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Meta-Analysis
. 2015 Aug 21;2015(8):CD008553.
doi: 10.1002/14651858.CD008553.pub2.

Prophylactic lidocaine for myocardial infarction

Arturo J Martí-Carvajal  1 , Daniel Simancas-Racines, Vidhu Anand, Shrikant Bangdiwala
Affiliations
Meta-Analysis

Prophylactic lidocaine for myocardial infarction

Arturo J Martí-Carvajal et al. Cochrane Database Syst Rev. .

Abstract

Background: Coronary artery disease is a major public health problem affecting both developed and developing countries. Acute coronary syndromes include unstable angina and myocardial infarction with or without ST-segment elevation (electrocardiogram sector is higher than baseline). Ventricular arrhythmia after myocardial infarction is associated with high risk of mortality. The evidence is out of date, and considerable uncertainty remains about the effects of prophylactic use of lidocaine on all-cause mortality, in particular, in patients with suspected myocardial infarction.

Objectives: To determine the clinical effectiveness and safety of prophylactic lidocaine in preventing death among people with myocardial infarction.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 3), MEDLINE Ovid (1946 to 13 April 2015), EMBASE (1947 to 13 April 2015) and Latin American Caribbean Health Sciences Literature (LILACS) (1986 to 13 April 2015). We also searched Web of Science (1970 to 13 April 2013) and handsearched the reference lists of included papers. We applied no language restriction in the search.

Selection criteria: We included randomised controlled trials assessing the effects of prophylactic lidocaine for myocardial infarction. We considered all-cause mortality, cardiac mortality and overall survival at 30 days after myocardial infarction as primary outcomes.

Data collection and analysis: We performed study selection, risk of bias assessment and data extraction in duplicate. We estimated risk ratios (RRs) for dichotomous outcomes and measured statistical heterogeneity using I(2). We used a random-effects model and conducted trial sequential analysis.

Main results: We identified 37 randomised controlled trials involving 11,948 participants. These trials compared lidocaine versus placebo or no intervention, disopyramide, mexiletine, tocainide, propafenone, amiodarone, dimethylammonium chloride, aprindine and pirmenol. Overall, trials were underpowered and had high risk of bias. Ninety-seven per cent of trials (36/37) were conducted without an a priori sample size estimation. Ten trials were sponsored by the pharmaceutical industry. Trials were conducted in 17 countries, and intravenous intervention was the most frequent route of administration.In trials involving participants with proven or non-proven acute myocardial infarction, lidocaine versus placebo or no intervention showed no significant differences regarding all-cause mortality (213/5879 (3.62%) vs 199/5848 (3.40%); RR 1.02, 95% CI 0.82 to 1.27; participants = 11727; studies = 18; I(2) = 15%); low-quality evidence), cardiac mortality (69/4184 (1.65%) vs 62/4093 (1.51%); RR 1.03, 95% CI 0.70 to 1.50; participants = 8277; studies = 12; I(2) = 12%; low-quality evidence) and prophylaxis of ventricular fibrillation (76/5128 (1.48%) vs 103/4987 (2.01%); RR 0.78, 95% CI 0.55 to 1.12; participants = 10115; studies = 16; I(2) = 18%; low-quality evidence). In terms of sinus bradycardia, lidocaine effect is imprecise compared with effects of placebo or no intervention (55/1346 (4.08%) vs 49/1203 (4.07%); RR 1.09, 95% CI 0.66 to 1.80; participants = 2549; studies = 8; I(2) = 21%; very low-quality evidence). In trials involving only participants with proven acute myocardial infarction, lidocaine versus placebo or no intervention showed no significant differences in all-cause mortality (148/2747 (5.39%) vs 135/2506 (5.39%); RR 1.01, 95% CI 0.79 to 1.30; participants = 5253; studies = 16; I(2) = 9%; low-quality evidence). No significant differences were noted between lidocaine and any other antiarrhythmic drug in terms of all-cause mortality and ventricular fibrillation. Data on overall survival 30 days after myocardial infarction were not reported. Lidocaine compared with placebo or no intervention increased risk of asystole (35/3393 (1.03%) vs 14/3443 (0.41%); RR 2.32, 95% CI 1.26 to 4.26; participants = 6826; studies = 4; I(2) = 0%; very low-quality evidence) and dizziness/drowsiness (74/1259 (5.88%) vs 16/1274 (1.26%); RR 3.85, 95% CI 2.29 to 6.47; participants = 2533; studies = 6; I(2) = 0%; low-quality evidence). Overall, safety data were poorly reported and adverse events may have been underestimated. Trial sequential analyses suggest that additional trials may not be needed for reliable conclusions to be drawn regarding these outcomes.

