Note from the National Guideline Clearinghouse (NGC): The National Institute for Health and Clinical Excellence (NICE) commissioned an independent academic centre to perform a systematic literature review on the technology considered in this appraisal and prepare an assessment report. The assessment report for this technology appraisal was prepared by the Liverpool Reviews and Implementation Group (See the "Availability of Companion Documents" field.)
Clinical Effectiveness
Search Strategy
The search incorporated a number of strategies. Search terms for electronic databases included were myocardial infarction/heart infarction and thrombolysis combined with specific drug terms (e.g., alteplase [t-PA], reteplase, streptokinase, tenecteplase, anistreplase, and urokinase.
Electronic searches included the following databases:
- MEDLINE (1980-2001)
- EMBASE (1980-2001)
- Science Citation Index/Web of Science (1988-2001)
- Cochrane Trials Register (2001, 4)
- Health Technology Assessment (HTA) (1992-2001)
- Database of Abstracts of Reviews of effectiveness (DARE) (1998-2001)
Specific search strategies and the number of references retrieved for each search is provided in Appendices III, IV and V of the Assessment Report (see the "Availability of Companion Documents" field).
Searching was limited to English language reports.
Reference lists of included studies and pharmaceutical company submissions were searched to identify other relevant studies. In addition, hand searching of American Heart Journal, Circulation, American Journal of Cardiology, British Medical Journal, European Heart Journal, Heart, Emergency Medicine Journal, International Journal of Cardiology, Journal of the American College of Cardiology, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and Stroke was carried out for the period of January 2001 to January 2002 to identify any newly published papers that might not yet have been indexed in electronic databases.
All the references were exported to Endnote reference database, ISI Research Soft, Cal., USA, version 5.
Inclusion and Exclusion Criteria
The identified citations were assessed for inclusion through two stages and disagreements were settled by discussion at each stage. Two reviewers independently scanned all the titles and abstracts and identified the potentially relevant articles to be retrieved. Full text copies of the selected papers were obtained and assessed independently by two reviewers for inclusion. Studies were considered eligible for inclusion if they met the following criteria:
Study Design
Randomised controlled trials (RCTs) that include comparison of included drugs and any or all of the listed outcomes.
Interventions
Comparison of currently available intravenous thrombolytic therapies administered in the early stages of acute myocardial infarction (AMI) in the hospital or pre-hospital setting. Drugs included in the review were: tissue plasminogen activator (t-PA), reteplase, streptokinase, and tenecteplase. Studies that examine the use of anistreplase (not currently available) or urokinase (not currently licensed for use in thrombolysis in the United Kingdom) were also identified and used to inform the background of the review but not included in the analysis.
Participants
Patients with recent on-set AMI without contraindications to thrombolytic therapy. Diagnosis of AMI to be made through clinical assessment or electrocardiogram (ECG).
Outcomes
Data on the following outcome measures were included:
- Mortality
- Patency of coronary arteries
- Left ventricular function
- Stroke
- Reinfarction
- Bleeding
- Allergy
- Anaphylaxis
Cost-Effectiveness
Search Strategy
The following databases were searched for English language papers.
- MEDLINE
- EMBASE
- NHS Economic Evaluation Database (NHSEED)
- Database of Abstracts of Reviews of Effectiveness (DARE)
- Science Citation Index/Web of Science
- Cochrane Trials Register
- Health Technology Assessment (HTA)
Search strategies and results of the searches undertaken are presented in Appendix VI of the Assessment Report (see the "Availability of Companion Documents" field).
Inclusion and Exclusion Criteria
Using explicit, predetermined criteria, two reviewers independently identified studies for inclusion in the cost-effectiveness review process. Decisions were compared.
Where there was disagreement, both reviewers discussed the paper together and a final decision was made. The inclusion and exclusion criteria used in the review are presented below.
Inclusion Criteria for Economic Evaluation Papers
- Active comparator (streptokinase, alteplase, reteplase, or tenecteplase)
- Efficacy data primarily based on published drug versus drug randomised controlled clinical trial evidence
- Explicit synthesis of costs and outcomes in a cost effectiveness ratio
- Full economic evaluation
- Primary paper
Exclusion Criteria for Economic Evaluation Papers
- Non-drug comparator (e.g., placebo or conservative therapy) or aspirin, urokinase, anistreplase
- Source of clinical efficacy data from non-randomised clinical trial or not explicitly stated
- No attempt to synthesise costs and benefits
- Letters, editorials, reviews, commentaries or methodological papers
All the references were exported to Endnote reference database, ISI Research Soft, Cal., USA, version 5.