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1.  Primary Angioplasty for the Treatment of Acute ST-Segment Elevated Myocardial Infarction 
Executive Summary
One of the longest running debates in cardiology is about the best reperfusion therapy for patients with evolving acute myocardial infarction (MI). Percutaneous transluminal coronary angioplasty (ANGIOPLASTY) is a surgical treatment to reopen a blocked coronary artery to restore blood flow. It is a type of percutaneous (through-the-skin) coronary intervention (PCI) also known as balloon angioplasty. When performed on patients with acute myocardial infarction, it is called primary angioplasty. Primary angioplasty is an alternative to thrombolysis, clot-dissolving drug therapy, for patients with acute MI associated with ST-segment elevation (STEMI), a change recorded with an electrocardiogram (ECG) during chest pain.
This review of the clinical benefits and policy implications of primary angioplasty was requested by the Ontario Health Technology Advisory Committee and prompted by the recent publication of a randomized controlled trial (RCT) in the New England Journal of Medicine (1) that compared referred primary angioplasty with on-site thrombolysis. The Medical Advisory Secretariat reviewed the literature comparing primary angioplasty with thrombolysis and other therapies (pre-hospital thrombolysis and facilitated angioplasty, the latter approach consisting of thrombolysis followed by primary angioplasty irrespective of response to thrombolysis) for acute STEMI.
There have been many RCTs and meta-analyses of these RCTs comparing primary angioplasty with thrombolysis and these were the subject of this analysis. Results showed a statistically significant reduction in mortality, reinfarction, and stroke for patients receiving primary angioplasty. Although the individual trials did not show significant improvements in mortality alone, they did show it for the outcomes of nonfatal reinfarction and stroke, and for an end point combining mortality, reinfarction, and stroke. However, researchers have raised concerns about these studies.
A main concern with the large RCTs is that they lack consistency in methods. Furthermore, there is some question as to their generalizability to practice in Ontario. Across the RCTs, there were differences in the type of thrombolytic drug, the use of stenting versus balloon-only angioplasty, and the use of the newer antiplatelet glycoprotein IIb/IIIa. The largest trial did not offer routine follow-up angioplasty for patients receiving thrombolysis, which is the practice in Ontario, and the meta-analysis included trials with streptokinase, an agent seldom used in hospitals in Ontario. Thus, the true magnitude of mortality benefit can only be surmised from head-to-head comparisons of current standard therapies for primary angioplasty and for thrombolysis.
By taking a more restrictive sample of the available studies, the Medical Advisory Secretariat conducted a review that was more consistent with patterns of practice in Ontario and selected trials that used accelerated alteplase as the thrombolytic agent.
Results from this meta-analysis suggest that the rates for primary angioplasty are significantly better for mortality, reinfarction, and stroke, in the short term (30 days), and for mortality, reinfarction, and the combined end point at 6 months. When primary angioplasty was compared with in-hospital thrombolysis, results showed a significant reduction in adverse event rates associated with primary angioplasty. However, 1 large RCT of pre-hospital thrombolysis (i.e., thrombolysis given by paramedics before arriving at the hospital) compared with primary angioplasty documented that pre-hospital thrombolysis is an equivalent intervention to primary thrombolysis in terms of survival. Furthermore, a meta-analysis of studies that compared pre-hospital thrombolysis with in-hospital thrombolysis showed a reduction in all hospital mortality rates in favour of pre-hospital thrombolysis, supporting the findings of the pre-hospital thrombolysis study. (2)
Clinical trials to date have reported that hospital stay is often reduced for patients who receive primary angioplasty compared with thrombolysis. Using a cost-analysis performed alongside the only study from Ontario, the Medical Advisory Secretariat concluded that there might be savings associated with primary angioplasty. These savings may partly offset the investment the provincial government would have to make to increase access to this technology. These savings should also be shown outside of a clinical trial protocol if the overall efficiencies of primary angioplasty are to be verified.
Based on this health technology policy analysis, the Medical Advisory Secretariat concludes that primary angioplasty has advantages with respect to mortality and combined end points compared with in-hospital thrombolysis (Level 1 evidence). However, pre-hospital thrombolysis improves survival compared with in-hospital thrombolysis (Level 1 evidence) and is equivalent to primary angioplasty (Level 1 evidence).
Results from the literature review raise concerns about the loss of therapeutic advantage due to treatment delays, time lapse from symptom onset to revascularization, time-of-day variations, the hospital volume of procedures, and the ability of hospitals to achieve in practice what RCTs have shown.
Furthermore, questions relevant to applying primary angioplasty widely, involve the diagnosis by paramedics, ambulance diversion protocols, paramedic training, and inter-hospital transfer protocols. These logistical considerations need to be addressed to realise the potential to improve patient outcomes. In its analysis, the Medical Advisory Secretariat concludes that it is unrealistic to reorganise the emergency medical services across Ontario to fully implement a primary angioplasty program.
Finally, it is important to evaluate the potential of this technology in the context of Ontario’s health system. This includes urban and rural considerations, the ability to expand access to primary angioplasty and to minimize symptom-to-assessment time through a diverse strategy including public awareness. Therefore, a measured, evaluative approach to adopting this technology is warranted.
Furthermore, the alternative approach to pre-hospital or early thrombolysis, especially within 120 minutes from onset of symptoms, should be considered when developing the approach to improving outcomes for acute MI. This could include efforts to decrease the symptom-to-thrombolysis time through strategies such as a concerted public education program to expedite presentation to emergency rooms after onset of symptoms, a pre-hospital ECG and thrombolysis checklist in ambulances to reduce door-to-needle time on arrival at emergency rooms, and, especially in remote areas, access to pre-hospital thrombolysis.
The Medical Advisory Secretariat therefore recommends that this analysis of primary angioplasty be viewed in the overall context of all interventions for the management of acute MI and, in particular, of improving access to primary angioplasty and maximising the use of early thrombolysis.
Outcomes for patients with acute MI can be improved if efforts are made to optimise the interval from symptom onset to thrombolysis or angioplasty. This will require concerted efforts, including public awareness through education to reduce the symptom-to-emergency room time, and maximising efficiencies in door-to-intervention times for primary angioplasty and for early thrombolysis.
Primary angioplasty and early thrombolysis cannot be considered in isolation from one another. For example, patients who have persistent STEMI 90 minutes after receiving thrombolysis should be considered for angioplasty (“rescue angioplasty”). Furthermore, for patients with acute MI who are in cardiac shock, primary angioplasty is considered the preferred intervention. The concomitant use of primary angioplasty and thrombolysis (“facilitated angioplasty”) is considered experimental and has no place in routine management of acute MI at this time. In remote parts of the province, consideration should be given to introducing pre-hospital thrombolysis as the preferred intervention through upgrading a select number of paramedics to advanced care status.