Authors' conclusions: This Cochrane review found evidence of low quality to suggest that prophylactic lidocaine has very little or no effect on mortality or ventricular fibrillation in people with acute myocardial infarction. The safety profile is unclear. This conclusion is based on randomised controlled trials with high risk of bias. However (disregarding the risk of bias), trial sequential analysis suggests that additional trials may not be needed to disprove an intervention effect of 20% relative risk reduction. Smaller risk reductions might require additional higher trials.

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Conflict of interest statement

In 2004, Arturo Martí‐Carvajal was employed by Eli Lilly to run a four‐hour workshop on 'How to critically appraise clinical trials on osteoporosis and how to teach this'. This activity was not related to his work with The Cochrane Collaboration or to any Cochrane review.

In 2007, Arturo Martí‐Carvajal was employed by Merck to run a four‐hour workshop on 'How to critically appraise clinical trials and how to teach this'. This activity was not related to his work with The Cochrane Collaboration or to any Cochrane review.

Vidhu Anand: none known.

Shrikant Bangdiwala: The presentation of the results of the sensitivity analysis of the review may be but are in my view unlikely to be informed by results of a grant from the European Commission on "Evaluation and development of measures to uncover and overcome bias due to non‐publication of clnical trials".

Daniel Simancas‐Racines: none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot on all‐cause mortality in 18 lidocaine vs placebo or no intervention trials Funnel plot of data from the meta‐analysis evaluating the effects of lidocaine compared with placebo for preventing all‐cause mortality in patients with proven or not proven acute myocardial infarction (18 trials). This figure shows low risk of publication bias. Individual circles represent point estimates of the included randomised controlled trials. The pattern of distribution simulates an inverted funnel. Larger trials are closer and upper to the pooled estimate. Effect sizes of smaller trials are lower and are more or less symmetrically distributed around the pooled estimate.
5
5
Trial sequential analysis on all‐cause mortality in 18 lidocaine vs placebo or no intervention trials Trial sequential analysis of lidocaine vs placebo or no intervention on all‐cause mortality in participants with or without proven myocardial infarction based on the diversity‐adjusted required information size (DARIS) of 25,777 participants. This DARIS was calculated on the basis of a proportion of participants with suspected myocardial infarction of 3.40% in the control group; RRR of 20% in the experimental intervention group; alpha (α) of 5%; beta (β) of 20%; and diversity of 22%. The cumulative Z‐curve (blue line) did not cross the conventional alpha 5% boundaries (green lines) at any time. After the 14th trial, the cumulative Z‐curve crosses the trial sequential monitoring boundary for futility. Accordingly, although only 45.5% (11,727/25,777) of the DARIS has been obtained, we can reject an intervention effect of 20% or larger. This implies that no additional trials may be needed to disprove an intervention effect of 20% relative risk reduction if bias can be ignored. Smaller risk reductions may require additional trials with larger sample sizes.
6
6
Funnel plot on all‐cause mortality in participants with proven acute myocardial infarction in 16 lidocaine vs placebo or no intervention trials Funnel plot of data from the meta‐analysis of effects of lidocaine compared with placebo for preventing all‐cause mortality in individuals with proven acute myocardial infarction (16 trials). This figure shows low risk of publication bias. The circles show point estimates of the included randomised controlled trials. The pattern of distribution simulates an inverted funnel. Each half of the funnel plot includes eight trials. Larger trials are closer and upper to the pooled estimate. Effect sizes of the smaller trials are lower and are more or less symmetrically distributed around the pooled estimate. The right half of the funnel plot (near the bottom corner) shows two smaller trials with higher standard error and far of the point estimate.
7
7
