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Br J Clin Pharmacol ; 78(1): 24-32, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24251918

RESUMO

AIMS: Calcineurin inhibitors (CNIs) taken after heart transplantation lead to excellent short-term outcomes, but long-term use may cause chronic nephrotoxicity. Our aim was to identify, appraise, select and analyse all high-quality research evidence relevant to the question of the clinical impact of CNI-sparing strategies in heart transplant patients. METHODS: We carried out a systematic review and meta-analysis of randomized controlled trials on CNI reduction in heart transplant recipients. Primary outcomes were kidney function and acute rejection after 1 year. Secondary outcomes included graft loss, all-cause mortality and adverse events. RESULTS: Eight open-label studies were included, with 723 patients (four tested de novo CNI reduction and four maintenance CNI reduction). Calcineurin inhibitor reduction did not improve creatinine clearance at 12 months 5.46 [-1.17, 12.03] P = 0.32 I(2) = 65.4%. Acute rejection at 12 months (55/360 vs. 52/332), mortality (18/301 vs. 15/270) and adverse event rates (55/294 vs. 52/281) did not differ between the low-CNI and standard-CNI groups. There was significant benefit on creatinine clearance in patients with impaired renal function at 6 months [+12.23 (+5.26, +18.82) ml min(-1) , P = 0.0003] and at 12 months 4.63 [-4.55, 13.82] P = 0.32 I(2) = 75%. CONCLUSIONS: This meta-analysis did not demonstrate a favourable effect of CNI reduction on kidney function, but there was no increase in acute rejection. To provide a better analysis of the influence of CNI reduction patterns and associated treatments, a meta-analysis of individual patient data should be performed.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Rejeição de Enxerto/induzido quimicamente , Transplante de Coração , Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Complicações Pós-Operatórias/induzido quimicamente , Inibidores de Calcineurina/uso terapêutico , Causas de Morte , Creatinina/metabolismo , Relação Dose-Resposta a Droga , Rejeição de Enxerto/epidemiologia , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Humanos , Nefropatias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto
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