Concise Review for Primary-Care Physicians

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1 Concise Review for Primary-Care Physicians Acute Myocardial Infarction: Enhancing the Results of Reperfusion Therapy GUY s. REEDER, M.D. Reperfusion therapy (by either administration of thrombolytic agents or immediate angioplasty) is the mainstay of treatment of acute myocardial infarction, yet it remains underutilized. Additionally, many patients do not experience optimal reperfusion because of suboptimal flow rate in the infarct-related artery, abnormal microvascular flow, and intermittent or complete reocclusion of the infarct-related artery. Strategies to enhance the results of reperfusion therapy include expanding the population of patients considered as candidates, earlier treatment, newer methods to improve infarct-related artery flow rates, and ancillary treatments currently being studied to Reperfusion therapy with thrombolytic agents (or immediate angioplasty) is the mainstay of treatment of acute myocardial infarction. Critical components of the initial assessment of the patient with acute infarction are determination of candidacy for thrombolytic therapy and improved efficiency in its timely administration. A recent meta-analysis of the major placebo-controlled thrombolytic trials demonstrated a mean 30% relative risk reduction of mortality for patients who received a thrombolytic agent within 6 hours after onset of pain.' Despite the undeniable benefit of early reperfusion in patients with acute myocardial infarction, optimal reperfusion in such patients is probably not currently being achieved. Fewer than half of patients who have acute infarction are candidates for thrombolytic therapy (Fig. 1)Z; however, many do not receive such therapy, and many noncandidates are not referred for primary angioplasty in time to receive substantial benefit. Although a definition of optimal reperfusion is somewhat arbitrary, Lincoff and Topol' defined it as patency of the infarct-related artery with brisk, normal epicardial arterial flow, normal microvascular flow, continuous arterial patency, and the absence of vessel reocclusion early or late From the Coronary Care Unit and the Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota. Address reprint requests to Dr. G. S. Reeder, Division of Cardiovascular Diseases, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN Mayo Clin Proc 1995; 0: reduce reperfusion injury, which may be one cause of decreased microvascular flow. Although aspirin, heparin, and warfarin sodium have been the conventionally used agents for inhibiting thrombin and platelet function, newer agents such as hirudin and inhibitors of the platelet glycoprotein lib-ilia receptor are becoming available, and their clinical application will increase in the future. (Mayo Clin Proc 1995; 0: ) GUSTO =Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries; t-pa = tissue plasminogen activator after thrombolytic therapy. Unfortunately, the percentage of patients in whom thrombolytic therapy achieves the previously listed criteria is low (Fig. 2). Data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) angiographic substudy" demonstrated that with the best currently utilized thrombolytic regimen of accelerated tissue plasminogen activator (t-pa), angiographic patency of the infarct-related artery was 81% at 90 minutes; thus, effectively, in 20% of patients reperfusion was unsuccessful. In this same group, however, the presence of brisk, normal flow in the infarctrelated artery at 90 minutes was only 54%. This observation is important because in this trial, the 30-day mortality was only 4.4% in patients with normal coronary artery flow in comparison with.4% in those with mildly suboptimal flow and 8.9% in those with occlusion. This association of brisk, normal flow in the infarct-related artery with.reduced mortality has been established in three other studies>? (Table 1). Thus, even with the best thrombolytic regimen, normal flow rates in the infarct-related artery are not achieved in approximately half of patients. Further eroding the effectiveness of current reperfusion therapy is the finding by Ito and associates" that, in the presence of a reperfused vessel, 23% of patients had impaired microvascular flow as determined by contrast echocardiography. Studies utilizing continuous electrocardiographic monitoring show cyclic fluctuations of ST segments corresponding to intermittent opening and closing ofthe infarct-related Mayo Foundation for Medical Education and Research

