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Therapeutics

In a pilot study, roxithromycin reduced 1 of 10 end points of ischemic cardiac disease

ACP J Club. 1998 Mar-April; 128:35. doi:10.7326/ACPJC-1998-128-2-035


Source Citation

Gurfinkel E, Bozovich G, Daroca A, Beck E, Mautner B, for the ROXIS Study Group. Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study. Lancet 1997. Aug 9;350:404-7.


Abstract

Objective

To evaluate the effectiveness of roxithromycin for reducing severe recurrent angina, acute myocardial infarction (MI), and death caused by cardiac ischemia in patients with unstable angina or non-Q-wave MI.

Design

Randomized, double-blind, placebo-controlled pilot study with follow-up at 31 days.

Setting

8 coronary care units in Argentina.

Patients

202 patients > 21 years of age, with an episode of angina at rest lasting ≥ 10 minutes in the preceding 48 hours; electrocardiographic evidence of ischemic heart disease; elevated cardiac enzyme levels; history of MI, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery; and history of coronary angiography showing ≥ 70% arterial lumen narrowing of a coronary artery. Exclusion criteria were evolving Q-wave MI, left bundle-branch block, hepatic or renal failure, congestive heart failure, or contraindications to macrolide therapy.

Intervention

Patients were allocated to oral roxithromycin, 150 mg (n = 102) twice a day for 30 days, or placebo (n = 100). At admission, all patients received aspirin, 100 to 325 mg/d, intravenous nitroglycerin, and unfractionated heparin for ≥ 72 hours and ≤ 8 days; β-blockers or calcium-channel blockers were used when appropriate.

Main outcome measures

Severe recurrent angina, acute MI, death caused by cardiac ischemia, and combined outcomes (double end point of angina plus MI, and triple end point of angina plus MI plus death).

Main results

The intention-to-treat analysis found no differences between groups for angina (adjusted P = 0.83), MI (adjusted P = 0.73), death (adjusted P = 0.73), the double end point of angina plus MI (adjusted P = 0.12), or the triple end point of angina plus MI plus death (adjusted P = 0.06). Efficacy analysis of 186 patients who completed the minimum treatment period of 72 hours and were followed for 31 days showed that patients receiving roxithromycin had fewer triple end points (angina plus MI plus death) than did patients receiving placebo (1% vs 10%, adjusted P = 0.04), but did not differ for angina (adjusted P = 0.63), MI (adjusted P = 0.9), death (adjusted P = 0.9), or the double end point of angina plus MI (adjusted P = 0.24).

Conclusion

In a pilot study, patients who received roxithromycin after unstable angina or non-Q-wave myocardial infarction benefited in 1 of 10 outcomes for individual and combined cardiac end points.

Sources of funding: Favaloro Foundation. Roxithromycin and placebo tablets supplied by Hoechst Marion Roussel.

For article reprint: Dr. E. Gurfinkel, Favaloro Foundation, Avenue Belgrano 1746, 1093 Buenos Aires, Argentina. FAX 54-1-381-1001.


Commentary

The study by Gurfinkel and colleagues is based on the intriguing hypothesis that infection with Chlamydia pneumoniae may trigger acute coronary events. Rather weak pathologic and epidemiologic evidence (1) suggests that C. pneumoniae may be involved in the promotion of atherosclerotic plaque growth (2), the organism might be a risk factor for future coronary events (3), or both. However, the link between C. pneumoniae and coronary heart disease has yet to be shown.

Gupta and colleagues (4) provided preliminary evidence that antibiotic treatment of C. pneumoniae could alter the clinical course of patients with MI. The trial by Gurfinkel and colleagues adds further preliminary evidence. The authors clearly define the trial as a pilot study. They computed that, according to the hypothesis, they needed 3946 patients with acute coronary syndromes to have reasonable odds to show a difference in clinical outcomes between patients treated with roxithromycin and those treated with placebo. Instead, they recruited 202 patients. The total number of observed outcomes as defined in the study protocol was 10. The difference in outcome rates is marginally significant, but this could have occurred by chance alone.

Hence, the strength of evidence of the study findings is, at best, very low. Further large-scale trials are required. Until that time, antibiotics for coronary disease should remain on the shelves of research laboratories.

Jean-Pierre Boissel, MD
Hôpital Neuro-CardiologiqueLyon, France

Jean-Pierre Boissel, MD
Hôpital Neuro-Cardiologique
Lyon, France


References

1. Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link? Lancet. 1997;350:430-6.

2. Kuo CC, Shor A, Campbell LA, et al. Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. J Infect Dis. 1993;167:841-9.

3. Saikku P, Leinonen M, Tenkanen L, et al. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki heart study. Ann Intern Med. 1992;116:273-8.

4. Gupta S, Leatham EW, Carrington D, et al. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation. 1997;96:404-7.