Candidates For Thrombolytic Therapy Research Articles

A randomized trial of the effects of early cardiac serum marker availability on reperfusion therapy in patients with acute myocardial infarction: The serial markers, acute myocardial infarction and rapid treatment trial (SMARTT)

OBJECTIVESThe purpose of this study was to assess whether the immediate availability of serum markers would increase the appropriate use of thrombolytic therapy.BACKGROUNDSerum markers such as myoglobin and creatine kinase, MB fraction (CK-MB) are effective in detecting acute myocardial infarction (AMI) in the emergency setting. Appropriate candidates for thrombolytic therapy are not always identified in the emergency department (ED), as 20% to 30% of eligible patients go untreated, representing 10% to 15% of all patients with AMI. Patients presenting with chest pain consistent with acute coronary syndrome were evaluated in the EDs of 12 hospitals throughout North America.METHODSIn this randomized, controlled clinical trial, physicians received either the immediate myoglobin/CK-MB results at 0 and 1 h after enrollment (stat) or conventional reporting of myoglobin/CK-MB 3 h or more after hospital admission (control). The primary end point was the comparison of the proportion of patients within the stat group versus control group who received appropriate thrombolytic therapy. Secondary end points included the emergent use of any reperfusion treatment in both groups, initial hospital disposition of patients (coronary care unit, monitor or nonmonitor beds) and the proportion of patients appropriately discharged from the ED.RESULTSOf 6,352 patients enrolled, 814 (12.8%) were diagnosed as having AMI. For patients having AMI, there were no statistically significant differences in the proportion of patients treated with thrombolytic therapy between the stat and control groups (15.1% vs. 17.1%, p = 0.45). When only patients with ST segment elevation on their initial electrocardiogram were compared, there were still no significant differences between the groups. Also, there was no difference in the hospital placement of patients in critical care and non–critical care beds. The availability of early markers was associated with more hospital admissions as compared to the control group, as the number of patients discharged from the ED was decreased in the stat versus control groups (28.4% vs. 31.5%, p = 0.023).CONCLUSIONSThe availability of 0- and 1-h myoglobin and CK-MB results after ED evaluation had no effect on the use of thrombolytic therapy for patients presenting with AMI, and it slightly increased the number of patients admitted to the hospital who had no evidence of acute myocardial necrosis.

Should antihypertensive therapies be given to patients with acute ischemic stroke?

Hypertension is a major risk factor for stroke and many patients with acute stroke have elevated blood pressures. The management of hypertension in the setting of acute ischaemic stroke remains a source of confusion and controversy. Lowering blood pressure in this setting may be hazardous because of impaired cerebral autoregulation. Treatment may be considered in patients who are otherwise candidates for thrombolytic therapy, patients who have severe hypertension or patients who have specific concomitant medical conditions including acute myocardial infarction, aortic dissection, hypertensive encephalopathy, or severe left ventricular failure. In choosing an agent for acute treatment, drugs that can produce a precipitous decline in blood pressure (e.g. sublingual calcium antagonists) should be avoided. Drugs with the capacity to dilate cerebral vessels should be used with caution as they have the potential to increase intracranial pressure. Long term management of hypertension in poststroke patients is often required. The potential for certain classes of drugs (e.g. alpha2-adrenergic receptor agonists and alpha1-adrenergic receptor antagonists) to impair the recovery process should be considered when choosing an antihypertensive for treatment of these patients.