PMCID: PMC3387753  PMID: 23074449
2.  Emergency department thrombolysis improves door to needle times 
Emergency Medicine Journal : EMJ  2004;21(6):676-680.
Objective: To identify the effect on door to needle (DTN) time of moving the site of thrombolysis delivery from the coronary care unit (CCU) to the emergency department (ED). To ascertain if moving the site of thrombolysis enables appropriate use of thrombolysis.
Design: Prospective cohort study.
Setting: CCU and ED of a 450 bed Scottish district general hospital without on-site primary angioplasty.
Participants: Primary site for thrombolysis of patients presenting to the hospital with ST elevation MI (STEMI) moved from CCU to ED on 1 April 2000. Study patients who had a confirmed STEMI and/or received thrombolytic therapy before this date were defined as the pre-change group; those who were diagnosed as STEMI and/or received thrombolytic therapy after this date were defined as the post-change group.
Statistical analysis: Mann-Whitney test was used to compare medians and χ2 test for categorical data.
Results: 1349 patients were discharged from CCU with a diagnosis of STEMI or received thrombolysis in the ED or CCU between April 1998 and April 2002. There were 632 patients in the pre-change group and 654 patients in the post-change group. Sixty three patients were excluded. Median DTN time for the pre-change group (321 thrombolysed patients) was 64 minutes and median DTN time for the post-change group (324 thrombolysed patients) was 35 minutes, a median difference of 25 minutes (95% CI for difference 20 to 29 minutes, p<0.0001, Mann-Whitney U test). A total of 37 patients were thrombolysed but did not have a final diagnosis of STEMI.
Conclusion: A significant reduction in DTN times accompanied this change in practice in this hospital.
doi:10.1136/emj.2004.014449
PMCID: PMC1726488  PMID: 15496692
3.  Streptokinase neutralisation titres up to 866 days after intravenous streptokinase for acute myocardial infarction. 
British Heart Journal  1993;70(2):119-121.
OBJECTIVE--To follow the change in streptokinase neutralisation titres in a group of patients after treatment with streptokinase for acute myocardial infarction. DESIGN--Venous blood samples suitable for analysis were obtained up to 866 days after treatment with 1.5 million units of streptokinase in 189 patients. The ability of the patient's plasma to inhibit lysis of a thrombin clot by streptokinase was assessed. SETTING--A coronary care unit in a district general hospital. PATIENTS--A retrospective review of coronary care records and the district health authority computer showed that 329 patients who had received streptokinase were alive. All were invited for venepuncture and 220 (67%) attended. Satisfactory samples were obtained from 189 patients. RESULTS--Raised titres of antibody sufficient to neutralise a standard dose of 1.5 million units of streptokinase were found in 90% of patients. There was a fall in streptokinase neutralisation titre with increasing time after administration of streptokinase (r = -0.35, P < 0.0001) and though there was considerable variation among the group the neutralisation titre was higher than in the general population in all patients, even those who had received streptokinase at least two years previously. CONCLUSION--The ability of streptokinase to lyse a thrombin clot was appreciably inhibited in vitro by the plasma from patients who had received 1.5 million units of streptokinase. High streptokinase neutralisation titres persisted for a long time after the use of streptokinase as thrombolytic treatment for acute myocardial infarction. Readministration of streptokinase may not be efficacious for considerably longer than the one year currently advocated. Until the in vivo effects of streptokinase readministration are known a non-antigenic thrombolytic agent should be used instead.
PMCID: PMC1025269  PMID: 8038019
4.  Thrombolytic Therapy for Acute Coronary Obstruction: Status in 1986 
Texas Heart Institute Journal  1986;13(4):433-445.
The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function, and early mortality was studied in subsets of patients in a randomized trial at The Netherlands Interuniversity Cardiological Institute during a 5-year period. Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared to conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. There were 488 patients eligible for this detailed analysis, of whom 245 were allocated for thrombolytic therapy. Early angiography was performed in 212 of the 245 patients. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size measured from cumulative alpha HBDH release was smaller in patients allocated to thrombolytic therapy (median 760 U/l vs. 1179 U/l in controls, p = 0.0001). LVEF measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% vs. 43% in controls, p = 0.0001). The 12-month mortality was lower in patients allocated to thrombolytic therapy (8% vs. 16% in the control group, p < 0.01). In multivariate regression analysis, infarct size limitation, improvement of LVEF, and a 3-month mortality were predicted by ST, time from onset of symptoms to admission, and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with ST of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function, or mortality were observed in the subset of patients with ST less than 1.2 mV admitted 2 to 4 hours after onset of symptoms.
In the long term, improved survival and enhanced quality of life are most evident after thrombolytic therapy in patients with larger anterior wall infarction, and less pronounced in patients with smaller inferior wall infarction. (Texas Heart Institute Journal 1986; 13:433-445)
Images
PMCID: PMC324674  PMID: 15227352
Thrombolysis; streptokinase therapy; myocardial infarction
5.  Pharmacological and Non-Pharmacological Recanalization Strategies in Acute Ischemic Stroke 
According to the guidelines of the European Stroke Organization (ESO) and the American Stroke Association (ASA), acute stroke patients should be managed at stroke units that include well organized pre- and in-hospital care. In ischemic stroke the restoration of blood flow has to occur within a limited time window that is accomplished by fibrinolytic therapy. Newer generation thrombolytic agents (alteplase, pro-urokinase, reteplase, tenecteplase, desmoteplase) have shorter half-life and are more fibrin-specific. Only alteplase has Food and Drug Administration (FDA) approval for the treatment of acute stroke (1996). The National Institute of Neurological Disorders and Stroke (NINDS) trial proved that alteplase was effective in all subtypes of ischemic strokes within the first 3 h. In the European cooperative acute stroke study III trial, intravenous (IV) alteplase therapy was found to be safe and effective (with some restrictions) if applied within the first 3–4.5 h. In middle cerebral artery (MCA) occlusion additional transcranial Doppler insonication may improve the breakdown of the blood clot. According to the ESO and ASA guidelines, intra-arterial (IA) thrombolysis is an option for recanalization within 6 h of MCA occlusion. Further trials on the IA therapy are needed, as previous studies have involved relatively small number of patients (compared to IV trials) and the optimal IA dose of alteplase has not been determined (20–30 mg is used most commonly in 2 h). Patients undergoing combined (IV + IA) thrombolysis had significantly better outcome than the placebo group or the IV therapy alone in the NINDS trial (Interventional Management of Stroke trials). If thrombolysis fails or it is contraindicated, mechanical devices [e.g., mechanical embolus removal in cerebral ischemia (MERCI)- approved in 2004] might be used to remove the occluding clot. Stenting can also be an option in case of acute internal carotid artery occlusion in the future. An intra-aortic balloon was used to increase the collateral blood flow in the Safety and Efficacy of NeuroFlo™ Technology in Ischemic Stroke trial (results are under evaluation). Currently, there is no approved effective neuroprotective drug.
doi:10.3389/fneur.2011.00032
PMCID: PMC3105226  PMID: 21660098
intravenous thrombolysis; intra-arterial thrombolysis; acute stroke; mechanism of recanalization; thrombectomy; alteplase; stroke unit; therapeutic time window
6.  Does a single bolus thrombolytic reduce door to needle time in a district general hospital? 
Emergency Medicine Journal : EMJ  2004;21(2):162-164.
Objectives: To answer the question "In patients presenting with ST elevation acute myocardial infarction (STEMI) and no contraindication to thrombolysis, does the introduction of Tenecteplase reduce door to needle times?"
Methods: Firstly, an observational study was performed to compare the time taken to prepare standard thrombolytic therapy with Tenecteplase. Secondly, door to needle times were compared before and after the introduction of Tenecteplase. The study was powered to be 80% sure of finding a change of 10% in the number of patients meeting the national service framework standard of a 30 minute door to needle time.
Results: Tenecteplase takes 10.5 minutes less time to prepare than standard treatment (p value <0.001). After the introduction of Tenecteplase the percentage of patients receiving thrombolysis in 30 minutes increased from 58% to 76% (p value <0.01)
Conclusion: Tenecteplase is quicker to prepare than standard therapy, resulting in a significant improvement in performance against the national service framework target.
doi:10.1136/emj.2002.003244
PMCID: PMC1726278  PMID: 14988339
7.  Rescue thrombolysis: alteplase as adjuvant treatment after streptokinase in acute myocardial infarction. 
British Heart Journal  1995;74(4):348-353.
BACKGROUND--In acute myocardial infarction patients who do not reperfuse their infarct arteries shortly after thrombolytic treatment have a high morbidity and mortality. Management of this high risk group remains problematic, especially in centres without access to interventional cardiology. Additional thrombolytic treatment may result in reperfusion and improved left ventricular function. METHODS--Failure of reperfusion was assessed non-invasively as less than 25% reduction of ST elevation in the electrocardiographic lead with maximum ST shift on a pretreatment electrocardiogram. 37 patients with acute myocardial infarction who showed electrocardiographic evidence of failed reperfusion 30 minutes after 1.5 MU streptokinase over 60 minutes were randomly allocated to receive either alteplase (tissue type plasminogen activator (rt-PA) 100 mg over three hours) (19 patients) or placebo (18 patients). 43 patients with electrocardiographic evidence of reperfusion after streptokinase acted as controls. Outcome was assessed from the Selvester Q wave score of a predischarge electrocardiogram and a nuclear gated scan for left ventricular ejection fraction 4-6 weeks after discharge. RESULTS--Among patients in whom ST segment elevation was not reduced after streptokinase, alteplase treatment resulted in a significantly smaller electrocardiographic infarct size (14% (8%) v 20% (9%), P = 0.03) and improved left ventricular ejection fraction (44 (10%) v 34% (16%), P = 0.04) compared with placebo. This benefit was confined to patients who failed fibrinogenolysis after streptokinase (fibrinogen > 1 g/l). In patients in whom ST segment elevation was reduced after streptokinase, infarct size and left ventricular ejection fraction were not significantly different from those in patients treated with additional alteplase. CONCLUSION--Patients without electrocardiographic evidence of reperfusion after streptokinase may benefit from further thrombolysis with alteplase.
PMCID: PMC484036  PMID: 7488444
8.  Time to treatment with thrombolytic therapy: determinants and effect on short-term nonfatal outcomes of acute myocardial infarction 
OBJECTIVES: To characterize the extent of delay in administration of thrombolytic therapy to patients with acute myocardial infarction (AMI) in Canada, to examine patient-specific predictors of such delay and to measure the effect of delay on short-term nonfatal cardiac outcomes. DESIGN: Secondary cohort analysis of data from the first international Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO-I) trial. SETTING: Sixty-three acute care hospitals across Canada. SUBJECTS: All 2898 Canadian patients with an AMI enrolled in GUSTO-I. MAIN OUTCOMES: Time before arrival at a hospital ("symptom-to-door" time) and time from arrival to administration of therapy ("door-to-needle" time) for patients who had an AMI outside of a hospital, in clinically relevant categories; proportions of patients with nonfatal, serious cardiac events, including shock, sustained ventricular tachycardia, ventricular fibrillation and asystole. RESULTS: Of the total number of patients enrolled, records were complete for 2708; 2542 of these patients (93.9%) had an AMI outside of a hospital. These 2542 patients presented a median 81 (interquartile range 50 to 130) minutes after the onset of symptoms, and the median time to treatment in hospital was 85 (interquartile range 61 to 115) minutes. Whereas a greater proportion of Canadian patients than of patients enrolled in GUSTO-I in other countries reached hospital within 2 hours of symptom onset (71.5% v. 61.2%, p < 0.001), a greater proportion of Canadian patients experienced in-hospital treatment delays of more than 1 hour (75.3% v. 57.1%, p < 0.001). In an analysis of all 2708 patients with complete records, both the unadjusted and adjusted odds of nonfatal cardiac events for those treated 4 to 6 hours after symptom onset were significantly higher than for those treated within 2 hours (odds ratio 1.60, 95% confidence interval 1.09 to 2.37). CONCLUSION: After arrival at a hospital, Canadian patients enrolled in GUSTO-I received thrombolytic therapy more slowly than trial enrollees in other countries. Such delays are already known to decrease the rate of short-term survival after AMI. The findings further show that long time to treatment also increases the odds of nonfatal, serious cardiac events. Hospitals and physicians caring for patients with AMI should routinely assess whether and how they can improve door-to-needle times.
PMCID: PMC1232779  PMID: 9054819
9.  Hospital Improvement in Time to Reperfusion in Patients with Acute Myocardial Infarction, 1999-2002 
Background: Rapid reperfusion improves survival for patients with acute ST-segment elevation myocardial infarction (STEMI). We sought to analyze recent trends in door-to-reperfusion time and identify hospital characteristics associated with improved performance.