2 1186 REPERFUSION THERAPY FOR ACUTE MYOCARDIAL INFARCTION Mayo Clio Proc, December1995, Vol 0 Too late (>6 hr) Equivocal ECG Contraindications - - r - - ~ Age >5yr Treated n=124,ooo Fig. 1. Selection of patients undergoing thrombolytic therapy for acute myocardial infarction in population of 65,000 patients. ECG = electrocardiogram. (From Muller and Topol.' By permission.) artery.' Up to one-third of patients may experience such intermittent patency, and reocclusion is likely in this group. Finally, infarct-related artery reocclusion may occur within hours or days after successful reperfusion in 5 to 13% of patients. In the GUSTO angiographic substudy,' reocclusion occurred in 5.9% of patients treated with accelerated t-pa. The adverse clinical effects of reocclusion are well confirmed. In a review of 810 patients with acute myocardial infarction treated with thrombolysis and undergoing angiography, in-hospital mortality for patients with reocclusion averaged 11% versus 4.5% (P = 0.01) for those without reocclusion.? Thus, by these criteria, perhaps as few as onethird of patients undergoing thrombolysis currently receive "optimal" reperfusion therapy. POSSIBLE STRATEGIES TO ENHANCE RESULTS OF REPERFUSION THERAPY From a practical clinical standpoint, how can the results of reperfusion therapy be enhanced? Five possible strategies are as follows: (1) expand the population of patients receiving reperfusion therapy, (2) treat patients as early as possible, (3) achieve normal flow rates in the infarct-related ar1ery (with novel thrombolytic agents or newer modes of administration of old agents or with immediate acute angioplasty) in as many patients as possible, (4) reduce occurrence ofabnormal microvascular flow (which may be a result ofreperfusion injury), and (5) decrease reocclusion. Expand the Population Eligible for Reperfusion Therapy.-Reperfusion therapy probably remains underutilized because of exclusion of elderly patients; patients who seek medical assessment late; those with diabetes mellitus, left bundle branch block, or a past central nervous system event; and those who have undergone cardiopulmonary resuscitation. Although in some situations exclusion of such patients from thrombolytic therapy may be warranted, Topol stated that "the only absolute contraindication for thrombolytic therapy is active significant bleeding.'?" All other "contraindications" are relative, and the risk resulting from thrombolysis in such patients should be weighed against the risk of mortality without thrombolytic therapy. Thus, the following groups of patients should be considered as potential thrombolytic candidates: those who have had remote nonhemorrhagic cerebrovascular events, a history of hypertension, cardiopulmonary resuscitation that was not prolonged (less than 10 minutes), diabetes including retinopathy, or bundle branch block on the initial electrocardiogram; patients of any age, including elderly patients and younger menstruating females; and those who seek medical treatment "late" (up to 12 hours after pain onset). Patients with thrombolytic contraindications and those with unrelenting chest pain and ST-segment depression (a subset in which thrombolysis has not yet been shown to affect survival) should be considered for urgent direct angioplasty. Transfer of such patients to a tertiary center that has emergency angioplasty capabilities is useful if reperfusion can be achieved in a timely manner. The continued proliferation of catheterization laboratories with urgent angioplasty capabilities allows this approach to be a real option for increasing segments of the population. Currently, however, a minority of the population still live within I hour of a center capable of performing immediate angioplasty. 90 min patency Intermittent patency m Fig. 2. Based on various criteria, percentage of patients undergoing optimal reperfusion is diminishing (see text for details). (Data from Lincoff and Topol.')