Cincinnati Prehospital Stroke Scale: Reproducibility and Validity

Study objective: The Cincinnati Prehospital Stroke Scale (CPSS) is a 3-item scale based on a simplification of the National Institutes of Health (NIH) Stroke Scale. When performed by a physician, it has a high sensitivity and specificity in identifying patients with stroke who are candidates for thrombolysis. The objective of this study was to validate and verify the reproducibility of the CPSS when used by prehospital providers. Methods: The CPSS was performed and scored by a physician certified in the use of the NIH Stroke Scale (gold standard). Simultaneously, a group of 4 paramedics and EMTs scored the same patient. Results: A total of 860 scales were completed on a convenience sample of 171 patients from the emergency department and neurology inpatient service. Of these patients, 49 had a diagnosis of stroke or transient ischemic attack. High reproducibility was observed among prehospital providers for total score (intraclass correlation coefficient [r I], .89; 95% confidence interval [CI], .87 to .92) and for each scale item: arm weakness, speech, and facial droop (.91, .84, and .75, respectively). There was excellent intraclass correlation between the physician and the prehospital providers for total score (r I, .92; 95% CI, .89 to .93) and for the specific items of the scale (.91, .87, and .78, respectively). Observation by the physician of an abnormality in any 1 of the 3 stroke scale items had a sensitivity of 66% and specificity of 87% in identifying a stroke patient. The sensitivity was 88% for identification of patients with anterior circulation strokes. Conclusion: The CPSS has excellent reproducibility among prehospital personnel and physicians. It has good validity in identifying patients with stroke who are candidates for thrombolytic therapy, especially those with anterior circulation stroke. [Kothari RU, Pancioli A, Liu T, Brott T, Broderick J: Cincinnati Prehospital Stroke Scale: Reproducibility and validity. Ann Emerg Med April 1999;33:373-378.]

Non-Valvular Atrial Fibrillation in Acute Ischaemic Stroke Candidates for Thrombolytic Therapy

Non-Valvular Atrial Fibrillation in Acute Ischaemic Stroke Candidates for Thrombolytic Therapy

A cost-effectiveness model of thrombolytic therapy for acute myocardial infarction

To assess the short- and long-term costs and clinical and quality of life outcomes with the use of streptokinase (SK) vs tissue plasminogen activator (tPA) for acute myocardial infarction (MI). A decision analysis model. Patients with acute MI who were candidates for thrombolytic therapy and who presented within six hours of symptom onset. 30-day and one-year mortality, impacts of disabling and nondisabling stroke, reinfarction, hemorrhage, hypotension, anaphylaxis, and long-term medical costs. Using 30-day mortality data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, the baseline analysis yielded an incremental cost-effectiveness for tPA of $30,300 per additional quality-adjusted life year (QALY) gained, compared with SK. Using one-year mortality data from the GUSTO trial, the analysis yielded an incremental cost-effectiveness for tPA of $27,400 per additional QALY, compared with SK. The incremental cost-effectiveness of tPA over SK was sensitive to the difference in mortality seen with the two agents, exceeding $100,000 per QALY, for a relative survival advantage of approximately one-third that seen in the GUSTO trial. The incremental cost per QALY of tPA remained under $60,000 if the survival benefit was half that seen in the GUSTO trial. The cost-effectiveness of tPA declined with a shorter projected life expectancy following MI and for inferior (vs anterior) wall infarction. The analysis was modestly sensitive to the costs of the thrombolytic agents. In spite of its higher cost relative to SK, tPA is a cost-effective therapy for MI under a wide range of assumptions regarding clinical outcomes and costs.

A population-based assessment of the use and effectiveness of thrombolytic therapy: The Corpus Christi Heart Project

Little is known regarding the use and effectiveness of thrombolytic therapy in community settings, especially regarding the receipt of therapy by Mexican Americans. Thus, we examined the factors associated with receipt of thrombolysis and the survival experience of recipients and nonrecipients in the Corpus Christi Heart Project. The Corpus Christi Heart Project is a population-based surveillance program for hospitalized myocardial infarction among Mexican-American and non-Hispanic white women and men residing in Corpus Christi, Texas. Multivariate regression analyses were used to identify factors associated with receipt of thrombolytic therapy and to assess the association between receipt of thrombolytic therapy and mortality. During a 2-year period, 1199 patients hospitalized for myocardial infarction were identified; 159 (13.3%) received thrombolysis. Among “ideal” candidates for thrombolytic therapy, 74 (35.1%) of 211 received such therapy. Women were less likely to receive thrombolysis than men, and Mexican Americans were less likely to received thrombolysis than non-Hispanic whites. Patients for whom there was a delay of more than 4 hours between onset of symptoms and arrival at the hospital were also less likely to receive thrombolysis. Recipients of thrombolytic therapy experienced lower mortality over 56 months following myocardial infarction than did nonrecipients (20.5 versus 33.2%, P < 0.01). Use of thrombolytic therapy was less frequent among women and Mexican Americans than among men and non-Hispanic whites, and was limited by delay between onset of symptoms and arrival at the hospital. Given the apparent benefit of thrombolysis, interventions should be designed to educate physicians regarding the need to make this therapy available to all appropriate patients with myocardial infarction regardless of sex or ethnicity and to educate the public to reduce the delay in seeking health care after the onset of cardiac symptoms.

