Copyright © 1999 by the European Society of Cardiology.
Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes. The final report of the ROXIS study
a Favaloro Foundation, Buenos Aires, Argentina
b Hospital Durand, Buenos Aires, Argentina
c Hospital Aeronautico, Buenos Aires, Argentina
d Hospital Italiano, Buenos Aires, Argentina
accepted July 29, 1998
Abstract
Aims
Mounting evidence suggests infection, specificallyChlamydia pneumoniae,plays a role in atherosclerosis. We tested whether antibiotic treatment with the macrolide roxithromycin improves clinical outcome in patients with acute non-Q-wave coronary syndromes. Preliminary reports revealed a reduction in events in the roxithromycin group at 30 days. We now report the long-term follow-up results.
Methods and Results
Sixty-four per cent of the initial 202 patients with unstable angina who were randomly assigned to receive either roxithromycin or placebo for 30 days completed the active treatment period. At day 30, the primary triple and double end-point rates were 9% and 4% in the placebo group compared to 2% and 0% in the roxithromycin group (unadjustedP=0·032 and 0·058, respectively). The secondary triple and double end-point rates were again higher in the placebo group at day 90 (12·5% and 6·25% vs 4·37% and 0%, unadjustedP=0·065 and 0·029, respectively), and at day 180 (14·6% and 7·29% vs 8·69% and 2·17%, unadjustedP=0·259 and 0·17, respectively). Anti-C. pneumoniaeIgG titres were unchanged in both groups while C-reactive protein levels decreased in both strategies, with a more significant decrease in the roxithromycin arm (P=0·03). Elevated C-reactive protein levels predicted the need for revascularization.
Conclusions
In this pilot trial, roxithromycin appears to extend the clinical benefit of preventing death and re-infarction for at least 6 months after initial treatment.
Key Words: Atherosclerosis • Chlamydia pneumoniae • macrolide • unstable angina • coronary artery disease • roxithromycin
1 Correspondence: Enrique Gurfinkel, MD, PhD, Favaloro Foundation, Avenue Belgrano 1746, (1093) Buenos Aires, Argentina.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  W. L. Baker and K. A. Couch Azithromycin for the secondary prevention of coronary artery disease: A meta-analysis Am. J. Health Syst. Pharm., April 15, 2007; 64(8): 830 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al. Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline. Circulation, June 20, 2006; 113(24): e873 - e923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al. Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline. Stroke, June 1, 2006; 37(6): 1583 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S.V. Elkind, M. L. C. Tondella, D. R. Feikin, B. S. Fields, S. Homma, and M. R. Di Tullio Seropositivity to Chlamydia pneumoniae Is Associated With Risk of First Ischemic Stroke Stroke, March 1, 2006; 37(3): 790 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Ott, N. E. El Mokhtari, M. Musfeldt, S. Hellmig, S. Freitag, A. Rehman, T. Kuhbacher, S. Nikolaus, P. Namsolleck, M. Blaut, et al. Detection of Diverse Bacterial Signatures in Atherosclerotic Lesions of Patients With Coronary Heart Disease Circulation, February 21, 2006; 113(7): 929 - 937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M Jespersen, B. Als-Nielsen, M. Damgaard, J. F. Hansen, S. Hansen, O. H Helo, P. Hildebrandt, J. Hilden, G. B Jensen, J. Kastrup, et al. Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial BMJ, January 7, 2006; 332(7532): 22 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Andraws, J. S. Berger, and D. L. Brown Effects of Antibiotic Therapy on Outcomes of Patients With Coronary Artery Disease: A Meta-analysis of Randomized Controlled Trials JAMA, June 1, 2005; 293(21): 2641 - 2647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Berman, D. Hasdai, E. Raanani, G. P. Georghiou, L. Kapustin, Y. Chepurko, B. A. Vidne, and E. Hochhauser Ex-vivo effect of roxithromycin on human and rat arterial vasoactivity Interactive CardioVascular and Thoracic Surgery, June 1, 2005; 4(3): 232 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Arno, J C Kaski, D A Smith, J P Akiyu, S E Hughes, and C Baboonian Matrix metalloproteinase-9 expression is associated with the presence of Chlamydia pneumoniae in human coronary atherosclerotic plaques Heart, April 1, 2005; 91(4): 521 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. F. Berg, B. Maraha, A. van der Zee, S. K. Gielis, P. J. M. Roholl, G.