A Comparison of Results of Meta-analyses of Randomized Control Trials and Recommendations of Clinical Experts: Treatments for Myocardial Infarction | JAMA | JAMA Network
[Skip to Navigation]
Sign In
Article
July 8, 1992

A Comparison of Results of Meta-analyses of Randomized Control Trials and Recommendations of Clinical Experts: Treatments for Myocardial Infarction

Author Affiliations

From the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital (Dr Antman); Center for Cardiovascular Health Services Research, New England Medical Center (Dr Lau); Harvard Medical School (Drs Antman and Mosteller); the Technology Assessment Group, Department of Health Policy and Management, Harvard School of Public Health (Drs Chalmers and Mosteller, and Mr Kupelnick); and the Department of Veterans Affairs Medical Center (Drs Lau and Chalmers), Boston, Mass.

JAMA. 1992;268(2):240-248. doi:10.1001/jama.1992.03490020088036
Abstract

Objective.  —To examine the temporal relationship between accumulating data from randomized control trials of treatments for myocardial infarction and the recommendations of clinical experts writing review articles and textbook chapters.

Data Sources.  —(1) MEDLINE search from 1966 to present; search terms used were myocardial infarction, clinical trials, multicenter studies, double-blind method, meta-analysis, and the text word "random:"; (2) references from pertinent articles and books; and (3) all editions of English-language general medical texts and manuals and review articles on treatment of myocardial infarction.

Study Selection.  —Randomized control trials of therapies for reducing the risk of total mortality in myocardial infarction (acute and secondary prevention). Review articles and textbook chapters dealing with the general clinical management of patients with myocardial infarction.

Data Extraction.  —Two authors read the material and recorded the results; disagreements were resolved by conference.

Data Synthesis.  —We used the technique of cumulative meta-analysis (performing a new meta-analysis when the results of a new clinical trial are published) and compared the results with the recommendations of the experts for various treatments for myocardial infarction. Discrepancies were detected between the meta-analytic patterns of effectiveness in the randomized trials and the recommendations of reviewers. Review articles often failed to mention important advances or exhibited delays in recommending effective preventive measures. In some cases, treatments that have no effect on mortality or are potentially harmful continued to be recommended by several clinical experts.

Conclusions.  —Finding and analyzing all therapeutic trials in a given field has become such a difficult and specialized task that the clinical experts called on to summarize the evidence in a timely fashion need access to better databases and new statistical techniques to assist them in this important task.(JAMA. 1992;268:240-248)

