Preventing post-organ transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapies.
BACKGROUND: Cytomegalovirus (CMV) causes significant morbidity and mortality in transplant recipients, but there is no consensus regarding the most appropriate prevention method. The goal of this meta-analysis was to compare the efficacy of universal prophylaxis and preemption using ganciclovir. METHODS: Literature searches for randomized and nonrandomized controlled trials of ganciclovir prophylaxis and preemption were conducted. Because of the lack of head-to-head trials, indirect comparisons of meta-analyses of the prevention strategies were performed. Meta-analyses were conducted using a random effects model to estimate the overall risk ratios for various clinical outcomes. We assessed the event rates for control groups across the trials for comparability. RESULTS: Literature searches identified 17 universal prophylaxis trials and 9 preemption trials with 1560 and 457 subjects, respectively. Overall event rates for CMV disease in control groups across the studies were similar (approximately 26%). The relative risk of CMV disease in prophylaxis trials was 0.34 (95% confidence interval, 0.24-0.48) when trials of patients with prophylaxis of short duration and trials that only evaluated patients with high-risk serostatus were excluded. The relative risk of CMV disease for study subjects in all preemption trials was 0.30 (95% confidence interval, 0.15-0.60), compared with that for control subjects. There was no statistically significant difference in CMV disease between prevention strategies. Similarly, no differences between strategies were found for all-cause mortality or rejection. There were insufficient data to adequately evaluate graft loss and opportunistic infection. CONCLUSIONS: On the basis of indirect comparisons of meta-analyses of prevention strategies, universal prophylaxis and preemption are equally effective in reducing the incidence of CMV disease.