Trial sequential analysis on all‐cause mortality among participants with myocardial infarction in 16 lidocaine vs placebo or no intervention trials Trial sequential analysis of lidocaine vs placebo or no intervention on all‐cause mortality in participants with myocardial infarction based on the diversity‐adjusted required information size (DARIS) of 9854 participants. This DARIS was calculated on the basis of a proportion of participants with mortality by myocardial infarction of 5.38% in the control group; post hoc selected RRR of 25% in the experimental intervention group; alpha (α) of 5%; beta (β) of 20%; and diversity of 14%. The cumulative Z‐curve (blue line) did not cross the conventional alpha 5% boundaries (green lines). After the 12th trial, the cumulative Z‐curve crossed the trial sequential monitoring boundary for futility. Accordingly, although only 53.30% (5253/9854) of the DARIS has been obtained, we can reject an intervention effect of 25% or larger. Had we calculated the DARIS on the basis of a more realistic RRR like 20% (as we had planned) or less, the obtained information would represent a smaller part of the DARIS. Accordingly, the boundaries for futility would not have been crossed in such scenarios. Therefore, risk reduction of 20% or less may require additional trials with larger sample sizes.
8
8
Trial sequential analysis on cardiac mortality in 12 lidocaine vs placebo or no intervention trials Trial sequential analysis of lidocaine vs placebo or no intervention on cardiac mortality in participants with or without proven myocardial infarction based on the diversity‐adjusted required information size (DARIS) of 22,745 participants. This DARIS was calculated on the basis of a proportion of participants with cardiac mortality among those with suspected myocardial infarction of 1.51% in the control group; post hoc selected RRR of 30% in the experimental intervention group; alpha (α) of 5%; beta (β) of 20%; and diversity of 14%. The cumulative Z‐curve (blue line) crossed the conventional alpha of 5% (green line) after 3 trials suggested harm. After 10 trials, however, the cumulative Z‐curve (blue line) crossed the trial sequential monitoring boundary for futility. Accordingly, after only 36.4% (8277/22,745) of the DARIS had been obtained, we were able to reject an intervention effect of 30% or larger. Had we calculated the DARIS on the basis of a more realistic RRR like 20% (as originally planned) or less, the obtained evidence would represent a smaller part of the DARIS. Accordingly, boundaries for futility would not have been crossed in such scenarios. Therefore, risk reductions of 20% or less may require additional trials with larger sample sizes.
9
9
Funnel plot of data from the meta‐analysis of effects of lidocaine compared with placebo for preventing ventricular fibrillation in individuals with proven or non‐proven acute myocardial infarction (15 trials). This figure shows low risk of publication bias. Circles show point estimates of the included randomised controlled trials. The pattern of distribution simulates an inverted funnel. Trials are symmetrically distributed in each of the halves. Larger trials are closer and upper to the pooled estimate. Effect sizes of the smaller trials are lower and are more or less symmetrically distributed around the pooled estimate.
10
10
Trial sequential analysis on prevention of ventricular fibrillation in 15 lidocaine vs placebo or no intervention trials Trial sequential analysis of lidocaine vs placebo or no intervention on prevention of ventricular fibrillation in participants with or without proven myocardial infarction based on the diversity‐adjusted required information size (DARIS) of 19,271 individuals. This DARIS was calculated on the basis of a proportion of participants with ventricular fibrillation of 2.01% in the control group; post hoc selected RRR of 30% in the experimental intervention group; alpha (α) of 5%; beta (β) of 20%; and diversity of 24%. The cumulative Z‐curve (blue line) did not cross conventional alpha 5% boundaries (green lines). After the 10th trial, the cumulative Z‐curve crosses the trial sequential monitoring boundary for futility. Accordingly, after only 52.2% (10,066/19,271) of the DARIS had been obtained, we were able to reject an intervention effect of 30% or larger. Had we calculated the DARIS on the basis of a more realistic RRR like 20% (as originally planned) or less, the obtained evidence would represent a smaller portion of the DARIS. Accordingly, the boundaries for futility would not have been crossed in such scenarios. Therefore, risk reductions of 20% or less may require additional trials with larger sample sizes.
1.1
1.1. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 1: All‐cause mortality (participants with proven or non‐proven acute myocardial infarction)
1.2
1.2. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 2: All‐cause mortality (subgroup analysis by acute myocardial infarction‐only participants)
1.3
1.3. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 3: All‐cause mortality in acute myocardial infarction‐only participants (subgroup analysis by administration route for lidocaine)
1.4
1.4. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 4: All‐cause mortality (subgroup analysis according to intravenous administration)
1.5
1.5. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 5: All‐cause mortality (subgroup analysis according to bolus‐lidocaine dose)
1.6
1.6. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 6: All‐cause mortality (subgroup analysis according to number of lidocaine boluses)
1.7
1.7. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 7: All‐cause mortality (subgroup analysis according to intravenous infusion dose)
1.8
1.8. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 8: All‐cause mortality (subgroup analysis by clinical setting)
1.9
1.9. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 9: All‐cause mortality (subgroup analysis according to non‐suspected trials with industry bias compared with suspected trials with industry bias)
1.10
1.10. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 10: All‐cause mortality (sensitivity analysis by attrition bias)
1.11
1.11. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 11: Cardiac mortality
1.12
1.12. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 12: Cardiac mortality (sensitivity analysis according to non‐suspected trials of industry bias versus suspected trials of industry bias)
1.13
1.13. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 13: Ventricular fibrillation
1.14
1.14. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 14: Cardiovascular adverse events
1.15
1.15. Analysis
Comparison 1: Lidocaine vs placebo or no intervention, Outcome 15: Neurological adverse events
2.1
2.1. Analysis
Comparison 2: Lidocaine vs disopyramide, Outcome 1: All‐cause mortality
2.2
2.2. Analysis
Comparison 2: Lidocaine vs disopyramide, Outcome 2: All‐cause mortality (sensitivity analysis by risk of attrition bias)
2.3
2.3. Analysis
Comparison 2: Lidocaine vs disopyramide, Outcome 3: Cardiac mortality
2.4
2.4. Analysis
Comparison 2: Lidocaine vs disopyramide, Outcome 4: Ventricular fibrillation
2.5
2.5. Analysis
Comparison 2: Lidocaine vs disopyramide, Outcome 5: Cardiovascular adverse events
2.6
2.6. Analysis
Comparison 2: Lidocaine vs disopyramide, Outcome 6: Neurological adverse events
3.1
3.1. Analysis
Comparison 3: Lidocaine vs tocainide, Outcome 1: All‐cause mortality
3.2
3.2. Analysis
Comparison 3: Lidocaine vs tocainide, Outcome 2: All‐cause mortality (sensitivity analysis by risk of attrition bias)
3.3
3.3. Analysis
Comparison 3: Lidocaine vs tocainide, Outcome 3: Cardiac mortality
3.4
3.4. Analysis
Comparison 3: Lidocaine vs tocainide, Outcome 4: Adverse events
4.1
4.1. Analysis
Comparison 4: Lidocaine vs mexiletine, Outcome 1: All‐cause mortality
4.2
4.2. Analysis
Comparison 4: Lidocaine vs mexiletine, Outcome 2: Cardiac mortality
4.3
4.3. Analysis
Comparison 4: Lidocaine vs mexiletine, Outcome 3: Ventricular fibrillation
4.4
4.4. Analysis
Comparison 4: Lidocaine vs mexiletine, Outcome 4: Adverse events
5.1
5.1. Analysis
Comparison 5: Lidocaine vs propafenone, Outcome 1: Ventricular fibrillation
5.2
5.2. Analysis
Comparison 5: Lidocaine vs propafenone, Outcome 2: Adverse events
6.1
6.1. Analysis
Comparison 6: Lidocaine vs amiodarone, Outcome 1: Ventricular fibrillation
6.2
6.2. Analysis
Comparison 6: Lidocaine vs amiodarone, Outcome 2: Adverse events
7.1
7.1. Analysis
Comparison 7: Lidocaine vs dimethylammonium, Outcome 1: Adverse events
8.1
8.1. Analysis
Comparison 8: Lidocaine vs aprindine, Outcome 1: Adverse events
9.1
9.1. Analysis
Comparison 9: Lidocaine vs pirmenol, Outcome 1: Adverse event
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Sandler 1976 {published data only}
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Sbarbaro 1979 {published data only}
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Solimene 1983 {published data only}
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Touboul 1988 {published data only}
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Valentine 1974 {published data only}
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    1. Valentine PA, Frew JL, Mashford ML, Sloman JG. Lidocaine in the prevention of sudden death in the pre-hospital phase of acute infarction. A double-blind study. New England Journal of Medicine 1974;19:1327-31. [PMID: ] - PubMed
Wennerblom 1982 {published data only}
    1. Wennerblom B, Holmberg S, Rydén L, Wedel H. Antiarrhythmic efficacy and side-effects of lidocaine given in the prehospital phase of acute myocardial infarction. European Heart Journal 1982;3:516-24. [PMID: ] - PubMed
Wyse 1988 {published data only}
    1. Wyse DG, Kellen J, Rademaker A. Prophylactic versus selective lidocaine for early ventricular arrhythmias of myocardial infarction. Journal of the American College of Cardiology 1988;12:507-13. [PMID: ] - PubMed