3 REPERFUSION THERAPY FOR ACUTE MYOCARDIAL INFARCTION Mayo Clio Proc, December 1995, Vol 0 Table I.-Mortality Related to Perfusion Rate* No. of Mortality] based on TIMI grade flow:j: Study patients TAMP GUST04 Vogt et al" TEAM-2 1, *TAMI = Thrombolysis and Angioplasty in Myocardial Infarction; TEAM-2 = Second Multicenter Thrombolysis Trial of Eminase in Acute Myocardial Infarction; TIMI = Thrombolysis in Myocardial Infarction; GUSTO = Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries. tto nearest percent. :j:grade3 flow is normal arterial flow. Treat Early.-That early treatment maximizes myocardial salvage and minimizes mortality is axiomatic. In the first Gruppo Italiano per 10 Studio della Streptochinasi nell'infarto Miocardico (GISSI-I) trial" and the Second International Study of Infarct Survival (ISIS-2),12 patients treated within 1 hour after onset of symptoms had a 50% relative reduction in mortality, and similar results have been found in virtually all the thrombolytic trials. In general, for every 1 hour earlier a patient receives thrombolytic therapy, a 1% reduction in absolute mortality can be expected. In the Myocardial Infarction Triage and Intervention (MIT!) trial," patients treated within 0 minutes after onset of chest pain had a mortality of 1.2% versus 8.% in those treated later. In that study, 40% of patients treated within 3 hours had no myocardial perfusion defect detectable by later tomographic thallium scanning. Very early treatment of patients may be enhanced by increased efficiencies in diagnosis and drug administration. The recent availability of rapid MB isoenzyme of creatine kinase plasma assays, with turnaround times of 20 minutes or less, as well as creatine phosphokinase isoform analysis," and other serum markers to detect early myocardial infarction will likely be commonly utilized in the future to accelerate diagnosis. (Such testing may be most useful for patients with equivocal electrocardiographic findings; patients with classic ST-segment elevation should never have treatment withheld on the basis of pending serum enzyme measurements.) Streamlining the process for procurement and administration of thrombolytic drugs or for transfer of the patient to the angiography suite is also useful in decreasing time to treatment. A "door-to-treatment time" of less than 30 minutes is a desirable goal and has been achieved for most patients at Mayo Clinic Rochester. Restore Brisk (Normal) Flow in the Infarct-Related Artery.-Multiple studies have demonstrated a strong inverse relationship between normal reperfusion flow rate and sub- 118 sequent mortality."? Although it is possible that this relationship is not causative (that is, brisk flow in the infarctrelated artery may simply be a marker for some other characteristic that confers a better prognosis), prevailing opinion suggests that a normal reperfusion flow rate should be a goal in every patient undergoing reperfusion therapy. Data from the angiographic substudy of the GUSTO trial" demonstrated the superiority of "front-loaded" t-pa versus streptokinase in achieving normal flow (54% versus 30%) at 90-minute angiography; however, even at 5 to days after infarction, normal flow rates were only 58% in the front-loaded t-pa group versus 54% in the streptokinase groups, an indication of suboptimal flow in approximately half of the treated patients. Primary angioplasty, performed in experienced centers with around-the-clock catheterization availability, seems to offer an advantage over thrombolytic therapy in terms of speed and completeness of reperfusion. In two randomized trials of primary angioplasty versus thrombolytic rherapy.p-" the mean time from evaluation to balloon inflation was approximately 60 minutes; the percentage of patients in whom early normal reperfusion flow rates were achieved was not reported. In published data from Mayo Clinic Rochester, patients experienced patency with primary angioplasty approximately one-half hour sooner than those who received thrombolytic therapy with t-p A. l Preliminary data from our catheterization laboratory suggest that normal reperfusion flow rates can be achieved in more than 80% of patients undergoing primary angioplasty in less than 90 minutes after initial assessment (Reeder GS. Unpublished data). Similar results may be obtainable with newer dosing strategies for existing thrombolytic drugs and newer thrombolytic agents (Table 2). In a study of 84 patients who sought medical assessment up to 6 hours after onset of acute Q-wave myocardial infarction and in whom 100 mg oft-pa was administered as two intravenous bolus injections (50 mg each given 30 minutes apart), normal reperfusion flow rates were achieved in 86% at 60 minutes and 88% at 90 minutes." No cerebrovascular bleeding occurred. In preliminary investigations of two newer agents being studied, recombinant plasminogen activator and staphlokinase, a fibrin-specific agent, both have demonstrated normal reperfusion flow rates in 60 to 0% of patients at 90-minute angiography. Trials of newer agents and more effective dosing strategies are ongoing. Prevent Reperfusion Injury.--Qf the many types'? of reperfusion injury documented with animal models, two varieties probably occur in humans: microvascular damage and stunned myocardium. Microvascular damage may lead to the "no-reflow phenomenon" demonstrated by Ito and others," in which flow remains sluggish due to poor myocardial perfusion at the microvascular level despite restoration

