Randomized Secondary Prevention Trial of Azithromycin in Patients With Coronary Artery Disease

Abstract

Background-Chlamydia pneumoniae is associated with coronary artery disease (CAD), although its causal role is uncertain. A small preliminary study reported a Ͼ50% reduction in ischemic events by azithromycin, an antibiotic effective against C pneumoniae, in seropositive CAD patients. We tested this prospectively in a larger, randomized, double-blind study. Methods and Results-CAD patients (nϭ302) seropositive to C pneumoniae (IgG titers Ն1:16) were randomized to placebo or azithromycin 500 mg/d for 3 days and then 500 mg/wk for 3 months. The primary clinical end point included cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction (MI), stroke, unstable angina, and unplanned coronary revascularization at 2 years. Treatment groups were balanced, and azithromycin was generally well tolerated. During the trial, 47 first primary events occurred (cardiovascular death, 9; resuscitated cardiac arrest, 1; MI, 11; stroke, 3; unstable angina, 4; and unplanned coronary revascularization, 19), with 22 events in the azithromycin group and 25 in the placebo group. There was no significant difference in the 1 primary end point between the 2 groups (hazard ratio for azithromycin, 0.89; 95% CI, 0.51 to 1.61; Pϭ0.74). Events included 9 versus 7 occurring within 6 months and 13 versus 18 between 6 and 24 months in the azithromycin and placebo groups, respectively. Conclusions-This study suggests that antibiotic therapy with azithromycin is not associated with marked early reductions (Ն50%) in ischemic events as suggested by an initial published report. However, a clinically worthwhile benefit (ie, 20% to 30%) is still possible, although it may be delayed. Larger (several thousand patient), longer-term (Ն3 to 5 years) antibiotic studies are therefore indicated. (Circulation. 2000;102:1755-1760.)

Reduced Progression of Early Carotid Atherosclerosis After Antibiotic Treatment and Chlamydia pneumoniae Seropositivity

“…Reductions in CRP and other inflammatory markers were also observed in prior antibiotic trials. 32,33 The reduced IMT progression after roxithromycin therapy in Cp seropositivity may be explained by several beneficial effects of antibiotic treatment on early atherosclerotic formation, such as those attributable to a reduced smooth muscle cell proliferation or a decreased smooth muscle cell migration from the media and adventitia into the intima, a reduced lipid accumulation, an improvement of endothelial function, and a diminished inflammatory activity. 3 In our investigation, the combined frequency of stroke, myocardial infarction, or vascular death was not diminished during the 2 years of follow-up by roxithromycin.…”

Effect of Treatment for Chlamydia pneumoniae and Helicobacter pylori on Markers of Inflammation and Cardiac Events in Patients With Acute Coronary Syndromes

“…At 3 and 6 months after recruitment, a reduction in a composite measure of inflammatory markers was found, but there was no change in cardiac event rate. 12 Therefore, antibiotic treatment may be more effective in ACS and could play a role in stabilizing unstable plaques. This possibility is supported not only by the present study and the ROXIS study 9 but also by a recently published trial of clarithromycin in acute non-Q-wave coronary syndromes.…”

Influenza and Cardiovascular Disease

“…6 -13 Antibiotic therapy for C. pneumoniae in CVD patients has been tried with transient or no benefit to date. 14,15 Ongoing studies may give a definitive answer by late 2003. 16 Here, we review recent studies suggesting influenza may play a role in atherogenesis or atherothrombosis.…”