomized to r-SAK group and r-tPA group, both with 24patients. Inclusion criteria:(1) persistent angina for more than30 minutes and cannot relived by nitroglycerin ; (2) greater orequal to 1-mm ST-segment elevation in two or more limb leadsor greater or equal to 2-mm ST-segment elevation in two or morecontiguous precordial leads on a 12-lead ECG; (3) symptomonset within 6 hours or less than 12 hours but ST-segment isstill elevating; (4) younger than 70 years or 75 years old withgood constitution; (5) understood and written informed consent.Exclusion criteria: (1) history of intracranial or subarachnoidhemorrhage, or ischemic stroke within 6 months; (2)uncontrolled hypertension (i.e., systolic pressure greater or equalto 180 mmHg and/or diastolic pressure greater or equal to 110mmHg despite adequate treatment); (3) cannot exclude aortadissection or aneurysm; (4) active bleeding, major surgery,significant trauma or biopsy within 2 weeks, or contradiction tocompress-demanding artery puncture; (5) intracerebralneoplasm, A-V malformation or aneurysm; (6) cardiac shock; (7)hemorrhagic retinopathy, fundi hemorrhage due to diabetes orother disease; (8) with renal or hepatic dysfunction, hemorrhagedisease; (9) hemostasis and coagulation disorder; (10)re-infarction at the same area of previous old myocardialinfarction; (11) plan to or been pregnant; (12) after resuscitation.After assignment to r-SAK group, 10mg r-SAK diluted up to50ml with saline before administration, 2mg (10mL) bolus over2 minutes, followed by an infusion of the remaining 8mg (40ml)over 30 minutes. While in r-tPA group, first 8mg bolus over 6minutes, then 42mg over a 90min period. 300mg oral orchewable aspirin and clopidogrel before thrombolysis, followedby a daily oral dose of 150 mg aspirin and 75 mg clopidogrel. A75U/kg heparin bolus was given as r-SAK or r-tPA wasinfusing for anti-coagulation treatment, followed promptly by48-hour continuous heparin infusion, adjusted to keep theAPTT within 1.5 to 2.0 times control, then changed to LMWH(low molecule weight heparin) subcurtaneous injection twice aday. Other medications were to be used as routine. CAG wereperformed at 90 min to confirm infarction location and IRA,stenosis was analysed QCA (quantitative computer angiography)system, IRA flow was evaluated by TIMI grades, myocardialtissue reperfusion was assessed by TMP (TIMI myocardialperfusion) grades. Acute complications and adverse events wererecorded during 30 days after thrombolysis. All data analyzedwith SAS 6.12 statistic software, Statistical significance wasdetermined by by P value <0.05.Results: There was no significant difference about age, sex,risk factors, angina before infarction, infarction location, Killipgrade and the mean interval from onset to thrombolysis betweenr-SAK and r-tPA group. Except one patient of r-SAK groupdied at 60 min due to mechanical complication and cardiac shock,the other 23 patients in r-SAK group and 24 patients in r-tPAgroup were performed CAG, there was no difference in IRAdistribution between the two groups, the IRA repatency rate(83.33% vs 70.83%, p=0.308), TIMI 3 flow (75.00% vs 62.25%,p=0.355),myocardial tissue reperfusion(75.00% vs 66.67%,p=0.530) in r-SAK group are slightly higher than those in r-tPAgroup, but the differences did not reach statistical significance.The acute complications during 30-day period after thrombolysis,include allergic reaction (4.17% vs 0, p=0.317), seriousarrhythmias (50.00% vs 54.17%, p=0.775), heart failure (25% vs33.33%, p=0.530), cardiac shock (4.17% vs 4.17%, p=1.000),IRA re-occluded (4.17% vs 8.33%, p=0.555), postinfarctionangina (25% vs 20.83%, p=0.734) and death (4.17% vs 0,p=0.317), have no significant difference between the two groups.The bleeding complications of r-SAK group were slightly less(8.33% vs 25.00%, p=0.125), but this difference was notstatistically significant. No statistic difference in adverse eventswas found between the two groups.Conclusions: r-SAK proved to be at least as effective asalteplase in inducing early coronary artery patency for acute STsegment elevation myocardial infarction without contrindicationfor thrombolysis. The safety of r-SAK thrombolysis therapy isat about the same level of that of r-tPA, not associate withexcess mortality and complications of arrhythmia, postinfarctionangina and hemorrhage. Clopidogrel in addition to aspirin andheparin as conjunctive therapy for thrombolysis can achievemore coronary recanalization, reduce reinfarction and othercardiac events, without promoting hemorrhagic complication.Asa safe and effective thrombolytic medicine, r-SAK has thepotential for clinic application. r-SAK has antigenicity,repeateduse should be avoided two weeks after initial therapy, although...