-J. Scheffer, M. F. Peeters, and J. A. J. W. Kluytmans Effect of Clarithromycin Treatment on Chlamydia pneumoniae in Vascular Tissue of Patients with Coronary Artery Disease: a Randomized, Double-Blind, Placebo-Controlled Trial J. Clin. Microbiol., March 1, 2005; 43(3): 1325 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A Voils, M. E Evans, M. T Lane, R. H Schosser, and R. P Rapp Use of Macrolides and Tetracyclines for Chronic Inflammatory Diseases Ann. Pharmacother., January 1, 2005; 39(1): 86 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Wells, A. G. Mainous III, and L. M. Dickerson Antibiotics for the Secondary Prevention of Ischemic Heart Disease: A Meta-analysis of Randomized Controlled Trials Arch Intern Med, October 25, 2004; 164(19): 2156 - 2161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sander, K. Winbeck, J. Klingelhofer, T. Etgen, and B. Conrad Progression of Early Carotid Atherosclerosis Is Only Temporarily Reduced After Antibiotic Treatment of Chlamydia pneumoniae Seropositivity Circulation, March 2, 2004; 109(8): 1010 - 1015. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Nieto Antibiotics and Coronary Heart Disease JAMA, January 21, 2004; 291(3): 302 - 303. [Full Text] [PDF]
|
|
|
|
|
|
P. J. Lindsberg and A. J. Grau Inflammation and Infections as Risk Factors for Ischemic Stroke Stroke, October 1, 2003; 34(10): 2518 - 2532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. F. Berg, B. Maraha, G.-J. Scheffer, M. F. Peeters, and J. A. J. W. Kluytmans Effect of Clarithromycin on Inflammatory Markers in Patients with Atherosclerosis Clin. Vaccine Immunol., July 1, 2003; 10(4): 525 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Malik JournalScan Heart, June 1, 2003; 89(6): 695 - 695. [Full Text] [PDF]
|
|
|
|
|
|
J. T. Grayston Antibiotic Treatment of Atherosclerotic Cardiovascular Disease Circulation, March 11, 2003; 107(9): 1228 - 1230. [Full Text] [PDF]
|
|
|
|
|
|
R. Zahn, S. Schneider, B. Frilling, K. Seidl, U. Tebbe, M. Weber, M. Gottwik, E. Altmann, F. Seidel, J. Rox, et al. Antibiotic Therapy After Acute Myocardial Infarction: A Prospective Randomized Study Circulation, March 11, 2003; 107(9): 1253 - 1259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V Pislaru, M. Van Ranst, C. Pislaru, Z. Szelid, G. Theilmeier, J.M Ossewaarde, P. Holvoet, S. Janssens, E. Verbeken, and F. J Van de Werf Chlamydia pneumoniae induces neointima formation in coronary arteries of normal pigs Cardiovasc Res, March 1, 2003; 57(3): 834 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Angiolillo, G. Liuzzo, S. Pelliccioni, E. De Candia, R. Landolfi, F. Crea, A. Maseri, and L. M. Biasucci Combined role of the Lewis antigenic system, Chlamydia pneumoniae, and C-reactive protein in unstable angina J. Am. Coll. Cardiol., February 19, 2003; 41(4): 546 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Spence and J. Norris Infection, Inflammation, and Atherosclerosis Stroke, February 1, 2003; 34(2): 333 - 334. [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Forrester Prevention of Plaque Rupture: A New Paradigm of Therapy Ann Intern Med, November 19, 2002; 137(10): 823 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sander, K. Winbeck, J. Klingelhofer, T. Etgen, and B. Conrad Reduced Progression of Early Carotid Atherosclerosis After Antibiotic Treatment and Chlamydia pneumoniae Seropositivity Circulation, November 5, 2002; 106(19): 2428 - 2433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S.V. Elkind, R. Sciacca, B. Boden-Albala, S. Homma, and M. R. Di Tullio Leukocyte Count Is Associated With Aortic Arch Plaque Thickness Stroke, November 1, 2002; 33(11): 2587 - 2592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Delahaye, E. P. McFadden, and G. de Gevigney The scourge of coronary disease in diabetic patients: will antibiotics sweeten the pill? Eur. Heart J., October 2, 2002; 23(20): 1557 - 1559. [Full Text] [PDF]
|
|
|
|
|
|
J.A. Erkens, O.H. Klungel, R.M.C. Herings, R.P. Stolk, J.A. Spoelstra, D.E. Grobbee, and H.G.M. Leufkens Use of fluorquinolones is associated with a reduced risk of coronary heart disease in diabetes mellitus type 2 patients Eur. Heart J., October 2, 2002; 23(20): 1575 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wiesli, W. Czerwenka, A. Meniconi, F. E. Maly, U. Hoffmann, W. Vetter, and G. Schulthess Roxithromycin Treatment Prevents Progression of Peripheral Arterial Occlusive Disease in Chlamydia pneumoniae Seropositive Men: A Randomized, Double-Blind, Placebo-Controlled Trial Circulation, June 4, 2002; 105(22): 2646 - 2652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Stollberger and J. Finsterer Role of Infectious and Immune Factors in Coronary and Cerebrovascular Arteriosclerosis Clin. Vaccine Immunol., March 1, 2002; 9(2): 207 - 215. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Takeshita, Y. Ono, K. Kozuma, M. Suzuki, Y. Kawamura, N. Yokoyama, T. Furukawa, and T. Isshiki Modulation of oxidative burst of neutrophils by doxycycline in patients with acute myocardial infarction J. Antimicrob. Chemother., February 1, 2002; 49(2): 411 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Boman and M. R. Hammerschlag Chlamydia pneumoniae and Atherosclerosis: Critical Assessment of Diagnostic Methods and Relevance to Treatment Studies Clin. Microbiol. Rev., January 1, 2002; 15(1): 1 - 20. [Abstract] [Full Text]
|
|
|
|
|
|
S. C. Johnston, L. M. Messina, W. S. Browner, M. T. Lawton, C. Morris, and D. Dean C-Reactive Protein Levels and Viable Chlamydia pneumoniae in Carotid Artery Atherosclerosis Stroke, December 1, 2001; 32(12): 2748 - 2752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Monaco, F. Crea, G. Niccoli, F. Summaria, D. Cianflone, R. Bordone, G. Bellomo, and A. Maseri Autoantibodies against oxidized low density lipoproteins in patients with stable angina, unstable angina or peripheral vascular disease; pathophysiological implications Eur. Heart J., September 1, 2001; 22(17): 1572 - 1577. [Abstract] [PDF]
|
|
|
|
|
|
T O'malley, C.A Ludlam, R.A Riemermsa, and K.A.A Fox Early increase in levels of soluble inter-cellular adhesion molecule-1 (sICAM-1). Potential risk factor for the acute coronary syndromes Eur. Heart J., July 2, 2001; 22(14): 1226 - 1234. [Abstract] [PDF]
|
|
|
|
|
|
M. S. Elkind, J. Cheng, B. Boden-Albala, M. C. Paik, and R. L. Sacco Elevated White Blood Cell Count and Carotid Plaque Thickness : The Northern Manhattan Stroke Study Stroke, April 1, 2001; 32(4): 842 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sander, K. Winbeck, J. Klingelhofer, T. Etgen, and B. Conrad Enhanced Progression of Early Carotid Atherosclerosis Is Related to Chlamydia pneumoniae (Taiwan Acute Respiratory) Seropositivity Circulation, March 13, 2001; 103(10): 1390 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. VALASSINA, L. MIGLIORINI, A. SANSONI, G. SANI, D. CORSARO, M. G. CUSI, P. E. VALENSIN, and C. CELLESI Search for Chlamydia pneumoniae genes and their expression in atherosclerotic plaques of carotid arteries J. Med. Microbiol., March 1, 2001; 50(3): 228 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gieffers, H. Fullgraf, J. Jahn, M. Klinger, K. Dalhoff, H. A. Katus, W. Solbach, and M. Maass Chlamydia pneumoniae Infection in Circulating Human Monocytes Is Refractory to Antibiotic Treatment Circulation, January 23, 2001; 103(3): 351 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Shah Link Between Infection and Atherosclerosis: Who Are The Culprits: Viruses, Bacteria, Both, or Neither? Circulation, January 2, 2001; 103(1): 5 - 6. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Vehmaan-Kreula, M. Puolakkainen, M. Sarvas, H. G. Welgus, and P. T. Kovanen Chlamydia pneumoniae Proteins Induce Secretion of the 92-kDa Gelatinase by Human Monocyte- Derived Macrophages Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21 (1): e1 - e8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. J. Gibbs, M. Sian, A. W. M. Mitchell, R. M. Greenhalgh, A. H. Davies, and N. Carey Chlamydia pneumoniae Does Not Influence Atherosclerotic Plaque Behavior in Patients With Established Carotid Artery Stenosis Stroke, December 1, 2000; 31(12): 2930 - 2935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. de Boer, A. C. van der Wal, M. A. Houtkamp, J. M. Ossewaarde, P. Teeling, and A. E. Becker Unstable atherosclerotic plaques contain T-cells that respond to Chlamydia pneumoniae Cardiovasc Res, December 1, 2000; 48(3): 402 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Grayston Secondary Prevention Antibiotic Treatment Trials for Coronary Artery Disease Circulation, October 10, 2000; 102(15): 1742 - 1743. [Full Text] [PDF]
