Intervention Protocol

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Antibiotics for secondary prevention of coronary heart disease

  1. Maria Skoog1,*,
  2. Berit Grevstad1,
  3. Jørn Wetterslev1,
  4. Asbjørn Hróbjartsson2,
  5. Christian Gluud3

Editorial Group: Cochrane Heart Group

Published Online: 28 FEB 2013

DOI: 10.1002/14651858.CD003610.pub2

How to Cite

Skoog M, Grevstad B, Wetterslev J, Hróbjartsson A, Gluud C. Antibiotics for secondary prevention of coronary heart disease (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD003610. DOI: 10.1002/14651858.CD003610.pub2.

Author Information

  1. 1

    Rigshospitalet, Copenhagen University Hospital, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Copenhagen, Denmark

  2. 2

    Rigshospitalet, The Nordic Cochrane Centre, Copenhagen, Denmark

  3. 3

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, The Cochrane Hepato-Biliary Group, Copenhagen, Denmark

*Maria Skoog, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, DK-2100, Denmark.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 28 FEB 2013



Additional references

Aceti 1996
  • Aceti A, Mazzacurati G, Amendolea M, Pennica A, Zechini B, Trappolini M, et al. Relation of C reactive protein to cardiovascular risk factors. H pylori and C pneumoniae infections may account for most acute coronary syndromes. BMJ 1996;313(7054):428-9.
Agen 1993
  • Agen C, Danesi R, Blandizzi C, Costa M, Stacchini B, Favini P, et al. Macrolide antibiotics as antiinflammatory agents: roxithromycin in an unexpected role. Agents Actions 1993;38(1-2):85-90.
Anderson 1999
  • Anderson JL, Muhlestein JB, Carlquist J, Allen A, Trehan S, Nielson C, et al. Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study. Circulation 1999;99(12):1540-7.
Andraws 2005
  • Andraws R, Berger JS, Brown DL. Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials. JAMA 2005;293(21):2641-7.
Brok 2008
  • Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. Journal of Clinical Epidemiology 2008;61(8):763-9.
Dahlen 1995
  • Dahlen GH, Boman J, Birgander LS, Lindblom B. Lp(a) lipoprotein, IgG, IgA and IgM antibodies to Chlamydia pneumoniae and HLA class II genotype in early coronary artery disease. Atherosclerosis 1995;114(2):165-74.
Danesh 1997
Danesh 1998
Danesh 2000a
Danesh 2000b
Danesh 2002
  • Danesh J, Whincup P, Lewington S, Walker M, Lennon L, Thomson A, et al. Chlamydia pneumoniae IgA titres and coronary heart disease: prospective study and meta-analysis. European Heart Journal 2002;23(5):371-5.
Deeks 1999
  • Deeks JJ, Bradburn MJ, Localio R, Berlin J. Much ado about nothing: meta-analysis for rare events [abstract]. Proceedings of 2nd symposium on systematic reviews: beyond the basics. 1999:23.
DeMets 1987
DerSimonian 1986
Egger 1997
Elbourne 2002
  • Elbourne DR,  Altman DG,  Higgins JP,  Curtin F,  Worthington HV,  Vail A. Meta-analyses involving cross-over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140-9.
Fabricant 1978
Folsom 1998
  • Folsom AR, Nieto FJ, Sorlie P, Chambless LE, Graham DY. Helicobacter pylori seropositivity and coronary heart disease incidence. Atherosclerosis Risk In Communities (ARIC) Study Investigators. Circulation 1998;98(9):845-50.
Gluud 2008
  • Gluud C, Als-Nielsen B, Damgaard M, Fischer Hansen J, Hansen S, Helø OH, et al. CLARICOR Trial Group. Clarithromycin for 2 weeks for stable coronary heart disease: 6-year follow-up of the CLARICOR randomized trial and updated meta-analysis of antibiotics for coronary heart disease. Cardiology 2008;111(4):280-7.
Gupta 1997
  • Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm AJ. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 1997;96(2):404-7.
Gurfinkel 1999
  • Gurfinkel E, Bozovich G, Beck E, Testa E, Livellara B, Mautner B. Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes. The final report of the ROXIS Study. European Heart Journal 1999;20(2):121-7.
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from
ICH-GCP 1997
  • ICH-GCP. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Guideline for good clinical practice. 1997 CFR & ICH Guidelines. 1. Vol. 1, PA 19063-2043, USA: Barnett International/PAREXEL, 1997.
Jadad 1996
  • Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Controlled Clinical Trials 1996;17(1):1-12.
Jespersen 2006
  • Jespersen CM, Als-Nielsen B, Damgaard M, Hansen JF, Hansen S, Helø OH, et al. CLARICOR Trial Group. Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial. BMJ 2006;332(7532):22-7.
Ji 2012
Jüni 2001
Kazar 2005
  • Kazar J,  Kovacova E,  Koncova K,  Cvachova S,  Mongiellova V,  Lietava J,  et al. Chlamydia pneumoniae antibodies and markers of inflammation in patients with cardiovascular diseases. Bratislavské Lekárske Listy 2005;106(11):341-4.
Keus 2010
  • Keus F, Wetterslev J, Gluud C, van Laarhoven CJ. Evidence at a glance: error matrix approach for overviewing available evidence. BMC Medical Research Methodology 2010;10(90):1-14.
Kjaergard 2001
Kuo 1993
Leinonen 1990