956-117 Eligibility for Thrombolytic Therapy is Limited Even with Expanded Criteria

Thrombolytic therapy (TT) clearly saves lives in acute myocardial infarction (MI), but the major limitation to its widespread use has been the large proportion of MI pts considered ineligible for TT. In recent overviews of the large randomized TT trials, net benefit is consistently seen with: 1) ST elevation MI (diagnostic ST elevations in any anatomic location) or left bundle branch block on presenting ECG; 2) any age; and 3) onset of symptoms &lt; 12 hrs. To describe correlates of TT utilization and to determine the potential impact of recently expanded TT criteria on the number of untreated pts, we studied 292 pts with acute MI who were admitted via the Emergency Department between June 1991 and December 1992 into a large university teaching hospital. 222 (76%) did not receive TT. Univariate correlates of TT utilization:Empty CellTI (n = 70)NoTT (n = 222)p-valueST elevation MI (n = 94):5143&lt; 0.0001Age ≥ 75 yrs (n = 78):771&lt; 0.001Onset ≤ 12 hrs (n = 163):56107&lt; 0.0001Chronic angina (n = 114):1698&lt; 0.01Chronic CHF (n = 51):348&lt; 0.001Prior MI (n = 108):1494&lt; 0.001Hospital death (n = 28):226&lt; 0.05 The most common reason for not treating with TT was absence of criteria for ST elevation MI in 179/222 pts (81%). Of 35/222 (16%) who presented between 4–12 hrs, age or duration of symptoms was the sole contraindication to TT in only 8 (4%). Other less common major contraindications to TT included prolonged chest massage, recent surgery, active internal bleeding, and hemodynamic instability. 1) Most pts did not receive TT. 2) Even with expanded treatment criteria, few additional pts become candidates for TT. 3) Future research should focus on the majority of the MI population which fails to meet ECG or other TT criteria.

Magnesium therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy

Thrombolytic therapy reduces in-hospital mortality. However, 70% to 80% of patients do not receive thrombolysis and their in-hospital mortality is high. During the last decade some clinical trials demonstrated that magnesium sulfate reduced in-hospital mortality. The aim of this study was to evaluate the effects of magnesium sulfate in patients with acute myocardial infarction (AMI) who were considered unsuitable for thrombolytic therapy. Intravenous magnesium sulfate was evaluated in 194 patients with AMI ineligible for thrombolytic therapy in a randomized, double-blind, placebo-controlled study. Group I consisted of 96 patients who received 48-hour intravenous magnesium. Group II consisted of 98 patients who received isotonic glucose as a placebo. Magnesium reduced the incidence of arrhythmias, congestive heart failure, and conduction disturbances compared with placebo (27% vs 40%, p = 0.04; 18% vs 23%, p = 0.27; 10% vs 15%, p = 0.21, respectively). Left ventricular ejection fraction 72 hours and 1 to 2 months after admission was higher in patients who received magnesium sulfate than in those taking placebo (49% vs 43% and 52% vs 45%; p = 0.01, respectively). In-hospital mortality was significantly reduced in patients receiving magnesium sulfate than in those receiving placebo (4% vs 17%; p < 0.01), and also in the subgroup of elderly patients (>70 years) (9% vs 23%; p = 0.09). In conclusion, magnesium sulfate should be considered as an alternative therapy to thrombolysis in patients with AMI.

Direct Comparison of Aspirin Plus Hirudin, Aspirin Plus Heparin, and Aspirin Alone Among 12,000 Patients with Acute Myocardial Infarction Not Receiving Thrombolysis: Rationale and Design of the First American Study of Infarct Survival (ASIS-1).