4 1188 REPERFUSION THERAPY FOR ACUTE MYOCARDIAL INFARCTION Mayo Clio Proc, December 1995, Vol 0 Table 2.-Administration of Thrombolytic Agents* 90 minutes Patency TIMI 3 flow Agent Dosage (0/0) (0/0) Streptokinase 1.5 million U/h 5 30 t-pa 100 mg during 3 h 1 52 Accelerated t-pa 100 mg during 90 min Double-bolus t-pat 50-mg bolus given twice 30 min apart Staphlokinaset:j: 20 mg during 30 min 83 0 *TIMI = Thrombolysis in Myocardial Infarction; t-pa = tissue plasminogen activator. [Considered investigational. :j:van de WerfFJ. Presented at the American Heart Association meeting; 1994 Nov 14-1; Dallas (TX). of wide patency of the infarct-related artery. With myocardial stunning, contractile dysfunction of viable myocardium occurs and may persist for hours to days after reperfusion. The "early hazard function"-the fact that, within the first 24 hours after administration of thrombolytic agents, mortality is higher in the thrombolytic group than in the control group-has been postulated to be partly related to these types of reperfusioninjury. 19,20 Becausefree oxygen radicals may be produced as a result of ischemia, several studies have examined the results of administering oxygen radical scavengers, antioxidants, iron chelaters, and Fluosol, a synthetic oxygen-carrying substance. Unfortunately, no beneficial results have been reported; however, a combinationof intravenous adenosine and lidocaine has been shown to limit infarct size in experimental canine myocardial infarction." Salutary effects of adenosine might include reducedgranulocyte adhesion, decreasedfree oxygen radical production, and enhanced local collateral flow, as well as acting as a substrate for re-formation of high-energy phosphate compounds. Studies using adenosine and lidocaine in conjunction with thrombolysis and primary angioplasty are ongoing. Decrease Reocclusion.-The problems of intermittent patency and its role as a marker for infarct-related artery reocclusion, as well as the deleterious effects of reocclusion, have been previously discussed.' Aspirin irreversibly inhibits platelet cyclooxygenase, and its value in adequate doses in conjunction with streptokinase has been firmly established,'? probably by reducing platelet-mediated early reocclusion. The role of heparin in reducing early reocclusion is thought to be most important with t-pa (its additional value in patients taking streptokinase or other nonselective agents is less certain)." Unfortunately, reocclusion may still occur despite appropriate administration of these agents, a suggestionof the need for more potent antiplatelet and antithrombin agents. The final common pathway of platelet aggregation involves the glycoprotein Ilb-Illa platelet receptor. Both antibody and nonantibody (peptide) inhibitors of this receptor are or will soon be available for clinical use, including the monoclonal antibody E3, the synthetic heptapeptide integrelin (COR Therapeutics, Inc., South San Francisco, California), and the nonantibody agent MK-383 (Merck Research Laboratories). In the Evaluation of E3 for the Prevention of Ischemic Complications (EPIC) trial," adjunctive use of E3 at the time of angioplasty yielded reduced rates of acute reocclusion. Further studies with these agents for acute infarction are ongoing. More complete thrombin inhibition has been postulated as another means of reducing reocclusion. Heparin, an indirect thrombin inhibitor, acts primarily through antithrombin 3 and is ineffective against clot-bound thrombin. Hirudin, a substance derived from the saliva of the medicinal leech and available in recombinant form, is a direct inhibitor of thrombin and is effective against clot-bound thrombin as well. This more potent agent has been preliminarily tested in three published trials involving thrombolytic therapy for acute coronary syndromes.s':" Unfortunately, these trials were discontinued prematurely because of an increased incidence of intracranial bleeding in both the hirudin and control (heparin) groups. The trials have been restarted, however, with a lower dose of hirudin; data on relative rates of reocclusion are currently unavailable. In theory, immediate angioplasty or other mechanical intervention in the occluded infarct-related artery (by removal of the high-grade residual stenosis often present after thrombolysis) might be expected to reduce the incidence of reocclusion. Ofthe three major randomized trials of primary angioplasty versus thrombolytic therapy, two trials suggest that this might be the case. In the Primary Angioplasty in Myocardial Infarction trial," the combined endpoint, death and recurrent myocardial infarction, occurred significantly less frequently in patients treated with primary angioplasty than in those given thrombolysis with t-pa. In the Nether-