References
1.
Pub L No. 89-239, 89th Cong S 596, approved October 6, 1965.
2.
Agency for Health Care Policy and Research Omnibus Budget Reconciliation Act of 1989, Pub L No. 101-239.
3.
Lau J, Antman E, Jimenez-Silva J, Kupelnick B, Mosteller F, Chalmers TC.  Cumulative meta-analysis of therapeutic trials for myocardial infarction.  N Engl J Med . In press.
4.
Stampfer MJ, Goldhaber SZ, Yusuf S, Peto R, Hennekens C.  Effect of intravenous streptokinase on acute myocardial infarction: pooled results from randomized trials.  N Engl J Med . 1982;307:1180-1182.Crossref
5.
Furberg CD.  Clinical value of intracoronary streptokinase.  Am J Cardiol . 1984;53:626-627.Crossref
6.
Marder VJ, Francis CW.  Thrombolytic therapy for acute transmural myocardial infarction: intracoronary versus intravenous.  Am J Med . 1984;77:921-928.Crossref
7.
Yusuf S, Collins R, Peto R, et al.  Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: overview of results on mortality, reinfarction, and side-effects from 33 randomized controlled trials.  Eur Heart J . 1985;6:556-585.
8.
Patel B, Kloner RA.  Analysis of reported randomized trials of streptokinase therapy for acute myocardial infarction in the 1980s.  Am J Cardiol . 1987;59:501-504.Crossref
9.
Chalmers TC, Levin HR, Sacks HS, Reitman D, Berrier J, Nagalingam R.  Meta-analysis of clinical trials as a scientific discipline, I: control of bias and comparison with large cooperative trials.  Stat Med . 1987;6:733-744.Crossref
10.
Topol EJ.  Acute myocardial infarction: treatment with thrombolytic therapy.  Cardiol Clin . 1989; 7:827-836.
11.
Naylor CD, Jaglal SB.  Impact of intravenous thrombolysis on short-term coronary revascularization rate: a meta-analysis.  JAMA . 1990;264:697-702.Crossref
12.
Held PH, Teo KK, Yusuf S.  Effects of tissue-type plasminogen activator and anisolyated plasminogen streptokinase activator complex on mortality in acute myocardial infarction.  Circulation . 1990;82:1668-1674.Crossref
13.
Honan MB, Harrell FE Jr, Reimer KA, et al.  Cardiac rupture, mortality, and the timing of thrombolytic therapy: a meta-analysis.  J Am Coll Cardiol . 1990;16:359-367.Crossref
14.
Yusuf S, Collins R, Macmahon S, Peto R.  Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomised trials.  Lancet . 1988;1:1088-1092.Crossref
15.
 Long-term and short-term beta-blockade after myocardial infarction.  Lancet . 1982;1:1159-1161.
16.
Yusuf S, Peto R, Lewis J, Collins R, Sleight P.  Beta blockade during and after myocardial infarction: an overview of the randomized trials.  Prog Cardiovasc Dis . 1985;27:335-371.Crossref
17.
Chalmers TC, Berrier J, Sacks HS, Levin H, Reitman D, Nagalingam R.  Meta-analysis of clinical trials as a scientific discipline, II: replicate variability and comparison of studies that agree and disagree.  Stat Med . 1987;6:733-744.Crossref
18.
Yusuf S, Wittes J, Friedman L.  Overview of results of randomized clinical trials in heart disease, I: treatments following myocardial infarction.  JAMA . 1988;260:2088-2093.Crossref
19.
Chalmers TC, Matta RJ, Smith H, Kunzler AM.  Evidence favoring the use of anticoagulants in the hospital phase of acute myocardial infarction.  N Engl J Med . 1977;297:1091-1096.Crossref
20.
ISIS-2 (Second International Study of Infarct Survival) Collaborative Group.  Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2.  Lancet . 1988;2:349-360.
21.
Macmahon S, Yusuf S.  Effects of lidocaine on ventricular fibrillation, asystole, and early death in patients with suspected acute myocardial infarction.  In: Califf KM, Wagner GS, eds.  Acute Coronary Care, 1987 . Boston, Mass: Martinus Nijhoff; 1987:51-60.
22.
Macmahon S, Collins R, Peto R, Koster RW, Yusuf S.  Effects of prophylactic lidocaine in suspected acute myocardial infarction: an overview of results from the randomized, controlled trials.  JAMA . 1988;260:1910-1916.Crossref
23.
Hine K, Laird N, Hewitt P, Chalmers TC.  Metaanalytic evidence against prophylactic use of lidocaine in acute myocardial infarction.  Arch Intern Med . 1989;149:2694-2698.Crossref
24.
Held PH, Yusuf S, Furberg CD.  Calcium channel blockers in acute myocardial infarction and unstable angina: an overview.  BMJ . 1989;299:1187-1192.Crossref
25.
Teo KK, Yusuf S, Collins R, Held PH, Peto R.  Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomised trials.  BMJ . 1991;303:1499-1503.Crossref
