Thrombolysis in MI ================== þ Don't give thrombolytics to those over 80 with MI. - Those over 80, even with no contraindications, have a 40% increased mortality if given thrombolytics. [Arch Intern Med 2002;161:561-568.] "Among all the patients who received thrombolytic therapy, there was a 4% increase in the odds of death for every 1-year increase in age (odds ratio 1.04, p = 0.03). For patients who had one or more contraindications to thrombolytic therapy, the risk of death was further increased (odds ratio 1.57, p = 0.04), Dr. Soumerai's team notes. Compared with patients who did not receive thrombolytic therapy, patients who did receive thrombolytic therapy were at a significantly increased risk for death with age (adjusted odds ratio 1.08 per year, p = 0.008)." þ Combination Therapy: low-dose thrombolytics + platelet inhibitor 50 mg of alteplase (15-mg bolus; infusion of 35 mg over 60 minutes) + Reopro or Integrelin followed by LOW-DOSE heparin (? LMWH) Antman EM, Giugliano RP, Gibson CM, et al. Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators Circulation 1999; 99 2720-32 BACKGROUND: The TIMI 14 trial tested the hypothesis that abciximab, the Fab fragment of a monoclonal antibody directed to the platelet glycoprotein (GP) IIb/IIIa receptor, is a potent and safe addition to reduced-dose thrombolytic regimens for ST-segment elevation MI. METHODS AND RESULTS: Patients (n=888) with ST-elevation MI presenting 12 hours from onset of symptoms were treated with aspirin and randomized initially to either 100 mg of accelerated-dose alteplase (control) or abciximab (bolus 0.25 mg/kg and 12-hour infusion of 0.125 microg. kg-1. min-1) alone or in combination with reduced doses of alteplase (20 to 65 mg) or streptokinase (500 000 U to 1.5 MU). Control patients received standard weight-adjusted heparin (70-U/kg bolus; infusion of 15 U. kg-1. h-1), whereas those treated with a regimen including abciximab received low-dose heparin (60-U/kg bolus; infusion of 7 U. kg- 1. h-1). The rate of TIMI 3 flow at 90 minutes for patients treated with accelerated alteplase alone was 57% compared with 32% for abciximab alone and 34% to 46% for doses of streptokinase between 500 000 U and 1.25 MU with abciximab. Higher rates of TIMI 3 flow at both 60 and 90 minutes were observed with increasing duration of administration of alteplase, progressing from a bolus alone to a bolus followed by either a 30- or 60-minute infusion (P0.02). The most promising regimen was 50 mg of alteplase (15-mg bolus; infusion of 35 mg over 60 minutes), which produced a 76% rate of TIMI 3 flow at 90 minutes and was tested subsequently in conjunction with either low-dose or very-low-dose (30-U/kg bolus; infusion of 4 U. kg-1. h-1) heparin. TIMI 3 flow rates were significantly higher in the 50-mg alteplase plus abciximab group versus the alteplase-only group at both 60 minutes (72% versus 43%; P=0.0009) and 90 minutes (77% versus 62%; P=0.02). The rates of major hemorrhage were 6% in patients receiving alteplase alone (n=235), 3% with abciximab alone (n=32), 10% with streptokinase plus abciximab (n=143), 7% with 50 mg of alteplase plus abciximab and low- dose heparin (n=103), and 1% with 50 mg of alteplase plus abciximab with very-low-dose heparin (n=70). CONCLUSIONS: Abciximab facilitates the rate and extent of thrombolysis, producing early, marked increases in TIMI 3 flow when combined with half the usual dose of alteplase. This improvement in reperfusion with alteplase occurred without an increase in the risk of major bleeding. Substantial reductions in heparin dosing may reduce the risk of bleeding even further. Modest improvements in TIMI 3 flow were seen when abciximab was combined with streptokinase, but there was an increased risk of bleeding. þ Should one add heparin to aspirin, with or without thrombolysis? - this analysis says no [Collins R., et al. Clinical effects of anticoagulant therapy in suspected acute MI: systematic overview of ransomised trials. Br J Med 1996;313(7058):652.] Mercy Hospital Protocols Thrombolysis vs. PTCA for MI Trials: þ ASSET: Anglo-Scandinavian Study of Early Thrombolysis þ DUCCS I: Duke University Clinical Cardiology Studies þ ECSG: European Cooperative Study Group þ EMIP: þ GISSI-1: Gruppo Italiano de lo Studio della Streptochinasi nell'Infarto Miocardico þ GISSI-2: þ GUSTO: Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries þ GUSTO II: þ HART: Heparin-Aspirin Reperfusion Trial þ ISIS-2: Second International Study of Infarct Survival þ ISIS-3: Third International Study of Infarct Survival þ ISIS-4: Fourth International Study of Infarct Survival þ LATE: Late Assessment of Thrombolytic thErapy þ MITI: Myocardial Infarction Triage and Intervention þ TIMI-IIB: Thrombolysis in MI #2 þ Should you wait for a CXR to rule out dissection before giving tPA? - yes. [Butler et. al. Streptokinase in Aortic Dissection. BMJ 1990;300:517-19.] - no. [Hartnell GG, Wakeley CJ, Tottle A, Papouchado M, Wilde RP Limitations of chest radiography in discriminating between aortic dissection and myocardial infarction: implications for thrombolysis. J Thorac Imaging 1993 Spring;8(2):152-5.] Abstract: þ Choice of tPA vs. Strepto þ Does NTG interfere with TPA? - What do you do with a patient who is getting thrombolytics, is on a NTG drip, whose BP is down to 120 systolic, and is still having pain? The NTG drip may be interfering with thrombolysis. The authors of these two small studies suggest that NTG interferes with the action of tPA, presumably by promoting blood flow to the liver and enhancing catabolism of tPA. (I, myself have the perhaps naive opinion that thrombolysis is like clearing a plugged toilet--the Draino works better if you're pumping harder on the plunger--up to a limit: you don't want to burst the pipes!) You have already made the diagnosis of MI, the patient is (presumably) being closely monitored, so what harm is there in "masking" the pain? In my experience it takes relatively small doses of morphine (5 mg) to make the patient more comfortable, and the patients can still tell you when they start to feel worse. I also find that the patient's BP is less likely to drop with a small dose of morphine than with increasing the NTG. [Nicolini. FA, et al. Concurrent nitroglycerin therapy impairs tissue-type plasminogen activator-induced thrombolysis in patients with acute myocardial infarction. Am J Cardiol 1994;74(7):662.] Abstract: [Romeo F, et al. Concurrent nitroglycerin administration reduces the efficacy of recombinant tissue-type plasminogen activator in patients with acute anterior wall myocardial infarction. Am Heart J 1995; 130(4):692.] Abstract: