We performed a meta-analysis of 6 studies we conducted in the United Arab Emirates from 1995 to 2009. These included 1,262 patients with ST-elevation myocardial infarction treated with thrombolytic drugs <6 hours after onset of symptoms and signs of myocardial infarction. All patients were treated with tenecteplase or alteplase to induce coronary thrombolysis. Characteristics of patients in all studies were quite similar. Overall mean age was 47 years, 98% were men, 28% had diabetes, 25% were hypertensive, 20% were hyperlipidemic, 56% were smokers, and 9% had sustained previous myocardial infarction. Incidence of adverse outcomes of 30-day mortality (3%), reinfarction (2.5%), stroke (0.4%), or major bleeding (0%) was low compared to global experience with recanalization regardless of how it was induced. There was no incidence of major bleeding requiring transfusion or laparotomy. In conclusion, in predominantly young men in the United Arab Emirates who were admitted and treated early after onset of an acute ST elevation myocardial infarction, recanalization induced by thrombolysis was an attractive therapeutic approach.
In patients with acute ST-elevation myocardial infarction (STEMI), early recanalization of the infarct-related artery is the lynchpin of treatment. Current guidelines of the American College of Cardiology/American Heart Association and European Society of Cardiology recommend primary percutaneous coronary intervention (PCI) as the preferred option if it implemented promptly by experienced operators. In the United Arab Emirates (UAE), however, our experience has entailed pharmacologically induced thrombolysis for treatment of STEMI virtually exclusively. This report summarizes that experience.
Methods
From 1995 through 2009 we participated in 4 international, multicenter, randomized, controlled, clinical trials and 2 collaborative studies with the University of Vermont, Burlington, in which pharmacologic thrombolysis for treatment of acute STEMI was employed with alteplase (tissue plasminogen activator [t-PA]) or tenecteplase (TNK). The first of the randomized trials was the Continuous Infusion Versus Double Bolus Alteplase (COBALT) study. The other 3 were the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT I, II, III) studies. The 2 studies with the University of Vermont were Comparison of Rapidity of Coronary Recanalization in Men with Tenecteplase Versus Alteplase in Acute Myocardial Infarction (CORRETA) and Erythropoietin to Augment Myocardial Salvage Induced by Coronary Thrombolysis in Patients with ST Segment Elevation Acute Myocardial Infarction (EPO). The 4 international randomized studies were audited by external auditors. ASSENT II was audited also by the Food and Drug Administration.
In the COBALT study, front-loaded infusion of t-PA and double-bolus administration of t-PA yielded equivalent results with a slightly increased incidence of hemorrhage seen with the double bolus. In ASSENT I a single bolus of TNK (30 to 50 mg) yielded results similar to those with front-loaded t-PA seen in other large trials. In ASSENT II TNK and t-PA yielded equivalent results with respect to 30-day mortality. In ASSENT III TNK with enoxaparin or abciximab appeared to be more effective than TNK given with unfractionated heparin in younger patients, a combination that tended to be less effective and possibly unsafe in elderly patients. In the CORRETA study the rapidity of recanalization with TNK or t-PA was evaluated using time activity curves of isoforms of the creatine kinase-MM isoenzyme. TNK induced recanalization more rapidly. In the EPO study erythropoietin soon after onset of STEMI did not increase preservation of jeopardized ischemic myocardium as judged from enzymatically estimated infarct size. We did not measure left ventricular function or ST resolution.
The 1,262 patients in these studies were enrolled within 6 hours (many within 3 hours) after onset of symptoms and signs of acute STEMI and cared for in 3 hospitals in the UAE. Inclusion criteria were chest pain typical of acute MI persisting >30 minutes, ST-segment elevation in ≥2 contiguous limb leads or ≥0.2 mV in 2 such precordial leads or left bundle branch block, and increased concentration of biomarkers. Exclusion criteria were blood pressure >180/110 mm Hg, history of stroke, transient ischemic attack, or dementia, cardiopulmonary resuscitation >10 minutes in duration in the previous 2 weeks, pregnancy or lactation, major surgery, or trauma within 2 months, and inability to adhere to the protocol. In addition, patients were excluded if they had undergone any major head trauma after onset of symptoms of the index MI, current treatment with oral anticoagulation resulting in an international normalized ratio >1.3, participation in any other investigational drug or device study within the previous 30 days, or inability to comply with requirement or follow-up ( Table 1 ). Protocols were approved by institutional review boards at all institutions participating in the study and by regulatory authorities of the UAE.
| Inclusion criteria | |
| 1 | Onset of symptoms indicative of acute myocardial infarction such as chest pain ≥15 minutes in duration within 6 hours |
| 2 | ST elevation ≥0.1 mV in ≥2 contiguous limb leads or ≥0.2 mV in 2 such precordial leads or left bundle-branch block |
| 3 | Age ≥18 years |
| 4 | Negative pregnancy test result in women of childbearing age |
| Exclusion criteria | |
| 1 | Blood pressure >180/110 mm Hg |
| 2 | Hypersensitivity to human protein products |
| 3 | Hemoglobin >15 g/dl or platelet count >350,000/mm 3 |
| 4 | History of stroke, transient ischemic attack, or dementia |
| 5 | Structural central nervous system damage |
| 6 | Cardiopulmonary resuscitation >10 minutes in duration in previous 2 weeks |
| 7 | Pregnancy or lactation (negative pregnancy test result required in women of reproductive age) |
| 8 | Major surgery, visceral organ biopsy, or trauma within 2 months |
| 9 | Inability to adhere to protocol |
After acquisition of written informed consent 1,262 patients (mean age 47.1 years) were studied. Ninety-eight percent were men (in the UAE only 2% of the population are >50 years old and most are men consistent with the large expatriate South Asian workforce), 28% had overt diabetes, 56% were current smokers, 25% had hypertension by history (blood pressure >140/80 mm Hg), and 9% had previous MI. All were admitted within 6 hours after onset of chest pain (mean 3.5 hours; Table 2 ). However, most patients arrived after 1 hour (golden hour). Loci of infarction are listed in Table 3 and medications in Table 4 .
| Studies | Total Patients | Previous MI | Systemic Hypertension | Diabetes Mellitus | Smokers | Men | Women | Age (years), Mean ± SD |
|---|---|---|---|---|---|---|---|---|
| COBALT | 204 | N/A | N/A | N/A | 109 (53%) | 196 (96%) | 8 (4%) | 46.80 ± 8.6 |
| ASSENT I | 154 | 14 (9%) | 32 (21%) | 37 (24%) | 85 (55%) | 149 (97%) | 5 (3%) | 46.4 ± 8.3 |
| ASSENT II | 218 | 31 (14%) | 54 (25%) | 57 (26%) | 129 (59%) | 213 (98%) | 5 (2%) | 47.4 ± 8.8 |
| ASSENT III | 184 | 13 (7%) | 41 (22%) | 54 (29%) | 103 (56%) | 180 (98%) | 4 (2%) | 48.0 ± 8.6 |
| CORRETA | 266 | 19 (7%) | 59 (22%) | 90 (34%) | 146 (55%) | 262 (98%) | 4 (2%) | 46.5 |
| EPO | 236 | 17 (7%) | 77 (33%) | 63 (27%) | 140 (59%) | 234 (99%) | 2 (1%) | 48 |
| Total | 1,262 (100%) | 94 (9%) | 263 (25%) | 301 (28%) | 713 (56%) | 1,234 (98%) | 28 (2%) | 47.1 ± 6 |
| Studies | Anterior | Inferior | Other |
|---|---|---|---|
| COBALT | 120 (59%) | 69 (34%) | 15 (7%) |
| ASSENT I | 77 (50%) | 74 (48%) | 3 (2%) |
| ASSENT II | 113 (52%) | 100 (46%) | 5 (2%) |
| ASSENT III | 103 (56%) | 74 (40%) | 8 (4%) |
| CORRETA | 161 (61%) | 105 (39%) | 0 (0%) |
| EPO | 117 (50%) | 99 (42%) | 20 (8%) |
| Total | 691 (55%) | 521 (41%) | 51 (4%) |
| Studies | Total Patients | Aspirin | β Blockers | ACE Inhibitors | Clopidogrel | Statins | CCBs | ARBs |
|---|---|---|---|---|---|---|---|---|
| COBALT | 204 | 129 (63%) | 153 (75%) | 87 (43%) | 0 (0%) | 8 (4%) | 21 (10%) | 0 (0%) |
| ASSENT I | 154 | 154 (100%) | 125 (81%) | 79 (52%) | 0 (0%) | 12 (8%) | 16 (10%) | 0 (0%) |
| ASSENT II | 218 | 193 (89%) | 161 (74%) | 141 (65%) | 0 (0%) | 107 (49%) | N/A | N/A |
| ASSENT III | 184 | 159 (86%) | 149 (81%) | 120 (65%) | 0 (0%) | 97 (53%) | 9 (5%) | N/A |
| CORRETA | 266 | 266 (100%) | 239 (90%) | 153 (58%) | 0 (0%) | 190 (72%) | 4 (2%) | 11 (4%) |
| EPO | 236 | 236 (100%) | 207 (88%) | 229 (97%) | 236 (100%) | 236 (100%) | 5 (2%) | 4 (2%) |
| Total | 1,262 (100%) | 1,136 (90%) | 1,034 (82%) | 809 (64%) | 236 | 650 (51%) | 54 (4%) | 14 (1%) |
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