While antithrombotic therapy of acute myocardial infarction is clearly beneficial, substantial controversy exists regarding the optimal regimen. In particular, while aspirin alone has proven highly effective in reducing rates of reinfarction, stroke, and death following acute coronary occlusion, heparin has not clearly been shown to have additional benefit when added to aspirin but is associated with increased rates of hemorrhagic stroke and major bleeding. At the same time, available data for newer specific thrombin inhibitors such as hirudin suggest greater benefits than aspirin alone or aspirin plus heparin in terms of maintaining coronary flow, but possibly higher risks of hemorrhagic stroke and major bleeding. Since no completed or ongoing large-scale clinical trial has directly compared aspirin plus hirudin, aspirin plus heparin, and aspirin alone, it is not currently possible to decide which of these three antithrombotic regimens provides the optimal bmefit-to-risk ratio. The First American Study of Infarct Survival (ASIS-1) is directly comparing aspirin alone, aspirin plus heparin, and aspirin plus hirudin among 12,000 patients presenting with signs and symptoms of acute myocardial infarction who are not felt by their responsible physicians to be appropriate candidates for thrombolytic therapy. Such patients comprise almost two thirds of all U.S. subjects presenting with acute myocardial infarction and are a group at substantial risk of death, reinfarction, and stroke. Thus, the ASIS-I trial will provide importantly relevant data regarding the optimal antithrombotic regimen for the majority of patients presenting with acute myocardial infarction. In this manuscript we provide the rationale and design for the First American Study of Infarct Survival (ASIS-1), a randomized, double-blind, placebo-controlled trial directly comparing aspirin alone, aspirin plus intravenous heparin, and aspirin plus intravenous hirudin in the treatment of acute myocardial infarction patients not receiving thrombolytic therapy.

Risks for Major Bleeding from Thrombolytic Therapy in Patients with Acute Pulmonary Embolism: Consideration of Noninvasive Management

To assess the relative risks for bleeding with thrombolytic therapy in patients who are managed using pulmonary angiograms compared with those managed using noninvasive tests, primarily the ventilation-perfusion lung scan. A decision analysis based on data from other studies. The risk for major bleeding in patients with pulmonary embolism who receive thrombolytic therapy after a noninvasive diagnosis was assessed from complications of thrombolytic therapy in patients with myocardial infarction, assuming that the same risk ratio for major bleeding when comparing an invasive with a noninvasive approach applied to patients with pulmonary embolism. The risk ratio was 3.3 (95% CI, 1.5 to 9.8) for major bleeding in patients with myocardial infarction. One or more major complications of pulmonary angiography occurred in 1.3% of patients (CI, 0.6% to 1.9%). The average reported risk was 14% (18 of 129 patients) (CI, 7.9% to 20.1%) for major bleeding in patients who had pulmonary angiography before receiving tissue plasminogen activator (tPA). The estimated risk was 4.2% (estimated CI, 1.4% to 9.3%) for major bleeding with tPA after a noninvasive diagnosis of pulmonary embolism. Assuming a risk of 1.3% for major complications from pulmonary angiography, a risk for major hemorrhage of 14.0% for an invasive diagnosis, and a risk of 4.2% for a noninvasive diagnosis, fewer complications would occur with noninvasive management if the prevalence of pulmonary embolism exceeded 21%. Among patients with suspected pulmonary embolism who are candidates for thrombolytic therapy, it is safer to use noninvasive diagnostic tests in many patients.

Characterization of recombinant proteins: biochemical and biophysical criteria for the identity of native and renatured human tissue plasminogen activator and its mutants.

Rapid progress in recombinant DNA techniques has led to the production of a great variety of native and modified proteins in bacteria which, however, frequently occur in non-native conformations or in aggregated form. Renaturation methods must necessarily include criteria for the confirmation of the native structure and function of the refolded macromolecules. This Review describes some of the spectroscopic and thermodynamic techniques which can provide powerful tests for the identity of native and renatured proteins. Emphasis was laid on the concentration requirements of the methods and on the ease of application and availability of instrumentation. As an example we used the single-chain recombinant tissue plasminogen activator (rt-PA) at different pH values and buffer systems. t-PA is a monomeric serine proteinase of M(r) 68,000 that converts plasminogen into plasmin, thereby promoting the degradation of the fibrin network. This enzyme is a promising candidate for thrombolytic therapy of acute myocardial infarction. On the basis of the cDNA sequence the 527 amino acids of t-PA are likely to occur in five distinct structural domains. Specifically we exemplify the application of microcalorimetric studies for the verification of structural identity on rt-PA.

