Effect of Treatment for Chlamydia pneumoniae and Helicobacter pylori on Markers of Inflammation and Cardiac Events in Patients with Acute Coronary Syndromes. South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina Pectoris (STAMINA). - STAMINA

Description:

The goal of this study was to assess the safety and efficacy of antibiotic treatment targeted to Chlamydia pneumoniae (CP) and Helicobacter pylori (HP)among patients discharged following acute coronary syndromes (ACS).

Study Design

Study Design:

Patients Enrolled: 325

Drug/Procedures Used:

325 patients with ACS (unstable angina, or MI) were eligible for the double blind placebo controlled study if they had not taken antibiotics for 3 months. Patients were randomized to 1 of 3 treatment regimens for 1 week: 1) amoxicillin (1 g BID), omeprazole (20mg BID), metronidazole (400mg BID) (effective for HP), 2) azithromycin (500mg daily for 3 days), and 7 days of omeprazole and metronidazole (effective for HP and CP), or 3) placebo. Follow-up was 1 year and those requiring subsequent antibiotics were excluded.

Principal Findings:

325 patients (225 male) completed the course of antibiotics, 27% had cardiac events, 16 took subsequent antibiotics, and 17 underwent elective coronary revascularization. Seropositivity for H. pylori was 51% and for C. pneumoniae 41%. Improved event-free survival was observed among patients treated with amoxicillin (p = 0.04), azithromycin regimens (p = 0.061), and when active treatment groups were combined (p = 0.02) compared to placebo. By 52 weeks, a coronary event occurred in 26% of patients in the antibiotic groups vs. 39% of patients in the placebo arm, RR 0.6 (95% CI 0.37-0.99). The dominant effect was a reduction in hospitalization for unstable angina with no difference in mortality. The benefit was independent of entry HP and CP seropositivity. CRP levels were reduced in those with unstable angina but not MI with amoxicillin, but fibrinogen was reduced by both antibiotics (p = 0.06).

Interpretation:

Among patients with acute coronary syndromes, antibiotic treatment for one week was associated with a reduction in adverse cardiac events, but the benefit was independent of H. pylori or C. pneumoniae seropositivity. The association of one week of antibiotic therapy with a reduction in long term cardiac events is remarkable but is not consistent with other studies. How can these findings be reconciled? The study was conducted in a relatively low socioeconomic area in England, where participants may have had other chronic infections such as bronchitis and periodontal disease that benefit from antibiotics and increase the risk of coronary events. The report and analysis did not contain information regarding management of other risk factors, and use of evidence based therapies (ASA, statins, ACEi, beta blockers) that could influence the outcome. The study sample size was also rather small. Further prospective trial assessing this hypothesis in a prospectrive fashion using prolonged antibiotic administration are underway.

References:

Stone AFM, Mendall MA, Kaski JC, et al. Effect of Treatment for Chlamydia pneumoniae and Helicobacter pylori on Markers of Inflammation and Cardiac Events in Patients with Acute Coronary Syndromes. South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina Pectoris (STAMINA). Circulation 2002;106:1219-23.

Keywords: Coronary Artery Disease, Acute Coronary Syndrome, Follow-Up Studies, Periodontal Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Disease-Free Survival, Azithromycin, Risk Factors, Metronidazole, Omeprazole, Chlamydophila pneumoniae, Bronchitis, Helicobacter pylori, Fibrinogen


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