5 Mayo Clio Proc, December 1995, Vol 0 REPERFUSION THERAPY FOR ACUTE MYOCARDIAL INFARCTION lands study, 16 a comparison of primary angioplasty and intravenous thrombolysis therapy with streptokinase, late arterial patency was significantly higher in the primary angioplasty group. In none of these studies, however, was the direct comparison of reocclusion established between the two treatment groups, and it seems unlikely that rates lower than 5 to 6%, as found in the recent GUSTO trial, will be achieved with any mechanical intervention. Predicting which patients will experience reocclusion is also problematic. Although continuous 12-lead electrocardiographic monitoring may demonstrate intermittent patency as a risk factor for reocclusion, no other clinical or angiographic variables are predictive. In fact, at least four studies now demonstrate that angiographic features of the recently reperfused infarct-related artery are not useful in predicting those patients who will experience reocclusion. 2-3o A recent report by Ohman and associates" suggests that, in patients undergoing angioplasty for acute infarction, empiric intra-aortic balloon pumping can reduce the risk of immediate closure after angioplasty CONCLUSION In many patients undergoing reperfusion therapy for acute infarction, optimal reperfusion is probably not achieved. A practical approach to enhance the results of reperfusion therapies includes expanding the population eligible for reperfusion therapy, earlier treatment, continued development of strategies to achieve brisk, normal flow rates in the infarct-related artery, prevention of reperfusion injury, and decreasing reocclusion of the infarct-related artery. In the future, further refinement in the use of existing thrombolytic agents, newer thrombolytics, an expanded role for primary angioplasty, and the use of newer agents for thrombin and platelet inhibition will likely help achieve this goal REFERENCES 1. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994; 343: Muller DW, Topol EJ. Selection of patients with acute myocardial infarction for thrombolytic therapy. Ann Intern Med 1990; 113: Lincoff AM, Topol EJ. Illusion ofreperfusion: does anyone achieve optimal reperfusion during acute myocardial infarction? Circulation 1993; 8: GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronaryartery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993; 329: Lincoff AM, Topol EJ. Trickle down thrombolysis [editorial]. J Am Coli Cardiol 1993; 21: Vogt A, von Essen R, Tebbe U, Feuerer W, Appel KF, Neuhaus KL. Impact of early perfusion status of the infarctrelated artery on short-term mortality after thrombolysis for 1., acute myocardial infarction: retrospective analysis of four German multicenter studies. J Am Coil Cardiol 1993; 21: Karagounis L, Sorensen SG, Menlove RL, Moreno F, Anderson JL. Does thrombolysis in myocardial infarction (TIMI) perfusion grade 2 represent a mostly patent artery or a mostly occluded artery? Enzymatic and electrocardiographic evidence from the TEAM-2 study: Second Multicenter Thrombolysis Trial of Eminase in Acute Myocardial Infarction. 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Lancet 1988; 2: Weaver WD, Cerqueira M, Hallstrom AP, Litwin PE, Martin JS, Kudenchuck PJ, et al (for the Myocardial Infarction Triage and Intervention Project Group). Prehospital-initiated vs hospital-initiated thrombolytic therapy: the Myocardial Infarction Triage and Intervention Trial. JAMA 1993; 20: Reeder GS, Gersh BJ. Modem management of acute myocardial infarction. CUff Probl Cardiol 1993; 18: Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O'Keefe J, et al (for the Primary Angioplasty in Myocardial Infarction Study Group). A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993; 328:63-69 Zijlstra F, de Boer MJ, Hoomtje JCA, Reiffers S, Reiber JHC, Suryapranata H. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993; 328: Berger PB, Bell MR, Holmes DR Jr, Gersh BJ, Hopfenspirger M, Gibbons R. Time to reperfusion with direct coronary angioplasty and thrombolytic therapy in acute myocardial infarction. Am J Cardiol 1994; 3: Purvis JA, McNeill AJ, Siddiqui RA, Roberts MJ, McClements BM, McEneaney D, et al. Efficacy of 100mg of double-bolus alteplase in achieving complete perfusion in the treatment of acute myocardial infarction. J Am Coil Cardiol 1994; 23:6-10 Kloner RA. Does reperfusion injury exist in humans? JAm Coli Cardiol 1993; 21: Ohman EM, Topol EJ, Califf RM, Bates ER, Ellis SG, Kereiakes DJ, et al. An analysis of the cause of early mortality after administration of thrombolytic therapy: the Thrombolysis Angioplasty in Myocardial Infarction Study Group. Coron Artery Dis 1993; 4: Forman MB, Velasco CE, Jackson EK. Adenosine attenuates reperfusion injury following regional myocardial ischaemia. Cardiovasc Res 1993; 2:9-1

6 1190 REPERFUSION THERAPY FOR ACUTE MYOCARDIAL INFARCTION Mayo Clin Proc, December 1995, Vol SCA TI (Studio sulla Calciparina nell'angina e nella Trombosi Ventricolare nell'infarto) Group. Randomised controlled trial of subcutaneous calcium-heparin in acute myocardial infarction. Lancet 1989; 2: EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994; 330: Neuhaus KL, von Essen R, Tebbe U, Jessel A, Heinrichs H, Maurer W, et al. Safety observations from the pilot phase of the randomized r-hirudin for Improvement of Thrombolysis (HIT-III) study: a study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausarzte (ALKK). Circulation 1994; 90: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIa Investigators. Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation 1994; 90: Antman EM (for the TIMI 9A Investigators). Hirudin in acute myocardial infarction: safety report from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIM!) 9A trial. Circulation 1994; 90: Reiner JS, Lundergan CF, van den Brand M, Boland J, Thompson MA, Machecourt J, et al (for the GUSTO Angiographic Investigators). Early angiography cannot predict postthrombolytic coronary reocclusion: observations from the GUSTO angiographic study. J Am Coli Cardiol 1994; 24: Rogers WJ, Bairn OS, Gore JM, Brown BG, Roberts R, Williams DO, et al. Comparison of immediate invasive, delayed invasive, and conservative strategies after tissue-type plasminogen activator: results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II-A trial. Circulation 1990; 81: SWIFf (Should We Intervene Following Thrombolysis?) Trial Study Group. SWIFf trial of delayed elective intervention v conservative treatment after thrombolysis with anistreplase in acute myocardial infarction. BMJ 1991; 302: Topol EJ, CaliffRM, George BS, Kereiakes OJ, Abbottsmith CW, Candela RJ, et al. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. N Engl J Med 198; 31: Ohman EM, George BS, White CJ, Kern MJ, Gurbel PA, Freedman RJ, et al (for the Randomized IABP Study Group). Use of aortic counterpulsation to improve sustained coronary artery patency during acute myocardial infarction: results of a randomized trial. Circulation 1994; 90:92-99 Questions About Reperfusion Therapy for Acute Myocardial Infarction (See article, pages 1185 to 1190) 1. Which one of the following "time periods," with regard to a "door-to-needle time," should not be exceeded in patients receiving thrombolytic therapy for acute myocardial infarction? a. 2 hours b. 1 hour c. 30 minutes d. IO minutes e. 5 minutes 2. Which one of the following numbers (representing expected percent reduction in absolute mortality for every hour of delay eliminated) is correct regarding early treatment of acute myocardial infarction? a. 0.1 b. I c. IO d.50 e Which one of the following patient characteristics is a contraindication to thrombolytic therapy? a. Active menstruation b. Age older than 80 years c. Left bundle branch block d. Duration of pain-io hours e. Evidence of active gastrointestinal bleeding 4. In which one of the following patient groups is primary angioplasty (without thrombolytic therapy) not an alternative to thrombolytic therapy? a. Patients with cardiogenic shock b. Patients with thrombolytic contraindications c. Any patient if a catheterization laboratory and an experienced team are immediately available d. Selected patients with continuing pain and ST-segment depression e. Patients who can be transferred to an angioplasty center within 4 hours after initial assessment 5. Which one of the following statements is incorrect regarding thrombolytic agents? a. Newer thrombolytic agents with fibrin specificity include recombinant plasminogen activator and staphlokinase b. Double-bolus administration of tissue plasminogen activator (t-pa) may result in higher flow rates in the infarct-related artery c. Streptokinase and t-pa produce equal degrees of reperfusion and flow rates in the infarct-related artery d. Hirudin is a newer, direct-acting antithrombin e. E3 is a newer type of platelet inhibitor Correct answers: