81st (Spring) Meeting of Ulster Society of Internal Medicine, Friday 15th May 2009 Medical Education Centre, Craigavon Hospital, Portadown

Between 1986 and 1988, 239 consecutive patients with acute myocardial infarction received thrombolytic therapy up to 285 minutes after onset of symptoms; in 39 (17 with anterior infarction, 21 inferior, one lateral infarction) recombinant tissue plasminogen activator or anistreplase was administered a mean of 51 minutes (range 20-60 minutes) after the onset of symptoms. The patency rates (26 of 30; 87 per cent), rapid ST segment resolution (36 of 38; 95 per cent) and QRS score of less than or equal to 3 (28 of 38; 74 per cent) were statistically significantly higher for those seen and treated in the first hour in comparison with those seen and treated later. For those treated within the first hour mean peak creatine kinase was 1264 U/l for those with TIMI grade 2 or 3 (partial or complete perfusion) compared with 3005 U/l for those with TIMI grade 0 or 1 (no perfusion or penetration without perfusion) (p = 0.02): mean peak creatine kinase-MB for those with TIMI grade 2 or 3 perfusion was 115 U/l compared with 312 U/l for those with TIMI grade 0 or 1 (p = 0.01). Four of the 39 patients developed ventricular fibrillation following thrombolytic therapy, three within 24 hours of infarction and one following reinfarction on day 15. There were no significant bleeding complications. One patient died. Thrombolytic therapy within 1 hour of the onset of symptoms led to a very high angiographic patency rate, rapid ST segment resolution with preservation of left ventricular function. This therapy is without significant complications.

Of consecutive patients seen with first myocardial infarction (88 of whom were treated out-of-hospital by mobile coronary care staff), 139 received 30 units of intravenous anistreplase at a mean of 101 minutes (range 35-180) from onset of symptoms. Thrombolysis in myocardial infarction patency grade 2 or 3 was found in 76/91 (83.5%) patients. At 3-4 months after hospital discharge, the mean global left ventricular ejection fraction and mean infarct-related regional third ejection fraction declined with increasing delay to anistreplase. For the first, second and third hour administrations, global ejection fraction was 54%, 50% and 45% (P = 0.002) and for regional third ejection fractions 49%, 43% and 41% (P = 0.02) respectively.Of the patients, 130 were reviewed at approximately 1 year: reinfarction had occurred in 9, 6 had undergone coronary angioplasty and 1 had coronary arterial bypass grafting performed since discharge. Mean global left ventricular ejection fraction was 52% and mean infarct-related regional third ejection fraction was 51%.Thus, intravenous anistreplase induces high rates of arterial patency. Global and regional third ejection fractions decline with increasing delay in the time of administration of anistreplase. Mortality and morbidity is low in the first year.

Within four hours of the onset of acute myocardial infarction 57 consecutive patients were randomised blindly to infusion of 150 mg recombinant tissue plasminogen activator (rt-PA) (group 1) over five hours or placebo (group 2) when they were first seen outside hospital or in the accident and emergency department. When they were admitted to the coronary care unit patients in group 1 also had placebo infused and those in group 2 were treated with rt-PA as well as placebo. Treatment with rt-PA started at a mean of 119 minutes (range 38-235) after the onset of pain in group 1 and 187 minutes (range 80-285) after the onset of pain in group. In 19 (79%) of 24 in group 1 and 16 of 25 (64%) in group 2 cardiac catheterisation 10-14 days after infarction showed thrombolysis in myocardial infarction grades 2 or 3. There was mean percentage shortening of the infarct related segments (Leighton method) of 16% in group 1 and 10.3% in group 2. For patients with anterior infarction mean percentage shortening was 20.5% in group 1 and 12.2% in group 2. Although there was no significant difference in global ejection fraction as assessed by contrast ventriculography or radionuclide ventriculography the infarct related regional third ejection fraction (a measure of the function of the territory of the affected coronary artery) was significantly improved by early treatment (41% group 1 and 28% group 2). Assessment of infarct size by the QRS scoring method of Palmeri showed QRS score less than or equal to 15/25 patients in group 1 and 8/27 in group 2. Nine patients developed 11 episodes of ventricular fibrillation; all patients in whom ventricular fibrillation developed during treatment with rt-PA were successfully resuscitated. There was no clinically significant bleeding. In seven (12%) patients clinical and electrocardiographic criteria suggested reocclusion. Five patients died from cardiac causes. Prehospital administration of rt-PA was feasible and significantly reduced the delay before thrombolysis was started. Earlier treatment improved myocardial function in the the infarct area and reduced the infarct size.

To assess the thrombolytic efficacy and the effect on the systemic fibrinolytic system of recombinant tissue plasminogen activator doses of 20 mg, 50 mg, and 100 mg were compared in a randomised study. Tissue plasminogen activator was infused intravenously over 90 minutes in 50 consecutive patients with acute myocardial infarction of four hours' duration or less; on average the infusion was started 135 minutes (range 20 to 240) after the onset of pain. The affected artery was patent at the end of the 90 minute infusion in 14/17 (82%) of those who received 100 mg, 12/17 (71%) of those who received 50 mg, and 8/16 (50%) of those who received 20 mg. Regardless of dose, reperfusion rates were significantly better for patients treated within two hours of the onset of symptoms (81%) than for those treated in the third and fourth hours (54%). At the end of the infusion serum fibrinogen concentrations fell to 86% of the preinfusion value after 20 mg, 75% after 50 mg, and 63% after 100 mg, and similar dose dependent changes occurred in plasminogen, (alpha 2 anti-plasmin, and fibrinogen and fibrin degradation products. The mean infarct related regional third ejection fraction was 46% for patients with grade 2 or 3 reperfusion and 35% for those with grade 0 or 1. Ventricular fibrillation occurred in six (12%) patients during the infusion of tissue plasminogen activator, but no late ventricular fibrillation occurred. Bleeding was minimal, reocclusion occurred in three patients, and four patients died from cardiac causes. Recombinant tissue plasminogen activator is an effective thrombolytic agent which produces better reperfusion rates after a 50 or 100 mg dose than after a 20 mg dose. The effect on the systemic fibrinolytic system is dose dependent. Successful reperfusion results in improvement of left ventricular function.