ANALYSIS OF THE TREATMENT EFFECT ON RECURRENT BLEEDING AND DEATH IN PATIENTS WITH CIRRHOSIS AND ESOPHAGEAL-VARICES - MULTISTAGE COMPETING-RISKS MODEL COMPARED TO CONVENTIONAL METHODS

Background/Aims: Multiple recurrences of bleeding with high mortality in cirrhosis with esophageal varices have been inadequately analyzed i n previous trials, We propose analysis by the multistage competing ris ks model, specifying the effect on overall mortality as an effect on m ortality during bleeding, rate of cessation of bleeding, mortality rat e without bleeding, and rate of rebleeding, Methods: The Copenhagen Es ophageal Varices Project enrolled patients after first bleeding and ra ndomized 94 to usual treatment and 93 to sclerotherapy as supplement, During 9-52 months of follow-up, rebleeding occurred in 49 and 42, and death in 68 and 60 patients, respectively, The proportional hazards r egression model (Cox model) was used for reanalysis both by the multis tage competing-risks model and by conventional analysis for overall mo rtality and rate of first rebleeding, In the multistage model, time ze ro was at entry to any new disease stage, of which the first four were analyzed - two bleeding stages and two bleeding-free stages. Results: The conventional analysis showed a reduction of overall mortality rat e in the sclerotherapy group of borderline significance, but no effect on rate of rebleeding, The multistage model indicated that sclerother apy reduced the rate of rebleeding late in the disease course, and par ticularly after the first rebleeding, Rate of cessation of bleeding an d mortality rates during bleeding and without bleeding were not affect ed by sclerotherapy, Conclusions: Conventional analysis may give misle ading conclusions, which might be avoided by applying the multistage m odel, The effect of sclerotherapy on overall mortality may be ascribed entirely to the reduced rate of rebleeding.