References to studies excluded from this review

Antman 1992 {published data only}
    1. Antman EM, Berlin JA. Declining incidence of ventricular fibrillation in myocardial infarction. Implications for the prophylactic use of lidocaine. Circulation 1992;86(3):764-73. [PMID: ] - PubMed
Beloev 1983 {published data only}
    1. Beloev I, Tomov I, Dzhonov A, Orbetsov M, Stankusheva G. Effect of the use of lidocaine on patients with acute myocardial infarct. Vutreshni Bolesti 1983;22(3):88-95. [PMID: ] - PubMed
Bernard 1970 {published data only}
    1. Bernard R, Stacquez A, Denolin H, Bernard R, Stacquez A, Denolin H. [Preventive treatment of arrhythmia in acute phase of myocardial infarct]. [French]. Annales de Cardiologie et d Angeiologie 1970;19(1):62-4. - PubMed
Bernard 1972 {published data only}
    1. Bernard R, Lewinson H, Renta C, Thys JP. Hemodynamic effects of xylocaine and ajmaline in myocardial infarction. Archives des Maladies du Coeur et des Vaisseaux 1972;65(10):1215-8. [PMID: ] - PubMed
Bertini 1993 {published data only}
    1. Bertini G, Giglioli C, Rostagno C, Conti A, Russo L, Taddei T, et al. Early out-of-hospital lidocaine administration decreases the incidence of primary ventricular fibrillation in acute myocardial infarction. The Journal of Emergency Medicine 1993;11:667-72. [PMID: 8157902 ] - PubMed
Bleifeld 1973 {published data only}
    1. Bleifeld W, Merx KW, Heinrich KW, Effert S. Controlled trial of prophylactic treatment with lidocaine in acute myocardial infarction. European Journal of Clinical Pharmacology 1973;6:119-26. [PMID: ] - PubMed
Campbell 1978 {published data only}
    1. Campbell NP, Kelly JG, Adgey AA, McDevitt DG, Pantridge JF, Campbell NP, et al. Observations on intravenous administration of lignocaine in patients with myocardial infarction. British Heart Journal 1978;40(12):1371-5. - PMC - PubMed
Campbell 1980 {published data only}
    1. Campbell RWF. Placebo controlled study of prophylaxis of ventricular arrhythmias in acute myocardial infarction. American Heart Journal 1980;100(6 II):995-9. - PubMed
Campbell 1983 {published data only}
    1. Campbell RWF. Treatment and prophylaxis of ventricular arrhythmias in acute myocardial infarction. American Journal of Cardiology 1983;52:55c-9. - PubMed
Church 1972 {published data only}
    1. Church G, Biern R. Prophylactic lidocaine in acute myocardial infarction. Circulation 1972;46 Suppl 2:139.
De Silva 1981 {published data only}
    1. DeSilva RA, Hennekens CH, Lown B, Casscells W. Lignocaine prophylaxis in acute myocardial infarction: an evaluation of randomised trials. Lancet 1981;2(8251):855-8. [PMID: ] - PubMed
Destuelles 1969 {published data only}
    1. Desruelles J, Gerard A, Waucampt JJ, Goethals S, Decalf A. Value of xylocaine in coronary thrombosis. Archives des Maladies du Coeur et des Vaisseaux 1969;62(2):243-6. [PMID: ] - PubMed
    1. Desruelles J, Waucampt JJ, Goethals S, Decalf A. Value of lignocaine in coronary thrombosis (and especially in rhythm disorders in the initial phase of myocardial infarct). Lille Medical 1969;14(10):1219-21. - PubMed
Diederich 1979 {published data only}
    1. Diederich KW, Fassl H, Djonlagic H, Oltmanns D, Floor-Wieringa A. Lidocaine prophylaxis in the pre-hospital phase of acute myocardial infarction. Deutsche Medizinische Wochenschrift 1979;104(28):1006-8. [PMID: ] - PubMed