|
|
|
|
|
|
J. B. Muhlestein, J. L. Anderson, J. F. Carlquist, K. Salunkhe, B. D. Horne, R. R. Pearson, T. J. Bunch, A. Allen, S. Trehan, and C. Nielson Randomized Secondary Prevention Trial of Azithromycin in Patients With Coronary Artery Disease : Primary Clinical Results of the ACADEMIC Study Circulation, October 10, 2000; 102(15): 1755 - 1760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Tontsch, B. Noll, J. R. Schaefer, M. Herzum, B. Maisch, and B. Goeke Hyperinsulinemia, Lipoprotein (a), and Chlamydia pneumoniae Antibodies--Are They Risk Factors or Serologic Predictors for Progression of Coronary Artery Disease? Angiology, October 1, 2000; 51(10): 831 - 836. [Abstract] [PDF]
|
|
|
|
 |
|
 S A Morre, W Stooker, W K Lagrand, A J C van den Brule, and H W M Niessen Microorganisms in the aetiology of atherosclerosis J. Clin. Pathol., September 1, 2000; 53(9): 647 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Danesh, P. Whincup, M. Walker, L. Lennon, A. Thomson, P. Appleby, Y.-k. Wong, M. Bernardes-Silva, M. Ward, and R. West Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis Commentary: Adjustment for potential confounders may have been taken too far BMJ, July 22, 2000; 321(7255): 208 - 213. [Abstract] [Full Text]
|
|
|
|
 |
|
 I. W. Fong Emerging relations between infectious diseases and coronary artery disease and atherosclerosis Can. Med. Assoc. J., July 1, 2000; 163(1): 49 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. V. Elkind, I-F. Lin, J. T. Grayston, and R. L. Sacco Chlamydia pneumoniae and the Risk of First Ischemic Stroke : The Northern Manhattan Stroke Study Stroke, July 1, 2000; 31(7): 1521 - 1525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cassone Chlamydia pneumoniae and lipoprotein(a): the right combination for atherosclerosis? Eur. Heart J., April 2, 2000; 21(8): 599 - 600. [PDF]
|
|
|
|
|
|
E. Gurfinkel, G. Bozovich, B. Mautner, J. L. Anderson, J. B. Muhlestein, J. Carlquist, A. Allen, S. Trehan, C. Nielson, S. Hall, et al. Chlamydia pneumoniae in Coronary Artery Disease • Response Circulation, March 28, 2000; 101 (12): e118 - e119. [Full Text] [PDF]
|
|
|
|
|
|
E. Gurfinkel, G. Bozovich, and B. Mautner Chlamydia pneumoniae in Coronary Artery Disease Circulation, March 14, 2000; 101 (10): e95 - e95. [Full Text] [PDF]
|
|
|
|
|
|
A. Shor and J. I. Phillips Chlamydia pneumoniae and Atherosclerosis JAMA, December 1, 1999; 282(21): 2071 - 2073. [Full Text] [PDF]
|
|
|
|
|
|
H. Purcell and K.M. Fox Improving outcome in acute coronary syndromes -- as good as it gets? Eur. Heart J., November 1, 1999; 20(21): 1533 - 1537. [PDF]
|
|
|
|
|
|
Y.-k. Wong, K. D. Dawkins, and M. E. Ward Circulating chlamydia pneumoniae DNA as a predictor of coronary artery disease J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1435 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Epstein and J. Zhu Lack of Association of Infectious Agents With Risk of Future Myocardial Infarction and Stroke : Definitive Evidence Disproving the Infection/Coronary Artery Disease Hypothesis? Circulation, September 28, 1999; 100(13): 1366 - 1368. [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Grayston Does Chlamydia pneumoniae Cause Atherosclerosis? Arch Surg, September 1, 1999; 134(9): 930 - 934. [Full Text] [PDF]
|
|
|
|
|
|
J. Sinisalo, K. Mattila, V. Valtonen, O. Anttonen, J. Juvonen, J. Melin, H. Vuorinen-Markkola, M. S. Nieminen, and for the Clarithromycin in Acute Coronary Syndrome Effect of 3 Months of Antimicrobial Treatment With Clarithromycin in Acute Non-Q-Wave Coronary Syndrome Circulation, April 2, 2002; 105(13): 1555 - 1560. [Abstract] [Full Text] [PDF]
|
|