Original ResearchFull Report: Clinical—LiverAddition of Simvastatin to Standard Therapy for the Prevention of Variceal Rebleeding Does Not Reduce Rebleeding but Increases Survival in Patients With Cirrhosis
Section snippets
Study Design and Oversight
The BLEPS (Bleeding Prevention With Simvastatin) study was an investigator-initiated multicenter, randomized (1:1), placebo-controlled, double-blind, parallel group trial that enrolled patients from 14 Spanish academic centers. The study protocol and amendments were approved by the Spanish national regulatory authority and the Institutional Review Board or Ethics Committee for Clinical Research at each participating center and the coordinating center. Written informed consent was obtained from
Results
The study enrolled 158 participants who were randomized a median of 6 days after the index bleeding (interquartile range [IQR], 5–7 days). Eighty-three were assigned to receive placebo and 75 simvastatin. Supplementary Figure 1 shows the disposition of the patients. During the data blind review, 9 patients were excluded from the safety population (n = 149) because they never received the study medication (6 consent withdrawal before starting treatment, 1 immediate death, 1 immediate rebleeding,
Discussion
In this multicenter double-blind randomized trial in patients with cirrhosis after variceal bleeding, treatment with simvastatin resulted in longer survival than placebo administration (given above standard of care therapy). Simvastatin, however, failed to show superiority over placebo in decreasing the rate of rebleeding or other complications of cirrhosis. The increase in survival achieved by simvastatin was mainly determined by a decrease in mortality derived from rebleeding and infections,
Acknowledgments
The authors acknowledge the following: Data safety monitoring board: J. A. Arnaiz, A. Berzigotti, Jose Rios (statistician). Administrative, technical, or material support: Study supervision: J. A. Arnaiz. Trial manager: J. Pich.
Additional BLEPS Study Investigators: Hospital Vall d’Hebron (Barcelona): Salvador Augustin; Hospital Puerta de Hierro (Madrid): Elba Llop; Hospital Universitario de Canarias (Tenerife): Dalia Morales Arraez, Goretti Hernández Mesa; Hospital Ramon y Cajal (Madrid):
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Conflicts of interest The authors disclose no conflicts.
Funding The Spanish Ministry of Health funded the trial through a competitive peer-reviewed grant. The funding agency had no role in the collection, analysis, or interpretation of the data.
Author names in bold designate shared co-first authorship.
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Authors share co-first authorship.