Egre 1981 {published data only}
    1. Djiane P, Egre A, Perchicot B, Bory M, Serradimigni A, Bruguerolle B, et al. Use of intramuscular lidocaine in the acute stage of myocardial infarction. Archives des Maladies du Coeur et des Vaisseaux 1981;74(8):931-8. [PMID: ] - PubMed
    1. Egre A, Djiane P, Serradimigni A, Bruguerolle B, Valli M, Bouyard P. Utilization of lidocaine in the acute phase of myocardial infarction [Utilisation de la lidocaine a la phase aigue de l'infarctus du myocarde]. Therapie 1981;36(1):71-9. [PMID: ] - PubMed
Fehmers 1972 {published data only}
    1. Fehmers MC, Dunning AJ, Fehmers MC, Dunning AJ. Intramuscularly and orally administered lidocaine in the treatment of ventricular arrhythmias in acute myocardial infarction. American Journal of Cardiology 1972;29(4):514-9. [PMID: ] - PubMed
    1. Fehmers MC, Daatselaar JJ, Dunning AJ. Intramuscular and oral administration of lidocaine for the treatment of ventricular arrhythmias in myocardial infarct. Nederlands Tijdschrift voor Geneeskunde 1972;116(29):1214-20. - PubMed
Formichev 1995 {published data only}
    1. Fomichev VI, Preobrazhenskiï DV. Prophylactic use of lidocaine in the acute period of myocardial infarction. Klinicheskaia Meditsina 1995;73:17-20. [PMID: 7474809] - PubMed
Garratt 1998 {published data only}
    1. Garratt KN, Holmes DR Jr, Molina-Viamonte V, Reeder GS, Hodge DO, Bailey KR, et al. Intravenous adenosine and lidocaine in patients with acute myocardial infarction. American Heart Journal 1998;136(2):196-204. - PubMed
Gianelly 1967 {published data only}
    1. Gianelly R, Groeben JO, Spivack AP, Harrison DC. Effect of lidocaine on ventricular arrhythmias in patients with coronary heart disease. New England Journal of Medicine 1967;277(23):1215-9. [PMID: ] - PubMed
Gonzalez 1977 {published data only}
    1. Gonzalez Carmona V, Cheja Chaya N, Villegas Bermudes J, Gonzalez Carmona V, Cheja Chaya N, Villegas Bermudes J. Use of lidocaine in acute myocardial infarction [Uso de lidocaína en el infarto agudo del miocardio]. Archivos del Instituto de Cardiologia de Mexico 1977;47(5):604-11. - PubMed
Goodman 1979 {published data only}
    1. Goodman SL, Geiderman JM, Bernstein IJ. Prophylactic lidocaine in suspected acute myocardial infarction. JACEP 1979;8(6):221-4. [PMID: ] - PubMed
Hine 1989 {published data only}
    1. Hine LK, Laird N, Hewitt P, Chalmers TC. Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction. Archives of Internal Medicine 1989;149:2694-8. [PMID: ] - PubMed
Iosava 1982 {published data only}
    1. Iosava KV, Areshidze TK, Lezhava MG, Gaprindashvili TG. Effectiveness of lidocaine use in the initial period of acute myocardial infarct. Kardiologiia 1982;22(12):82-5. [PMID: ] - PubMed
Jaffe 1992 {published data only}
    1. Jaffe AS. Prophylactic lidocaine for suspected acute myocardial infarction? Heart Disease and Stroke 1992;1(4):179-83. [PMID: ] - PubMed
Kudenchuk 2013 {published data only}
    1. Kudenchuk PJ, Newell C, White L, Fahrenbruch C, Rea T, Eisenberg M. Prophylactic lidocaine for post resuscitation care of patients with out-of-hospital ventricular fibrillation cardiac arrest. Resuscitation 2013;84(11):1512-8. [PMID: ] - PubMed
Lechleitner 1987 {published data only}
