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 (similar to 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.