26.
Baber NS, Lewis JA.  Confidence in results of beta-blocker postinfarction trials.  BMJ . 1982;284: 1749-1750.Crossref
27.
Lewis JA.  Beta-blockade after myocardial infarction: a statistical view.  Br J Clin Pharmacol . 1982;14:15S-21S.Crossref
28.
Lewis JA, Ellis SH.  A statistical appraisal of postinfarction beta-blocker trials.  Prim Cardiol . 1982;( (suppl 1) ):31-37.
29.
May GS, Eberlein KA, Furberg CD, Passamani ER, DeMets DL.  Secondary prevention after myocardial infarction: a review of long-term trials.  Prog Cardiovasc Dis . 1982;24:331-352.Crossref
30.
Baber NS, Lewis JA.  Beta-adrenoceptor blockade and myocardial infarction: when should treatment start and for how long should it continue?  Circulation . 1983;67:171-177.Crossref
31.
Furberg CD, Bell RL.  Effect of beta-blocker therapy on recurrent nonfatal myocardial infarction.  Circulation . 1983;67:183-185.Crossref
32.
Loeliger EA.  Oral anticoagulation in the secondary prevention of myocardial infarction.  Acta Med Scand . 1981;( (suppl 651) ):305-315.
33.
Leizorovicz A, Boissel JP.  Oral anticoagulant in patients surviving myocardial infarction: a new approach to old data.  Eur J Clin Pharmacol . 1983; 24:333-336.Crossref
34.
Kaplan K.  Prophylactic anticoagulation following acute myocardial infarction.  Arch Intern Med . 1986;146:593-597.Crossref
35.
 Aspirin after myocardial infarction.  Lancet . 1980; 1:1172-1173.
36.
Canner PL.  Aspirin in coronary heart disease: comparison of six clinical trials.  Isr J Med Sci . 1983; 19:413-423.
37.
Canner PL.  An overview of six clinical trials of aspirin in coronary heart disease.  Stat Med . 1987;6: 255-267.Crossref
38.
Antiplatelet Trialists' Collaboration.  Secondary prevention of vascular disease by prolonged antiplatelet treatment.  BMJ . 1988;296:320-331.Crossref
39.
Erkelens DW.  Combination drug therapy with HMG CoA reductase inhibitors and bile acid sequestrants for hypercholesterolemia.  Cardiology . 1990;77( (suppl 4) ):33-38.Crossref
40.
Holme I.  An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence.  Circulation . 1990;82:1916-1924.Crossref
41.
Rossouw JE, Lewis B, Rifkind BM.  The value of lowering cholesterol after myocardial infarction.  N Engl J Med . 1990;323:1112-1119.Crossref
42.
O'Connor CT, Buring JE, Yusuf S, et al.  An overview of randomized trials of rehabilitation with exercise after myocardial infarction.  Circulation . 1989;80:234-244.Crossref
43.
Oldridge NB, Guyatt GH, Fischer NE, Rimm AA.  Cardiac rehabilitation after myocardial infarction: combined experience of randomized clinical trials.  JAMA . 1988;260:945-950.Crossref
44.
Hine LK, Laird NM, Hewitt P, Chalmers TC.  Meta-analysis of empirical long-term antiarrhythmic therapy after myocardial infarction.  JAMA . 1989;262:3037-3040.Crossref
45.
Chalmers TC.  Informed consent, clinical research, and the practice of medicine.  Trans Am Clin Climatol Assoc . 1982;94:204-212.
46.
Gruppo Italiano per lo Studio Della Streptochinasi Nell'infarto Miocardico (GISSI).  Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction.  Lancet . 1986;1:397-402.
47.
Multicenter Diltiazem Postinfarction Trial Research Group.  The effect of diltiazem on mortality and reinfarction after myocardial infarction.  N Engl J Med . 1988;319:385-392.Crossref
48.
Cardiac Arrhythmia Suppression Trial.  Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhthymia suppression after myocardial infarction.  N Engl J Med . 1989;321:406-412.Crossref
49.
Freiman JA, Chalmers TC, Smith Jr HS, Kuebler RR.  The importance of beta, the type II error, and sample size in the design and interpretation of the randomized controlled trial: survey of two sets of negative trials.  In: Bailar JC III, Mosteller F, eds.  Medical Uses of Statistics . 2nd ed. Boston, Mass: New England Journal of Medicine Books; 1992.
50.
Chalmers I, ed.  Oxford Database of Perinatal Trials. Version 1.2, disk issue 6 . Oxford, England: Oxford University; August 1991.
51.
Chalmers I.  Improving the quality and dissemination of reviews of clinical research.  In: Lock S, ed.  The Future of Medical Journals: In Commemoration of 150 Years of the British Medical Journal . London, England: British Medical Journal; 1991: 127-146.
×