Direct percutaneous transluminal coronary angioplasty for patients with exclusions from thrombolysis

Direct percutaneous transluminal coronary angioplasty (PTCA) is a recognized alternative to intravenous thrombolytic therapy for early acute myocardial infarction (AMI). Fewer than one half of patients with AMI are candidates for thrombolytic therapy. We reviewed the records of 251 patients with the discharge diagnosis of AMI to determine the number of patients ineligible for thrombolysis who might be treatable with reperfusion methods other than intravenous thrombolysis. Forty percent of the patients ( n = 101) were first seen within 6 hours and 51% ( n = 128) were first seen within 12 hours of symptom onset. One third of the patients ( n = 83) had no clear symptom at the time of initial examination. Exclusion criteria for intravenous thrombolysis were present in 187 of 251 patients (75%). Exclusion criteria for thrombolytic therapy included ECG ineligibility ( n = 133), chest pain for more than 6 hours ( n = 67), and age over 75 years ( n = 64), comprising 79% of all exclusions. Of those first seen within 6 hours of symptom onset, 43 of 101 patients (43%) had an ineligible ECG, and 13 of 101 (13%) had age over 75 as exclusion criteria for thrombolysis. Forty-eight of 251 patients (19%) received intravenous thrombolysis. After early coronary angiography, intracoronary thrombolysis, direct PTCA, and emergency coronary artery bypass grafting were used in an additional 30 patients. The use of other forms of reperfusion therapy increased the number of patients treated early to 70 of 251 (28%) ( p = 0.03). The use of a variety of forms of reperfusion therapy substantially increases the number of patients treated early compared with sole use of intravenous thrombolysis. Most patients with AMI still have exclusion criteria for early therapy, and the diagnosis of acute infarction cannot be established; age, comorbid conditions, and uncertainty regarding the benefits of revascularization in many of these patients limit the use of mechanical coronary recanalization.

The Potential Role of Thrombolytic Therapy in Venous Thrombosis

Anticoagulant therapy for lower extremity deep-vein thrombosis (DVT) has been shown to reduce mortality from pulmonary embolism, but subsequent morbidity from the postthrombotic syndrome remains high. Thrombolytic therapy produces higher lysis rates of venous thrombi than heparin alone. Some studies suggest a lower incidence of postthrombotic sequelae after early use of streptokinase. These potential benefits are limited to those patients without contraindications for this therapy. For the past 3 years we have prospectively studied patients with DVT documented by duplex scanning. The records of these patients were reviewed to determine what proportion of this population would have been candidates for thrombolytic therapy. For this analysis, contraindications to the use of thrombolytic agents included: (1) recent surgery (less than 1 month); (2) recent major trauma; (3) active or recent bleeding; (4) brain disease (cerebrovascular accident, brain tumor, arteriovenous malformation); (5) pregnancy; and (6) bleeding diathesis. Also, patients with prior ipsilateral DVT and those with acute symptoms present for 7 or more days were not considered to be candidates for thrombolytic therapy. A contraindication to thrombolytic therapy was present in 194 (93%) of 209 patients with a diagnosis of DVT, including four patients with a relative contraindication. Two or more contraindications were present in 65 cases (31%). Recent surgery was the most frequent factor precluding therapy, being present in 71 patients. A history of DVT in the affected leg was present in 45 patients. Only 15 (7%) of 209 patients with DVT exhibited no contraindications for thrombolytic treatment. Only a small fraction of patients with venous thrombosis will be potential candidates for this therapy.

