Cyclosporine is an immunosuppressive agent discovered in 1972. It was first used to prevent rejection after organ transplantation and more recently, for management of autoimmune diseases. Common side effects associated with cyclosporine therapy are nephrotoxicity and hypertension. To observe the magnitude of elevated blood pressure caused by cyclosporine compared to placebo, we searched the available scientific literature. We identified 17 trials that met our inclusion criteria and had extractable data.
This systematic review found an important increase in blood pressure for patients treated with cyclosporine with a best estimate of the overall magnitude of 7 mmHg. A dose-related effect was also observed, with an average increase in mean blood pressure ranging from 5 mmHg with low doses to 11 mmHg with high doses of cyclosporine. This increase is of clinical importance and suggests that prescribers should try to find the lowest effective dose in all patients on chronic therapy.
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Cyclosporine is an immunosuppressive agent used for different autoimmune diseases. The official Canadian indications for cyclosporine are solid organ transplantation, bone marrow transplantation, psoriasis, rheumatoid arthritis and nephritic syndrome (e-CPS 2008). The expanding range of indications for cyclosporine therapy will lead to more patients receiving chronic therapy with possible side effects, hypertension being one of the most common. Therefore it is essential to know the magnitude of increase of blood pressure (BP) associated with cyclosporine in order to appropriately manage patients receiving the drug.
Objectifs
The primary objective of this systematic review is to evaluate the effect of cyclosporine on blood pressure, compared to placebo in randomized trials.
Stratégie de recherche documentaire
We searched The Cochrane Central Register of Controlled Trials (CENTRAL) and bibliographic databases, including MEDLINE (2000-2008) and EMBASE (1980-2008).
Critères de sélection
Selection was made using double-blind, randomized, controlled trials comparing cyclosporine to placebo. All patients treated with cyclosporine were included without restriction by type of disease or by age and sex.
Recueil et analyse des données
Blood pressure measurements in any setting and by any means were acceptable including the auscultatory or oscillometric method with a preference for the sitting position. Mean blood pressure results were entered as mean change from placebo and standard error of the mean (SEM). If blood pressure data was provided at different times after the initiation of cyclosporine therapy the weighted mean BP change from placebo from all measurements was used.
Résultats principaux
The search yielded 1340 citations, of which 17 trials met the inclusion criteria. We created dose-ranges according to the usual dose administration recommended by the manufacturer and allocated the 17 included trials to the corresponding dose-range. The results demonstrate a highly statistically significant increase in blood pressure associated with cyclosporine. There appears to be a dose-related effect with lower doses (1-4 mg/kg/d) increasing mean BP by an average of 5 mmHg and higher doses (>10 mg/kg/d) increasing mean BP by 11 mmHg on average. Furthermore in 3 trials the effect appears to be similar after a single dose as with chronic therapy.
Conclusions des auteurs
Cyclosporine statistically significantly increases blood pressure compared to placebo in a dose-related fashion. The magnitude of increase in blood pressure is clinically significant and increases the risk of stroke, myocardial infarction, heart failure and other adverse cardiovascular events associated with elevated BP. Consequently prescribers should try to find the lowest effective dose in all patients receiving cyclosporine chronically.