    1. Lechleitner P, Dienstl F. Preventive use of lidocaine in the prehospital phase of acute myocardial infarct. Wiener Medizinische Wochenschrift 1987;137(10-11):216-21. [PMID: ] - PubMed
Leone 1991 {published data only}
    1. Leone A, Mori L, Bertanelli F, Fabiano P. Life-threatening arrhythmias after intravenous lidocaine alone or with magnesium in myocardial infarction complicated by ventricular fibrillation. Singapore Medical Journal 1991;32:169-70. [PMID: ] - PubMed
MacMahon 1988 {published data only}
    1. 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;260:1910-6. [PMID: ] - PubMed
Mazur 1982 {published data only}
    1. Mazur NA, Riabokon' OS, Banshchikov GT. Prevention of ventricular fibrillation using lidocaine in the acute period of a myocardial infarct. Biulleten Vsesoiuznogo Kardiologicheskogo Nauchnogo Tsentra Amn SSSR 1982;5(2):59-64. [PMID: ] - PubMed
Miller 1973 {published data only}
    1. Miller RR, Hilliard G, Lies JE, Massumi RA, Zelis R, Mason DT, et al. Hemodynamic effects of procainamide in patients with acute myocardial infarction and comparison with lidocaine. American Journal of Medicine 1973;55(2):161-8. [PMID: ] - PubMed
Mogensen 1971 {published data only}
    1. Mogensen L. Ventricular tachyarrhythmias and lignocaine prophylaxis in acute myocardial infarction. Acta Medica Scandinavica 1971;513:1-80. [PMID: ] - PubMed
Noneman 1978 {published data only}
    1. Noneman JW, Rogers JF. Lidocaine prophylaxis in acute myocardial infarction. Medicine 1978;57(6):501-15. [PMID: ] - PubMed
Oltmanns 1979 {published data only}
    1. Oltmanns D, Lubben C, Pentz R, Siegers CP. Plasma levels of lidocaine after intramuscular injection and subsequent infusion in patients with acute myocardial infarction. International Journal of Clinical Pharmacology, Therapy, and Toxicology 1982;20(12):582-4. [PMID: ] - PubMed
    1. Oltmanns D, Siegers CP. Pharmacokinetics of lidocaine after intramuscular injection in patients with acute myocardial infarction. Zeitschrift fur Kardiologie 1979;68(3):131-6. [PMID: ] - PubMed
Pentecost 1981 {published data only}
    1. Pentecost BL, De Giovanni JV, Lamb P, Cadigan PJ, Evemy KL, Flint EJ, et al. Reappraisal of lignocaine therapy in management of myocardial infarction. British Heart Journal 1981;45(1):42-7. [PMID: ] - PMC - PubMed
Riabokon' 1980 {published data only}
    1. Riabokon' OS, Piotrovskii VK, Smirnova EB, Metelitsa VI, Mazur NA. Comparative clinical study of trimecaine and lidocaine as anti-arrhythmia agents in myocardial infarct. Kardiologiia 1980;20(10):40-2. [PMID: ] - PubMed
Ribner 1979 {published data only}
    1. Ribner HS, Isaacs ES, Frishman WH, Ribner HS, Isaacs ES, Frishman WH. Lidocaine prophylaxis against ventricular fibrillation in acute myocardial infarction. Progress in Cardiovascular Diseases 1979;21(4):287-313. [PMID: 368880 ] - PubMed
Ruano 1989 {published data only}
    1. Ruano Marco M, Lacueva Moya V, Garcia Pardo J, Martin Montes N, Miquel Servet J, Rodriguez P. Lignocaine prophylaxis for reperfusion arrhythmias during treatment with streptokinase in acute myocardial infarction. Lancet 1989;2(8667):872-3. [PMID: ] - PubMed
Ryden 1973 {published data only}