Methods: In this retrospective observational study from the National Registry of Myocardial Infarction 3 and 4 between 1999 and 2002, we analyzed door-to-needle and door-to-balloon times in patients admitted with STEMI and receiving fibrinolytic therapy (n=68,439 patients in 1,015 hospitals) or percutaneous coronary intervention (n=33,647 patients in 421 hospitals) within 6 hours of hospital arrival.
Results: In 1999, only 46% of the patients in the fibrinolytic therapy cohort were treated within the recommended 30-minute door-to-needle time; only 35% of the patients in the percutaneous coronary intervention cohort were treated within the recommended 90-minute door-to-balloon time. Improvement in these times to reperfusion over the 4-year study period was not statistically significant (door-to-needle: -0.01 min/yr, CI -0.24, +0.23, p > 0.9; door-to-balloon: -0.57 min/yr, CI -1.24, +0.10, p=0.09). Only 33% (337/1,015) of hospitals improved door-to-needle time by more than 1 minute per year, and 26% (110/421) improved door-to-balloon time by more than 3 minutes per year. No hospital characteristic was significantly associated with improvement in door-to-needle time. Only high annual percutaneous coronary intervention volume and location in New England were significantly associated with greater improvement in door-to-balloon time.
Conclusions: Fewer than half of patients with STEMI receive reperfusion in the recommended door-to-needle or door-to-balloon time, and mean time to reperfusion has not decreased significantly in recent years. Relatively few hospitals have shown substantial improvement.
Condensed Abstract
We analyzed door-to-needle and door-to-balloon times in patients admitted with ST-segment elevation myocardial infarction and receiving fibrinolytic therapy (n=68,439 patients in 1,015 hospitals) or percutaneous coronary intervention (n=33,647 patients in 421 hospitals) within 6 hours of hospital arrival in the National Registry of Myocardial Infarction 3 and 4. Despite national initiatives to measure and reduce these times, guideline recommendations were met less than half of the time, with no substantial trend toward improvement. Nevertheless, some individual hospitals experienced substantial improvement while others worsened. Structural features of hospitals did not adequately predict change in performance. Other factors need to be identified and used by hospitals for performance improvement programs.
doi:10.1016/j.jacc.2005.04.071
PMCID: PMC1475926  PMID: 16386663
10.  Changing the site of delivery of thrombolytic treatment for acute myocardial infarction from the coronary care unit to the emergency department greatly reduces door to needle time 
Heart  2000;84(2):157-163.
OBJECTIVE—To quantify the change in door to needle time when delivery of thrombolytic treatment of acute myocardial infarction was changed from the coronary care unit to the emergency department.
DESIGN—A comparative observational study using prospectively collected data.
SETTING—Coronary care unit and emergency department of an Australian teaching hospital.
PARTICIPANTS—89 patients receiving thrombolysis in coronary care unit between June 1994 and January 1996, and 100 patients treated in the emergency department between April 1997 and May 1998.
INTERVENTIONS—From April 1997, by agreement between cardiology and emergency medicine, all patients with acute myocardial infarction receiving thrombolysis were treated by emergency physicians in the emergency department.
MAIN OUTCOME MEASURE—Door to needle time measured from time of arrival at the hospital to start of thrombolysis. Other outcomes included pain to needle time and mortality.
RESULTS—Median door to needle times were less for patients treated in the emergency department than in the coronary care unit (37 minutes, 95% confidence interval (CI) 33 to 44 v 80 minutes, 95% CI 70 to 89, respectively; p < 0.0001). Door to needle time was under 60 minutes in 83% of emergency department patients and 26% of coronary care unit patients (57% difference, 95% CI 45% to 69%; p < 0.0001). Median pain to needle time was less for emergency department patients than for coronary care unit patients (161 minutes, 95% CI 142 to 177 v 195 minutes, 95% CI 180 to 209; p = 0.004); times of less than 90 minutes occurred in 18% of emergency department patients v 1% of coronary care unit patients (17% difference, 95% CI 9% to 25%; p < 0.05). Overall mortality was similar in patients treated in the emergency department and the coronary care unit.
CONCLUSIONS—With a collaborative interdepartmental approach, thrombolytic treatment of acute myocardial infarction was more rapid in the emergency department, without compromising patient safety. This should improve the outcome in patients with infarcts treated with thrombolytic agents.


Keywords: thrombolysis; door to needle time; treatment delay; acute myocardial infarction
doi:10.1136/heart.84.2.157
PMCID: PMC1760916  PMID: 10908251
11.  Thrombolytic treatment and proteinuria. 
British Heart Journal  1995;74(4):354-357.
OBJECTIVES--To determine whether patients with acute myocardial infarction undergoing thrombolysis with streptokinase develop changes in renal function. DESIGN--Prospective assessment of renal function in 60 consecutive patients admitted with acute myocardial infarction. SETTING--Tertiary referral centre and city general hospital. PATIENTS--60 consecutive patients with acute myocardial infarction. Thirty eight were given streptokinase and 17 tissue plasminogen activator (alteplase) and five no thrombolytic agent (non-streptokinase group). MAIN OUTCOME MEASURES--Proteinuria and creatinine clearance on admission (day 1) and on days 3 and 6; serum urea and creatinine concentrations on days 1 and 7; streptokinase IgG on days 1, 2, and 7. RESULTS--Significant proteinuria (> 0.15 g/24 h) was found in 31 (82%) of the 38 patients in the streptokinase group (mean 0.47 g/24 h (95% confidence interval 0.35 to 0.6 g/24 h)) in the 24 hours after admission compared with six (27%) out of 22 in the non-streptokinase group (mean 0.17 g/24 h (0.12 to 0.2 g/24 h); P = 0.008). In the streptokinase group this decreased to the normal range by day 3 (mean 0.15 g/24 h (0.1 to 0.22 g/24 h); P = 0.0001 v baseline). Electrophoresis of urine showed the proteinuria to be glomerular in origin. Creatinine clearance and serum creatinine and urea concentrations were similar in both groups. In the streptokinase group detectable streptokinase IgG titres were found in 28 out of 32 (87%) patients. The median titre on admission was 16 (range 0-110); it fell to 3 (range 0-80; P = 0.001) by day 2 and increased to 61 (range 0-7700; P = 0.0002 v baseline) by day 7. CONCLUSIONS--Streptokinase was associated with significant early onset proteinuria of glomerular origin. This started to resolve by day 3 and resulted in no deterioration in overall renal function. The temporal relation to the initial fall in antibody titre suggests that it could be the result of immune complex deposition in the glomeruli.
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PMCID: PMC484037  PMID: 7488445
12.  The Relationship between Grade of Ischemia, Success of Reperfusion, and Type of Thrombolytic Regimen 
Background
This study was aimed to determine whether the grade of ischemia can predict the success of reperfusion in patients treated with thrombolytic therapy (TT) for ST elevation myocardial infarction (STEMI).
Material/Methods
We enrolled 229 consecutive patients with diagnosis of STEMI and receiving TT. Patients were divided into 2 groups – grade 2 ischemia (GI2) and grade 3 ischemia (GI3) – according to initial electrocardiogram (ECG). As TT, fibrin-specific (tissue plasminogen activator (t-PA)) or non-fibrin-specific (streptokinase (SKZ)) regimens were used. Successful reperfusion was defined as >50% resolution of the maximal ST segment on 90-min ECG. We tried to evaluate whether the grade of ischemia could predict the success of reperfusion and if there were any differences in terms of successful reperfusion between different thrombolytic regimens.
Results
The successful reperfusion rate was significantly higher in GI2 than GI3 (82.4% vs. 64.4% respectively, p=0.002). The success rate was lowest at anterior GI3 (55.8%). Although there was no significant difference between thrombolytic regimens in all groups (p=0.77), t-Pa was superior to SKZ in anterior GI3 (63,6% vs. 30%, p=0.061). In addition, in multivariate analysis, GI and infarct localization were found as independent predictors for successful reperfusion with TT (p=0.006 and p=0.042, respectively).
Conclusions
In the current study, we found that GI2 is an independent predictor for successful reperfusion in STEMI treated with TT. Fibrin specific regime should be preferred in anterior GI3.
doi:10.12659/MSM.892645
PMCID: PMC4362488  PMID: 25746841
Ischemia; Myocardial Reperfusion; Thrombolytic Therapy
13.  Pre-dosing antibody levels and efficacy of thrombolytic drugs containing streptokinase. 
British Heart Journal  1994;72(3):222-225.
OBJECTIVE--To evaluate the influence of pretreatment streptokinase resistance titre and the concentration of IgG antibodies to streptokinase on the efficacy of thrombolytic drugs containing streptokinase in restoring coronary patency in acute myocardial infarction. DESIGN--Comparative observational study. SETTING--City general hospital. PATIENTS--One hundred and twenty four previously unexposed patients presenting within six hours of onset of acute myocardial infarction. INTERVENTIONS--Streptokinase, 1.5 MIU as intravenous infusion over 60 minutes (60 patients), or anistreplase, 30 units as intravenous injection over five minutes (64 patients). MAIN OUTCOME MEASURES--Pretreatment streptokinase resistance titre and concentration of IgG antibodies to streptokinase were measured in 96 and 124 patients respectively and coronary patency assessed angiographically at 90 minutes and 24 hours. RESULTS--Pretreatment streptokinase resistance titre and concentrations of IgG antibodies to streptokinase were low and skewed towards higher values. Those patients with coronary occlusion at 24 hours had a significantly higher median streptokinase resistance titre (100 v 50 streptokinase IU ml-1, P = 0.02). There were trends towards a higher streptokinase resistance titre in those patients with coronary occlusion at 90 minutes (50 v 20 streptokinase IU ml-1, P = 0.06) and higher concentrations of IgG antibodies to streptokinase in those with coronary occlusion at both 90 minutes and 24 hours (1.53 v 0.925, P = 0.03; 1.65 v 1.04 micrograms streptokinase binding ml-1, P = 0.06). Coronary patency rates were similar in the two treatment groups. CONCLUSIONS--In the range measured in previously unexposed patients the streptokinase resistance titre has a small, but significant, negative influence on the efficacy of streptokinase and anistreplase. This effect should be considered if retreatment with streptokinase or anistreplase is proposed.
PMCID: PMC1025505  PMID: 7946770
14.  Significance of initial ST segment changes for thrombolytic treatment in first inferior myocardial infarction. 
Heart  1997;77(6):506-511.
OBJECTIVE: To evaluate the benefit to risk ratio of thrombolytic treatment in patients with small inferior acute myocardial infarction (AMI). Controlled studies relating the benefit from thrombolysis with initial electrocardiographic features are scarce and of limited sample size. DESIGN: Retrospective study of 728 patients with a first inferior AMI of six hours' duration from the Intravenous Streptokinase in Acute Myocardial Infarction (ISAM) study comparing streptokinase with placebo stratified by the initial sum ST segment elevation (sigma ST) of 0.8 mV or less and greater than 0.8 mV, and 636 patients from the International Joint Efficacy Comparison of Thrombolytics (INJECT) trial comparing double blind streptokinase with reteplase stratified by either sigma ST or the presence of precordial ST segment depression. RESULTS: ISAM study patients with an sigma ST of greater than 0.8 mV had a significant mortality benefit from streptokinase throughout six years, while those with an sigma ST of 0.8 mV or less showed a trend to higher mortality at six months (6.3% streptokinase v 5.1% placebo). Despite significantly smaller infarcts and fewer clinical complications in patients with an sigma ST of 0.8 mV or less (ISAM and INJECT) or the absence of precordial ST segment depression (INJECT) thrombolytic treatment was associated with higher early mortality than in those with initially larger ST segment deviations. CONCLUSION: Thrombolytic treatment in patients with inferior AMI presenting with larger ST segment deviations is associated with improved survival throughout six years. The risk to benefit ratio, however, in terms of early mortality in patients who have an sigma ST of 0.8 mV or less and no precordial ST segment depression may be unfavourable.
PMCID: PMC484791  PMID: 9227292
15.  Management of acute coronary syndrome in South Africa: insights from the ACCESS (Acute Coronary Events – a Multinational Survey of Current Management Strategies) registry 
Cardiovascular Journal of Africa  2012;23(7):365-370.
Background
The burden of cardiovascular diseases is predicted to escalate in developing countries. While many studies have reported the descriptive epidemiology, practice patterns and outcomes of patients hospitalised with acute coronary syndromes (ACS), these have largely been confined to the developed nations.
Methods
In this prospective, observational registry, 12 068 adults hospitalised with a diagnosis of ACS were enrolled between January 2007 and January 2008 at 134 sites in 19 countries in Africa, Latin America and the Middle East. Data on patient characteristics, treatment and outcomes were collected.
Results
Of the 642 patients from South Africa in the registry, 615 had a confirmed ACS diagnosis and form the basis of this report; 41% had a discharge diagnosis of ST-segment elevation myocardial infarction (STEMI) and 59% a diagnosis of non-ST-segment elevation acute coronary syndrome (NSTE-ACS), including 32% with non-ST-segment elevation myocardial infarction (NSTEMI) and 27% with unstable angina (UA).