Accuracy of computer-interpreted electrocardiography in selecting patients for thrombolytic therapy

A prehospital computer-interpreted electrocardiogram (ECG) was obtained in 1,189 patients with chest pain of suspected cardiac origin during an ongoing trial of prehospital thrombolytic therapy in acute myocardial infarction. Electrocardiograms were performed by paramedics 1.5 ± 1.2 h after the onset of symptoms. Of 391 patients with evidence of acute myocardial infarction, 202 (52%) were identified as having ST segment elevation (acute injury) by the computer-interpreted ECG compared with 259 (66%) by an electrocardiographer (p < 0.001). Of 798 patients with chest pain but no infarction, 785 (98%) were appropriately excluded by computer compared with 757 (95%) by an electrocardiographer (p < 0.001). The positive predictive value of the computer and physician-interpreted ECG was, respectively, 94% and 86% and the negative predictive value was 81% find 85%.Prehospital screening of possible candidates for thrombolytic therapy with the aid of a computerized ECG is feasible, highly specific and with further enhancement can speed the care of all patients with acute myocardial infarction.

Noninvasive identification of myocardium at risk in patients with acute myocardial infarction and nondiagnostic electrocardiograms with technetium-99m-Sestamibi.

Patients who have chest pain without electrocardiographic ST elevation are not candidates for thrombolytic therapy in most clinical trials. This study examined the value of technetium-99m-Sestamibi tomographic imaging to assess myocardial perfusion in patients during chest pain without ST elevation. Tc-99m-Sestamibi was injected in 14 patients who had chest pain without ST elevation, who subsequently developed enzymatic evidence of myocardial infarction within 24 hours. Tomographic imaging was performed 1-6 hours after injection. Thirteen of 14 patients showed significant perfusion defects indicative of acute myocardial infarction consistent with absent perfusion (20 +/- 15% of the left ventricle; range, 2-53%); one patient had normal images. Because of the absence of definitive electrocardiographic changes, only five patients received reperfusion therapy within 6 hours of the onset of chest pain. Regional wall motion abnormalities were present in nine of nine patients undergoing contrast ventriculography and correlated with the location of the Tc-99m-Sestamibi perfusion defect. At the time of subsequent coronary angiography, total arterial occlusion was present in 11 of the 14 patients. The infarct-related artery could be identified in 13 of the 14 patients. In six of these 13 patients, the left circumflex was the infarct-related artery. Patients who have chest pain without electrocardiographic ST elevation may have arterial occlusion and significant myocardium at risk. Tc-99m-Sestamibi imaging may be of benefit in identifying these patients early so that they can be considered for acute reperfusion therapy.

Outcomes of direct coronary angioplasty for acute myocardial infarction in candidates and non-candidates for thrombolytic therapy

Coronary angioplasty without prior thrombolytic therapy was performed in 383 patients with acute myocardial infarction (AMI). Patients were divided into 2 groups depending on whether they were candidates or non-candidates for thrombolytic therapy. Patients were not considered thrombolytic candidates if they: (1) presented in cardiogenic shock, (2) were ≥ 75 years of age, (3) had had coronary artery bypass surgery or, (4) had a reperfusion time of > 6 hours. Thrombolytic and nonthrombolytic candidates had similar rates of reperfusion (92 vs 88%), nonfatal reinfarction (6.0 vs 5.9%) and recurrent myocardial ischemia (1.8 vs 0%). Thrombolytic candidates had a lower mortality rate (3.9 vs 24%, p < 0.0001) and a lower incidence of bleeding (4.6 vs 10.9%, p < 0.05). Improvement in left ventricular ejection fraction at follow-up angiography was 4.4% in thrombolytic and 10.5% in nonthrombolytic candidates (p < 0.002). Ejection fraction improved most in patients with anterior wall AMI (7.7% in thrombolytic candidates, 15.1% in nonthrombolytic candidates) and in patients with reperfusion times > 6 hours (14.2%). These outcomes suggest that direct coronary angioplasty is a viable alternative method of reperfusion in patients with AMI who are candidates for thrombolytic therapy. Nonthrombolytic candidates are a high-risk group of patients. Direct coronary angioplasty may be beneficial in certain subgroups, especially for patients in cardiogenic shock and for patients presenting > 6 hours after the onset of chest pain with evidence of ongoing ischemia.

