Thrombolytics in Acute Myocardial Infarction

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<ul><li><p>Thrombolytics in Acute Myocardial Infarction Higher reperfusion rates are being achieved with updated agents </p><p>Intracoronary treatment: Streptokinase is usually infused at a rate of 2000-4000 U/min into the infarct-related artery. Infusion is continued for 30-60 min after reperfusion to eliminate any residual thrombi, and is followed by IV heparin therapy for 4-10 days. Antithrombotic therapy is then indicated with either warfarin or aspirin and dipyridamole. </p><p>Intravenous treatment: Current research employs high dose (500,000-1,500,000 U), brief duration (20-60 min) IV infusions of streptokinase. However, it is doubtful whether this regimen reduces the risk of systemic fibrinogenolysis. Fibrinolysis should always be documented by the appropriate haematology, and urokinase should be given to patients with recent streptococcal infection or streptokinase therapy within the previous 6-12 months. Whether heparin should be administered immediately after IV streptokinase, or delayed until the activated partial thromboplastin time has declined is the subject of controversy. </p><p>Complications: The incidence of serious bleeding after intracoronary streptokinase is 0-8%, and is no greater after IV streptokinase. Most bleeding requiring transfusion occurs at the arterial puncture site. Reperfusion arrhythmias (usually accelerated idioventricular rhythm) are mainly well tolerated and conventionally managed. Ventricular tachycardia and fibrillation are rare. In inferior MI, atrioventricular block may resolve with reperfusion. Complications of cardiac catheterisation are rare in experienced laboratories, as are febrile or allergic reactions to streptokinase. </p><p>Recanalisation and intracoronary therapy: Recanalisation rates with streptokinase are about 75% (50-90%), with a mean interval from treatment onset to reperfusion of 30 min. Factors affecting recanalisation are proximal vs distal thrombus location (74 vs 38%, respectively), left anterior descending vs right or left circumflex thrombosis (74 vs 44%, respectively), and no collaterals vs collaterals (66 vs 45%). Reperfusion is more likely if treatment is initiated within 6 hours of symptom onset. Resistant thrombosis may be caused by plaque haemorrhage, coronary artery dissection or coronary embolus. </p><p>Intravenous treatment: From 7 studies assessing reperfusion by coronary angiography, reperfusion was achieved in a total of 129/304 (42%) patients a mean of 45 min after treatment onset. Treatment initiated &lt; 4 hours from symptom onset achieved reperfusion in 59/175 (34%) patients and&gt; 4 hours in 70/129 (54%). Reperfusion rates are not closely associated with the total streptokinase dose. </p><p>Assessment of reperfusion after IV thrombolysis: Angiography does not determine very early 3 hours after symptom onset) or very late (several hours to 4 weeks) reperfusion, as not all patients can be catheterised at these times; hence, reperfusion rates with IV streptokinase are probably underestimated. Spontaneous reperfusion can also masquerade as drug-induced reperfusion. One study estimated spontaneous reperfusion rates of 77%, without thrombolytic therapy, 10-14 days post-MI. The most widely used non-invasive clinical marker of reperfusion is the time to peak creatine kinase activity, which is usually 20-25 hours after symptom onset without reperfusion, and 12-16 hours with reperfusion. Thalluim scintigraphy is another useful assessment but neither this nor creatine kinase peak activity can distinguish between spontaneous and drug-induced reperfusion. </p><p>Reocclusion occurs in 10-35% of patients and is associated with the severity of residual stenosis (0.4 mm2) and inadequate or interrupted anticoagulation. In some cases percutaneous transluminal coronary angioplasty (PTCA), or revascularisation is then warranted. However, the efficacy of acute thrombolysis + PTCA is unproven and will probably be limited in application. </p><p>Reperfusion and infarct size: Salvaged myocardium has been assessed by Q-wave regression and increased R-wave heights. Increased C-palmitate uptake in myocardial cells has also been demonstrated. Radionuclide ventriculography and two-dimensional echocardiography have demonstrated improved global and regional left ventricular function after reperfusion. Regional wall motion is probably the most sensitive method, as regional left ventricular function can be achieved without improvements in left ventricular ejection fractions, and also because there is little functional improvement when reperfusion occurs 3-4 hours after symptom-onset. </p><p>Reperfusion and mortality- Uncontrolled trials of intracoronary streptokinase have attributed lower mortalities to reperfused patients. However, they are more likely to have an initially favourable prognosis and smaller infarcts. Also, the inherent risks of thrombolysis and the increased susceptibility of salvaged myocardium to recurrent ischaemia affect mortality subsequent to any acute reperfusion. In controlled trials, including the Western Washington Trial, no significant differences in 12-month mortalities were seen between streptokinase-and control-treated patients. In all trials, reocclusion rates and the influence of time to treatment onset must be taken into account. A sufficient sample population size is also necessary to demonstrate statistically Significant differences in effect (about 1500 patients/group). Patients most likely to benefit from thrombolysis are those at high risk treated within 3 hours. </p><p>New approaches to thrombolysis: New fibrin-specific thrombolytics include the streptokinase-plasminogen complex (SRL 26921), prourokinase, and tissue plasminogen activator (tPA). Compared with streptokinase, recominant tPA (rt-PA) is fibrin-specific, non-antigenic and rapidly effective. Results from the Thrombolysis in Myocardial Infarction trial and the European Cooperative Study indicate that IV rt-PA achieves almost twice the reperfusion rates of IV streptokinase. </p><p>Future research will employ the early use of fibrin-specific IV thrombolytics and will assess the use of PTCA or bypass surgery in patients at risk of reocclusion. Follow-up therapy with fj-blockers and calcium antagonists </p><p>2 INPHARMA 30 Aug 1986 0156-2703/86/0830-0002/0$01.00/0 ADIS Press </p></li><li><p>will be explored. Large controlled clinical trials will assess the impact of thrombolysis on post-MI morbidity and mortality. Winniford MO Cardiovascular Reviews and Reports 7 573584. Jun 1986 </p><p>50156-2703/86/0830-0003/0$01.00/0 ADIS Press INPHARMA 30 Aug 1986 3 </p><p> /ColorImageDict &gt; /JPEG2000ColorACSImageDict &gt; /JPEG2000ColorImageDict &gt; /AntiAliasGrayImages false /CropGrayImages true /GrayImageMinResolution 150 /GrayImageMinResolutionPolicy /Warning /DownsampleGrayImages true /GrayImageDownsampleType /Bicubic /GrayImageResolution 150 /GrayImageDepth -1 /GrayImageMinDownsampleDepth 2 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages true /GrayImageFilter /DCTEncode /AutoFilterGrayImages true /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict &gt; /GrayImageDict &gt; /JPEG2000GrayACSImageDict &gt; /JPEG2000GrayImageDict &gt; /AntiAliasMonoImages false /CropMonoImages true /MonoImageMinResolution 1200 /MonoImageMinResolutionPolicy /Warning /DownsampleMonoImages true /MonoImageDownsampleType /Bicubic /MonoImageResolution 600 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages true /MonoImageFilter /CCITTFaxEncode /MonoImageDict &gt; /AllowPSXObjects false /CheckCompliance [ /PDFA1B:2005 ] /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly false /PDFXNoTrimBoxError true /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox true /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile (sRGB IEC61966-2.1) /PDFXOutputConditionIdentifier () /PDFXOutputCondition () /PDFXRegistryName () /PDFXTrapped /False</p><p> /CreateJDFFile false /Description &gt;&gt;&gt; setdistillerparams&gt; setpagedevice</p></li></ul>