During hospitalisation, most patients received aspirin (94%) and a lipid-lowering medication (91%); 69% received a beta-blocker, and 66% an ACE inhibitor/angiotensin receptor blocker. Thrombolytic therapy was used in only 18% of subjects (36% of STEMI patients and 5.5% of NSTE-ACS patients). Angiography was undertaken in 93% of patients (61.3% on the first day), of whom 53% had a percutaneous coronary intervention (PCI) and 14% were referred for coronary artery bypass surgery. Drug-eluting stents were used in 57.9% of cases. Clopidogrel was prescribed at discharge from hospital in 62.2% of patients.
All-cause death at 12 months was 5.7%, and was higher in patients with STEMI versus non-ST-elevation ACS (6.7 vs 5.0%, p < 0.0001). Clinical factors associated with higher risk of death at 12 months included age ≥ 70 years, presence of diabetes mellitus on admission, and a history of stroke/transient ischaemic attack (TIA).
Conclusions
In this observational study of ACS patients, the use of evidence-based pharmacological therapies for ACS was quite high. Interventional rates were high compared to international standards, and in particular the use of drug-eluting stents, yet the clinical outcomes (mortality, re-admission rates and severe bleeding episodes at one year) were favourable, with low rates compared with other studies.
doi:10.5830/CVJA-2012-017
PMCID: PMC3721828  PMID: 22447241
acute coronary syndrome; myocardial infarction; unstable angina; registry; death
16.  Thrombolytic therapy for myocardial infarction facilitated by mobile coronary care. 
The Ulster Medical Journal  2004;73(2):77-84.
BACKGROUND: The benefit of Thrombolytic Therapy (TT) for acute myocardial infarction is time sensitive. In Northern Ireland widespread availability of mobile coronary care units facilitates delivery of TT to heart attack victims. This region-wide prospective observational study assessed the efficacy of various methods of delivery of TT. METHODS: All 15 acute hospitals providing acute coronary care in Northern Ireland participated and data were collected prospectively over six months on all patients admitted with acute myocardial infarction or who received TT. The information was analysed regarding appropriateness of TT, methods and timeliness of delivery of TT and mortality rates. Performance was measured against National Service Framework standards. FINDINGS: Of 1638 patients with acute myocardial infarction 584 were considered eligible for TT and 494 (85 %) received it, in addition to 18 patients without infarction. Of the 512 thrombolysed patients 282 (55%) were treated in hospital coronary care units, 131 (26%) were treated pre-hospital, 97 (19%) in accident and emergency departments, and two in general medical wards. Overall median call-to-needle time was 87 (7-1110) mins and this was shortest for pre-hospital treatment when 55% of call-to-needle times were < or = 60 mins. For patients treated in hospital median door-to-needle time was 46 (0-1065) mins and this was shortest when TT was administered by accident and emergency staff, when 65% of door-to-needle times were < or = 30 mins. In patients with ST elevation myocardial infarction TT was associated with lower mortality, especially when administered pre-hospital. INTERPRETATION: NSF targets for TT are unlikely to be met in Northern Ireland without increasing pre-hospital delivery of TT and by improving collaboration between coronary care and accident and emergency staff with TT availability in accident and emergency departments.
PMCID: PMC2475470  PMID: 15651765
17.  Coronary care follow-up study: acute care required immediately following thrombolytic therapy. 
We carried out a prospective survey of the outcome of patients with 'suspected myocardial infarction', in order to determine where they should be nursed. The delay between onset, admission, transfer to the CCU, the sequelae and side-effects of thrombolytic therapy were noted and were documented prospectively. Of 217 admissions to CCU with a history of chest pain and suspected acute myocardial infarction during a four-month period (mean age was 62.8 years range 31 to 86 years) 202 fulfilled the criteria for suspected myocardial infarction. Streptokinase was given in 129 and alteplase in one patient. The delay between onset of pain and admission was < 4 h in 73, 4 to 12 h in 30 and > 12 h in 23. Elderly patients were just as likely as younger ones to receive thrombolytic therapy (Chi 2 = 3.6; P = 0.6). An eventual diagnosis of acute myocardial infarction was made in 133 of whom 100 received streptokinase. Dysrhythmia or shock was encountered in one-third of those given streptokinase and a quarter of the remainder. Reactions to streptokinase were recorded in 32 mainly hypotension or bradycardia alone or in combination. Forty-five per cent experienced either cardiac complications or drug reactions or both. During one month there were 57 admissions, 50 of whom arrived by ambulance. The mean delay between call out and arrival in the A&E department was 55 min. We concluded patients who are given thrombolytic therapy need close supervision and they should be nursed in a CCU or its equivalent.
PMCID: PMC1294480  PMID: 8315624
18.  Guidelines for the use of intravenous thrombolytic agents in acute myocardial infarction. Ontario Medical Association Consensus Group on Thrombolytic Therapy. 
A consensus group convened under the auspices of the Ontario Medical Association produced guidelines for the use of intravenous thrombolytic agents in acute myocardial infarction. The guidelines, updated to December 1988, include the following points. 1) Any hospital that routinely accepts the responsibility for looking after patients with acute myocardial infarction could offer thrombolytic therapy if monitoring facilities are available and if the staff are experienced in the treatment of cardiac rhythm disturbances. 2) Before treatment, all patients must be carefully screened for factors predisposing to hemorrhagic complications. 3) A physician should be clearly designated as responsible for the care of the patient receiving an infusion and be available in the event of problems. 4) For the two approved agents the usual dosages are as follows: streptokinase, 1.5 million units given over 1 hour; and tissue-type plasminogen activator (tPA), 100 mg over 3 hours, delivered as 60 mg in the first hour (of which 6 to 7 mg should be given as a bolus in the first 1 to 2 minutes) and then an infusion of 20 mg/h over the next 2 hours. 5) Intravenous thrombolytics should be considered for any patient with presumed acute myocardial infarction, as suggested by prolonged chest pain or other appropriate symptoms and typical electrocardiographic changes. Expeditious treatment is critical, since myocardial necrosis occurs within hours. 6) Emergency angiography is indicated for patients with hemodynamic compromise and no apparent response to streptokinase or tPA and in those with recurrent chest pain suggestive of acute myocardial infarction despite an apparent response to intravenous thrombolysis. Angiography before discharge is recommended for patients with postinfarction angina or evidence from noninvasive testing of significant residual ischemic risk. 7) There is insufficient evidence to choose between streptokinase and tPA on the basis of the two most important outcome measures: patient survival and myocardial preservation. More conclusive evidence comparing tPA, streptokinase and another promising agent, acylated plasminogen-streptokinase activator complex, will be available in 1989-90.