Risk stratification before thrombolytic therapy in patients with acute myocardial infarction

Several studies in the prethrombolytic era on the treatment of acute myocardial infarction identified selected variables from the patient's history, physical examination, chest roentgenogram and electrocardiogram that could be used to estimate mortality in patients with evolving infarction. To extend such assessment to patients receiving thrombolytic therapy, this study evaluated the prognostic utility of several risk factors in the 3,339 patients (2,742 men, 597 women, aged 24 to 78 years) enrolled in Phase II of the Thrombolysis in Myocardial Infarction (TIMI) trial. Before intravenous tissue plasntinogen activator was given, the presence of each of eight risk factors was noted: age ≥ 270 years, female gender, a history of diabetes mellitus or previous myocardial infarction, electrocardiographic evidence of evolving anterior infarction or atrial fibrillation, evidence on physical examination of mild pulmonary congestion or hypotension (systolic pressure < 100 mm Hg) and sinus tachycardia (heart rate > 100 beats/min).Of the 3,339 patients, the 78 with pulmonary edema or cardiogenic shock were exctaded because their risk was known to be high. Of the remaining 3,261, 864 (26%) had no risk factor (low risk); their mortality rate at 6 weeks was only 1.5%. In contrast, 2,397 (74%) had one or more risk factors (not low risk); of these, 5.3% died in 6 weeks (p < 0.001). Among these with one or more risk factors, mortality at 6 weeks was related to the number of risk factors on admission; those with four or more had a mortality rate at 6 weeks of 17.2%.Thus, these eight risk factors can be easily remembered and assessed in patients with myocardial infarction who are candidates for thrombolytic therapy and can be used to estimate short-term mortality.

Surival following thrombolytic therapy

The results of the major mortality studies of thrombolytic drugs in myocardial infarction demonstrate that streptokinase, APSAC and t-PA reduce mortality significantly. Large studies (GISSI-2 comparing Genentech t-PA with streptokinase and ISIS-3 comparing streptokinase, APSAC and Wellcome t-PA) are currently under way to identify which, if any, of the above agents is the most effective. Review of the results of the reported studies has emphasized the importance of treatment being given as soon as practical after the onset of symptoms. It has also revealed that substantial benefit is achievable in patients often not considered to be candidates for thrombolytic therapy, such as those presenting for treatment between 6 and 24 h after symptom onset, and elderly patients. It is emphasized that important benefit may be missed in clinical practice in deciding who should, or should not, receive thrombolytic drug therapy by complying too rigidly to what were investigative clinical study entry criteria.

Therapies to limit infarct size

Rapid diagnosis of an evolving acute myocardial infarction and institution of thrombolytic therapy in appropriate patients can markedly decrease infarct size and thus reduce cardiovascular morbidity and mortality. Streptokinase (Kabikinase, Streptase) and recombinant tissue plasminogen activator (Activase) are both widely used, effective clot-dissolving agents. Patients who are not candidates for thrombolytic therapy can be treated with other methods, such as anticoagulant therapy, which can greatly reduce infarct size. Intravenous heparin, beta blockers, nitroglycerin, and aspirin have all been shown to limit infarct size, decrease mortality, or do both in patients with acute myocardial infarction.

A community survey of the potential use of thrombolytic agents for acute myocardial infarction.

We surveyed all patients admitted to nine community hospital coronary care units to determine what proportion could be candidates for thrombolytic therapy. During the 12-month study period, there were 4,115 admissions for possible acute myocardial infarction, and 1,076 (26%) had a discharge diagnosis of myocardial infarction. Patients with myocardial infarction had the following characteristics: 60% had ST elevation seen on the first ECG, 17% had ST depression without ST elevation, 75% were less than 75 years old, 75% had no contraindications to thrombolytic therapy, 78% arrived at hospital within six hours of onset of symptoms, and 94% arrived within 24 hours of symptoms. Criteria for administration of thrombolytic therapy can be grouped as restrictive (arrival within six hours of symptoms and ST elevation) or liberal (arrival within 24 hours of symptoms and ST elevation or ST depression). Applying these characteristics, 26% met restrictive criteria for treatment with thrombolytic therapy, and 36% met liberal criteria. Until liberal criteria (therapy up to 24 hours and ST depression) are convincingly shown to be of benefit, we believe clinicians should apply restrictive criteria to potential candidates for thrombolytic therapy.