Antibiotic use in secondary prevention of cardiovascular disease: A pharmacoepidemiology study

Background. Several trials of antibiotic use for the secondary prevention of cardiovascular diseases have been performed but individual studies have produced conflicting and inconclusive results. Therefore, we performed a systematic review of published studies to synthesize the evidence. We also examined a large cohort of previously revascularized patients to assess if a small but meaningful benefit of antibiotic exists.; Research question. Whether antibiotic use, compared to non-use, can reduce future cardiovascular events in a population of previously revascularized patients.; Method. A meta-analysis and a nested case control study were both conducted to answer the research question. In the meta-analysis, PubMed and the Cochrane Central Registry of controlled trials were searched for studies published between January 1 1994 and December 31 2004 using keyword 'antibiotic use' and 'cardiovascular diseases'. 232 published papers were initially identified and 12 randomized trials meet our inclusion criteria. The data were combined using a random effects model. A sensitivity analysis with a fixed effects model was also performed. Our nested case control study was conducted on a cohort of all individuals ≥65 years of age who had a revascularization procedure from 1995 to 2000 and were registered in the Quebec universal health databases. The discharge date of each patient after revascularization was date of cohort entry. The primary endpoint was a composite of death, myocardial infraction and repeat revascularization. For each case, five controls were randomly selected and matched by date of cohort entry and age to the cases. Current users of antibiotics, those whose last prescription overlapped with the index date, were compared to individuals who were not exposed to antibiotics in the year preceding the event. Similarly the risk of recent (1-6 month) and past (6-12 months) antibiotic exposure was estimated. Odds ratios were calculated by using conditional logistic regression and adjusted for potential confounders.; Results. Our meta-analysis identified the 12 studies which randomized 10 231 patients to antibiotic treatment and 10 144 patients to control. The odds ratio for the composite event endpoint of death, myocardial infarction or revascularization was 0.92 (95CI%: 0.84-1.02). A similar result was found using a fixed effect model. No evidence for publication bias was found. Our nested case control study included 6 117 cases and 30 573 controls. The adjusted odds ratios of cardiac events for any current, recent and past antibiotic use were 1.12 [95%CI: 0.98-1.29], 1.21[95%CI: 1.07-1.28] and 1.31 [95%CI: 1.15-1.48], respectively.; Conclusion. No prevention association between antibiotic use and future cardiovascular events was shown either in the meta-analysis or our nested case control study. On the contrary, our nested case control study suggested increased risk long term following antibiotic exposure. One hypothesis to explain these results is that antibiotic exposure is a surrogate marker for a heightened inflammatory status that is associated with later cardiovascular risk.