PMCID: PMC1269188  PMID: 2497946
19.  QT Dispersion after Thrombolytic Therapy 
Background:
QT dispersion (QTd) is equal to longer QTc minus shorter QTc measured by 12-lead electrocardiogram (ECG). QTd reflects inhomogeneity in repolarization of ventricular myocardium and because of easy and fast measurement of QTd, it can be used to predict high-risk patients for dysrhythmia after Acute Myocardial Infarction (AMI).
Objectives:
This study aimed to assess the effect of thrombolytic therapy on QTd before and 1 hour and 4 days after beginning of thrombolytic therapy.
Patients and Methods:
The patients with chest pain and ST Elevated Myocardial Infarction (STEMI) that underwent thrombolytic therapy were enrolled into this study. Streptokinase was the thrombolytic agent in all the patients. Standard 12-lead (ECG) was evaluated before beginning of thrombolytic therapy (QTd 1) and 1 hour (QTd2) and 4 days (QTd3) after thrombolytic therapy. First, ECG was magnified × 10 for exact calculation of QT and QTd. After all, the variables were compared using one–way analysis of variance (ANOVA). Besides, P ≤ 0.05 was considered as statistically significant.
Results:
This study was conducted on 160 patients. The results revealed no significant differences among QTd 1, QTd 2, and QTd 3 (P > 0.05). At inferior AMI, however, a significant difference was observed among QTd1, QTd2, and QTd3 (P = 0.031).
Conclusions:
Thrombolytic therapy had no significant effects on QTd. Thus, thrombolytic therapy does not increase the risk of arrhythmia.
PMCID: PMC4302504  PMID: 25614860
QT; Electrocardiography; Thrombolysis; Myocardial Infarction; Streptokinase
20.  Baseline characteristics, management practices, and in-hospital outcomes of patients with acute coronary syndromes: Results of the Saudi project for assessment of coronary events (SPACE) registry 
Objectives
The Saudi Project for Assessment of Coronary Events (SPACE) registry is the first in Saudi Arabia to study the clinical features, management, and in-hospital outcomes of acute coronary syndrome (ACS) patients.
Methods
We conducted a prospective registry study in 17 hospitals in Saudi Arabia between December 2005 and December 2007. ACS patients included those with ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction and unstable angina; both were reported collectively as NSTEACS (non-ST elevation acute coronary syndrome).
Results
5055 patients were enrolled with mean age ± SD of 58 ± 12.9 years; 77.4% men, 82.4% Saudi nationals; 41.5% had STEMI, and 5.1% arrived at the hospital by ambulance. History of diabetes mellitus was present in 58.1%, hypertension in 55.3%, hyperlipidemia in 41.1%, and 32.8% were current smokers; all these were more common in NSTEACS patients, except for smoking (all P < 0.0001). In-hospital medications were: aspirin (97.7%), clopidogrel (83.7%), beta-blockers (81.6%), angiotensin converting enzyme inhibitors/angiotensin receptor blockers (75.1%), and statins (93.3%). Median time from symptom onset to hospital arrival for STEMI patients was 150 min (IQR: 223), 17.5% had primary percutaneous coronary intervention (PCI), 69.1% had thrombolytic therapy, and 14.8% received it at less than 30 min of hospital arrival. In-hospital outcomes included recurrent myocardial infarction (1.5%), recurrent ischemia (12.6%), cardiogenic shock (4.3%), stroke (0.9%), major bleeding (1.3%). In-hospital mortality was 3.0%.
Conclusion
ACS patients in Saudi Arabia present at a younger age, have much higher prevalence of diabetes mellitus, less access to ambulance use, delayed treatment by thrombolytic therapy, and less primary PCI compared with patients in the developed countries. This is the first national ACS registry in our country and it demonstrated knowledge-care gaps that require further improvements.
doi:10.1016/j.jsha.2011.05.004
PMCID: PMC3727434  PMID: 23960654
Acute coronary syndromes; Acute myocardial infarction; Unstable angina; Registry; Saudi Arabia; Middle East
21.  The Norwegian tenecteplase stroke trial (NOR-TEST): randomised controlled trial of tenecteplase vs. alteplase in acute ischaemic stroke 
BMC Neurology  2014;14:106.
Background
Alteplase is the only approved thrombolytic agent for acute ischaemic stroke. The overall benefit from alteplase is substantial, but some evidence indicates that alteplase also has negative effects on the ischaemic brain. Tenecteplase may be more effective and less harmfull than alteplase, but large randomised controlled phase 3 trials are lacking. The Norwegian Tenecteplase Stroke Trial (NOR-TEST) aims to compare efficacy and safety of tenecteplase vs. alteplase.
Methods/Design
NOR-TEST is a multi-centre PROBE (prospective randomised, open-label, blinded endpoint) trial designed to establish superiority of tenecteplase 0.4 mg/kg (single bolus) as compared with alteplase 0.9 mg/kg (10% bolus + 90% infusion/60 minutes) for consecutively admitted patients with acute ischaemic stroke eligible for thrombolytic therapy, i.e. patients a) admitted <4½ hours after symptoms onset; b) admitted <4½ hours after awakening with stroke symptoms c) receiving bridging therapy before embolectomy.
Randomisation tenecteplase:alteplase is 1:1. The primary study endpoint is favourable functional outcome defined as modified Rankin Scale 0–1 at 90 days. Secondary study endpoints are: 1) haemorrhagic transformation (haemorrhagic infarct/haematoma); 2) symptomatic cerebral haemorrhage on CT 24–48 hours; 3) major neurological improvement at 24 hours; 4) recanalisation at 24–36 hours; 5) death.
Discussion
NOR-TEST may establish a novel approach to acute ischaemic stroke treatment. A positive result will lead to a more effective, safer and easier treatment for all acute ischaemic stroke pasients.
NOR-TEST is reviewed and approved by the Regional Committee for Medical and Health Research Ethics (2011/2435), and The Norwegian Medicines Agency (12/01402). NOR-TEST is registered with EudraCT No 2011-005793-33 and in ClinicalTrials.gov (NCT01949948).
doi:10.1186/1471-2377-14-106
PMCID: PMC4029902  PMID: 24886064
Acute ischaemic stroke; Alteplase; Intravenous thrombolysis; Tenecteplase
22.  Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries 
European Heart Journal  2009;31(8):943-957.
