Abstract

Background: Hepatorenal syndrome type 1 (HRS-1) is a rapidly progressive form of renal failure associated with high mortality in patients (pts) with decompensated cirrhosis and ascites. The FDA-approved vasopressin analogue, terlipressin (terli), improves renal function in pts with HRS-1 by reducing portal hypertension and increasing effective arterial volume and mean arterial pressure (MAP)—a marker of the hemodynamic response to treatment. Using the largest-to-date, prospective database of terli for the treatment of HRS, this subgroup analysis compared the change in MAP (ΔMAP) from baseline (BL) to the end of treatment (EOT) based on HRS reversal status and treatment group.

Methods: Pooled data from the safety population (ie, treated pts) from 3 Phase III studies (OT-0401, REVERSE, and CONFIRM) were used to compare HRS reversal (defined as a serum creatinine ≤1.5 mg/dL while on treatment, by EOT or discharge), and ΔMAP from BL to EOT (Day 0 to Day 14) by HRS reversal status and treatment group. MAP was averaged daily, before and 2 hours post-injection (4 per day) of terli or placebo (pbo); if data were missing, the last observation was used. Associated P values were determined via a chi-square test (HRS reversal), ANOVA and Kruskal-Wallis test (ΔMAP by HRS reversal status), or a Wald test (odds ratio determined via logistic regression analysis).

Results: In the pooled population (N=598), 349 pts received terli and 249 pts received pbo. HRS reversal was achieved by more pts treated with terli than pbo (34% [117/349] vs 17% [42/249], P<.001). Mean MAP (± SD, mm Hg) at BL was similar between pts who achieved HRS reversal and those who did not, regardless of treatment (terli, 77 ± 11 vs 78 ± 13; pbo, 79 ± 10 vs 76 ± 11; Figure); whereas, pts who achieved HRS reversal had a significant ΔMAP (mean ± SD, mm Hg) from BL to EOT versus those with no HRS reversal (terli, +7 ± 11 vs +2 ± 13, P=.001; pbo, +3 ± 9 vs -3 ± 11, P<.001; Figure). A ΔMAP of ≥5 mm Hg was significantly associated with HRS reversal (odds ratio [95% confidence interval]: terli, 2.427 [1.531–3.846] P<.001; pbo, 2.545 [1.282–5.051] P=.008), regardless of treatment.

Conclusion: In this analysis, significantly more terli-treated pts than pbo-treated pts achieved HRS reversal. A greater increase in MAP from BL to EOT was noted among those pts who achieved HRS reversal, with an increase in MAP of ≥5 mm Hg significantly associated with the odds of achieving HRS reversal, regardless of treatment.