  • Leinonen M, Linnanmaki E, Mattila K, Nieminen MS, Valtonen V, Leirisalo-Repo M, et al. Circulating immune complexes containing chlamydial lipopolysaccharide in acute myocardial infarction. Microbial Pathogenesis 1990;9(1):67-73.
Lenzi 2006
  • Lenzi C,  Palazzuoli A,  Giordano N,  Alegente G,  Gonnelli C,  Campagna MS,  et al. H pylori infection and systemic antibodies to CagA and heat shock protein 60 in patients with coronary heart disease. World Journal of Gastroenterology 2006;12(48):7815-20.
Linnanmaki 1993
  • Linnanmaki E, Leinonen M, Mattila K, Nieminen MS, Valtonen V, Saikku P. Chlamydia pneumoniae-specific circulating immune complexes in patients with chronic coronary heart disease. Circulation 1993;87(4):1130-4.
Melnick 1993
  • Melnick SL, Shahar E, Folsom AR, Grayston JT, Sorlie PD, Wang SP, et al. Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis. Atherosclerosis Risk in Communities (ARIC) Study Investigators. American Journal of Medicine 1993;95(5):499-504.
Moher 1998
  • Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?. Lancet 1998;352(9128):609-13.
Moher 2009
  • Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Journal of Clinical Epidemiology 2009 Oct;62(10):1006-12.
Muhlestein 1996
  • Muhlestein JB, Hammond EH, Carlquist JF, Radicke E, Thomson MJ, Karagounis LA, et al. Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic versus other forms of cardiovascular disease. Journal of the American College of Cardiology 1996;27(7):1555-61.
Neumann 2001
  • Neumann F, Kastrati A, Miethke T, Pogatsa-Murray G, Mehilli J, Valina C, et al. Treatment of Chlamydia pneumoniae infection with roxithromycin and effect on neointima proliferation after coronary stent placement (ISAR-3): a randomised, double-blind, placebo-controlled trial. Lancet 2001;357(9274):2085-9.
Patel 1995
  • Patel P, Mendall MA, Carrington D, Strachan DP, Leatham E, Molineaux N, et al. Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. BMJ 1995;311(7007):711-4.
Ramirez 1996
  • Ramirez JA. Isolation of Chlamydia pneumoniae from the coronary artery of a patient with coronary atherosclerosis. The Chlamydia pneumoniae/Atherosclerosis Study Group. Annals of Internal Medicine 1996;125(12):979-82.
Review Manager 2012 [Computer program]
  • The Nordic Cochrane Centre, The Cochane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochane Collaboration, 2012.
Ridker 1999
  • Ridker PM, Kundsin RB, Stampfer MJ, Poulin S, Hennekens CH. Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future myocardial infarction. Circulation 1999;99(9):1161-4.
Roivainen 2000
Romano Carratelli 2006
  • Romano Carratelli C,  Nuzzo I,  Cozzolino D,  Bentivoglio C,  Paolillo R,  Rizzo A. Relationship between Chlamydia pneumoniae infection, inflammatory markers, and coronary heart diseases. International Immunopharmacology 2006;6(5):848-53.
Saikku 1988
  • Saikku P, Leinonen M, Mattila K, Ekman MR, Nieminen MS, Makela PH, et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1988;2(8618):983-6.
Schulz 1995
  • Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408-12.
Shor 1992
  • Shor A, Kuo CC, Patton DL. Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques. South African Medical Journal 1992;82(3):158-61.
Sinisalo 1998
  • Sinisalo J, Mattila K, Nieminen MS, Valtonen V, Syrjala M, Sundberg S, et al. The effect of prolonged doxycycline therapy on Chlamydia pneumoniae serological markers, coronary heart disease risk factors and forearm basal nitric oxide production. The Journal of Antimicrobial Chemotherapy 1998;41(1):85-92.
Thom 1991
  • Thom DH, Wang SP, Grayston JT, Siscovick DS, Stewart DK, Kronmal RA, et al. Chlamydia pneumoniae strain TWAR antibody and angiographically demonstrated coronary artery disease. Arteriosclerosis and Thrombosis 1991;11(3):547-51.
Thom 1992
  • Thom DH, Grayston JT, Siscovick DS, Wang SP, Weiss NS, Daling JR. Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary artery disease. JAMA 1992;268(1):68-72.
Thorlund 2011
  • Thorlund K, Imberger G, Walsh M, Chu R, Gluud C, Wetterslev J, et al. The number of patients and events required to limit the risk of overestimation of intervention effects in meta-analysis - a simulation study. PLoS One 2011;6(10):e25491.
Torgano 1999
  • Torgano G, Cosentini R, Mandelli C, Perondi R, Blasi F, Bertinieri G, et al. Treatment of Helicobacter pylori and Chlamydia pneumoniae infections decreases fibrinogen plasma level in patients with ischemic heart disease. Circulation 1999;99(12):1555-9.
TSA 2011 [Computer program]
  • Copenhagen Trial Unit. Trial Sequential Analysis. Version 0.9. Copenhagen: Copenhagen Trial Unit, 2011.
Wetterslev 2008
  • Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta analysis. Journal of Clinical Epidemiology 2008;61:64-75.
Wetterslev 2009
WHO 2004
  • Mackay J, Mensah G (editors). The Atlas of Heart Disease and Stroke. Geneva: World Health Organization, 2004.
WHO 2011
  • Mendis S, Puska P, Norrving B (editors). Global Atlas on Cardiovascular Disease Prevention and Control. Geneva: World Health Organization, 2011.