Aims
Patient access to reperfusion therapy and the use of primary percutaneous coronary intervention (p-PCI) or thrombolysis (TL) varies considerably between European countries. The aim of this study was to obtain a realistic contemporary picture of how patients with ST elevation myocardial infarction (STEMI) are treated in different European countries.
Methods and results
The chairpersons of the national working groups/societies of interventional cardiology in European countries and selected experts known to be involved in the national registries joined the writing group upon invitation. Data were collected about the country and any existing national STEMI or PCI registries, about STEMI epidemiology, and treatment in each given country and about PCI and p-PCI centres and procedures in each country. Results from the national and/or regional registries in 30 countries were included in this analysis. The annual incidence of hospital admission for any acute myocardial infarction (AMI) varied between 90–312/100 thousand/year, the incidence of STEMI alone ranging from 44 to 142. Primary PCI was the dominant reperfusion strategy in 16 countries and TL in 8 countries. The use of a p-PCI strategy varied between 5 and 92% (of all STEMI patients) and the use of TL between 0 and 55%. Any reperfusion treatment (p-PCI or TL) was used in 37–93% of STEMI patients. Significantly less reperfusion therapy was used in those countries where TL was the dominant strategy. The number of p-PCI procedures per million per year varied among countries between 20 and 970. The mean population served by a single p-PCI centre varied between 0.3 and 7.4 million inhabitants. In those countries offering p-PCI services to the majority of their STEMI patients, this population varied between 0.3 and 1.1 million per centre. In-hospital mortality of all consecutive STEMI patients varied between 4.2 and 13.5%, for patients treated by TL between 3.5 and 14% and for patients treated by p-PCI between 2.7 and 8%. The time reported from symptom onset to the first medical contact (FMC) varied between 60 and 210 min, FMC-needle time for TL between 30 and 110 min, and FMC-balloon time for p-PCI between 60 and 177 min.
Conclusion
Most North, West, and Central European countries used p-PCI for the majority of their STEMI patients. The lack of organized p-PCI networks was associated with fewer patients overall receiving some form of reperfusion therapy.
doi:10.1093/eurheartj/ehp492
PMCID: PMC2854523  PMID: 19933242
Acute myocardial infarction; Reperfusion therapy; Thrombolysis; Primary angioplasty; Europe; Mortality; Incidence
23.  Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction. 
BMJ : British Medical Journal  1996;312(7047):1637-1641.
OBJECTIVES--To determine the proportion of patients presenting with acute myocardial infarction who are eligible for thrombolytic therapy. DESIGN--Cohort follow up study. SETTING--The four coronary care units in Auckland, New Zealand. SUBJECTS--All 3014 patients presenting to the units with suspected myocardial infarction in 1993. MAIN OUTCOME MEASURES--Eligibility for reperfusion with thrombolytic therapy (presentation within 12 hours of the onset of ischaemic chest pain with ST elevation > or = 2 mm in leads V1-V3, ST elevation > or = 1 mm in any other two contiguous leads, or new left bundle branch block); proportions of (a) patients eligible for reperfusion and (b) patients with contraindications to thrombolysis; death (including causes); definite myocardial infarction. RESULTS--948 patients had definite myocardial infarction, 124 probable myocardial infarction, and nine ST elevation but no infarction; 1274 patients had unstable angina and 659 chest pain of other causes. Of patients with definite or probable myocardial infarction, 576 (53.3%) were eligible for reperfusion, 39 had definite contraindications to thrombolysis (risk of bleeding). Hence 49.7% of patients (537/1081) were eligible for thrombolysis and 43.5% (470) received this treatment. Hospital mortality among patients eligible for reperfusion was 11.7% (55/470 cases) among those who received thrombolysis and 17.0% (18/106) among those who did not. CONCLUSIONS--On current criteria about half of patients admitted to coronary care units with definite or probable myocardial infarction are eligible for thrombolytic therapy. Few eligible patients have definite contraindications to thrombolytic therapy. Mortality for all community admissions for myocardial infarction remains high.
PMCID: PMC2351378  PMID: 8664716
24.  Debate: Should the elderly receive thrombolytic therapy or primary angioplasty? 
Thrombolysis and primary angioplasty are both recommended reperfusion strategies for elderly patients presenting with myocardial infarction (MI). Primary angioplasty is most beneficial in high-risk patients. While the elderly have a high absolute risk of dying or developing complications after MI, they also have an increased risk of intracranial haemorrhage if they are given thrombolytic therapy. It could therefore be reasonably argued that primary angioplasty is the reperfusion strategy of choice in the elderly. However, primary angioplasty has not been shown to have a greater relative benefit than thrombolytic therapy in the elderly. Recent data from the Fibrinolytic Therapy Trialists' (FTT) Collaborative Group show that thrombolytic therapy significantly reduces mortality compared with control treatment in patients over 75 years of age presenting within 12 h of symptom onset, with ST-segment elevation or bundle branch block. Future advances in adjunctive therapies may improve myocyte perfusion and hence the outcomes achieved by both invasive and noninvasive reperfusion strategies. Better thrombolytic regimens incorporating adjunctive agents such as bivalirudin may reduce the risk of intracranial haemorrhage. Few hospitals can provide a 24-h primary angioplasty service with door-to-balloon times consistently less than 90 min, and thrombolytic therapy is therefore a far more practical option in most instances.
doi:10.1186/cvm-1-3-150
PMCID: PMC59616  PMID: 11714431
angioplasty; elderly; thrombolysis
25.  ‘Mechanical thrombectomy alone’ as a definite therapy for rescue angioplasty 
BMJ Case Reports  2013;2013:bcr2013009002.
Coronary reperfusion strategies for acute ST segment elevation myocardial infarction (STEMI) include primary percutaneous coronary intervention (PCI), intravenous thrombolytic agents and recently mechanical thrombectomy alone during PCI, the latter reserved for those without significant residual disease post-thrombectomy. We describe the success of ‘mechanical thrombectomy alone’ in two young patients undergoing rescue angioplasty at our institution. Both patients were thrombolysed for inferior STEMI. During rescue PCI, post-thrombus aspiration, mild underlying atherosclerotic burden was detected in both patients, thus possibly obviating the need for further balloon angioplasty or stenting. Cost and compliance with long-term dual antiplatelet therapy (DAPT) was an additional factor to avoid stenting. Both patients received aspirin, clopidogrel, heparin and additional standard therapy for myocardial infarction (MI). Medication compliance was ensured by providing 1 month DAPT at no extra cost. Short-term follow-up at 1 and 3 months, for both patients was uneventful. Two-year, long-term follow-up, available for one patient has been uneventful.
doi:10.1136/bcr-2013-009002
PMCID: PMC3618799  PMID: 23513023

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