    1. Ryden L, Waldenstrom A, Ehn L, Holmberg S, Husaini M. Comparison between effectiveness of intramuscular and intravenous lignocaine on ventricular arrhythmia complicating acute myocardial infarction. British Heart Journal 1973;35(11):1124-31. [PMID: ] - PMC - PubMed
Shih 1995 {published data only}
    1. Shih RD, Hollander JE, Burstein JL, Nelson LS, Hoffman RS, Quick AM. Clinical safety of lidocaine in patients with cocaine-associated myocardial infarction. Annals of Emergency Medicine 1995;26:702-6. [PMID: ] - PubMed
Singh 1976 {published data only}
    1. Singh JB, Kocot SL. A controlled trial of intramuscular lidocaine in the prevention of premature ventricular contractions associated with acute myocardial infarction. American Heart Journal 1976;91:430-6. [PMID: ] - PubMed
    1. Singh JB, Kocot SL. A controlled trial of intramuscular lidocaine in the prevention of premature ventricular contractions associated with acute myocardial infarction. Circulation 1973;48(4 Suppl):28. - PubMed
    1. Singh JB, Kocot SL. Controlled trial of Intramuscular lidocaine in prevention of premature ventricular contractions associated with acute myocardial-infarction. Circulation 1973;48(4):8-8. - PubMed
Szeplaki 1973 {published data only}
    1. Szeplaki S, Szilagyi A, Boszormenyi E, Barsi B, Mate K, Kulcsar M, et al. Anti-ischemic effect of lidocaine in the acute phase of myocardial infarct without shock. Orvosi Hetilap 1974;115(12):671-5. [PMID: ] - PubMed
    1. Szeplaki S, Szilagyi A, Szeplaki Z, Boszormenyi E, Barsi B, Mate K, et al. Anti-ischemic effect of lidocaine in the acute state of myocardial infarction. Agressologie 1973;14(5):339-45. [PMID: ] - PubMed
Szeplaki 1976 {published data only}
    1. Szeplaki S, Szilaigyi A, Harsanyi A, Szeplaki Z, Mate K, Kulcsar M, et al. Lidocaine prophylaxis in preinfarction angina and in the reactive stage of myocardial infarction. Agressologie 1976;17(4):245-50. [PMID: ] - PubMed
Teo 1993 {published data only}
    1. Teo KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction. An overview of results from randomized controlled trials. JAMA 1993;270:1589-95. [PMID: ] - PubMed
Wojtala 1982 {published data only}
    1. Wojtala M, Stopczyk M, Wojtala M, Stopczyk M. Relationship between lidocaine-induced suppression of premature excitation and reduced possibility of the appearance of ventricular fibrillation in myocardial infarction. Kardiologia Polska 1982;25(7-8):647-53. [PMID: ] - PubMed
Wyman 2004 {published data only}
    1. Wyman MG, Wyman RM, Cannom DS, Criley JM. Prevention of primary ventricular fibrillation in acute myocardial infarction with prophylactic lidocaine. American Journal of Cardiology 2004;94:545-51. [PMID: ] - PubMed

References to studies awaiting assessment

Bolinska 1971 {published data only}
    1. Bolinska H, Kuczborski M, Bolinska H, Kuczborski M. Lignocaine in the treatment of arrhythmia in acute myocardial infarct. Wiadomosci Lekarskie 1971;24(19):1851-4. [PMID: ] - PubMed
Hopperstead 1980 {published data only}
    1. Hopperstead LO, Myers MH. Prophylactic lidocaine in the early management of acute myocardial infarction. The Journal of the Maine Medical Association 1980;71:77-81. [PMID: 7365324 ] - PubMed
Knight 1973 {published data only}
    1. Knight AL. Prophylactic lidocaine in myocardial infarction. Journal of Occupational Medicine 1973;15(7):604. [PMID: ] - PubMed

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