Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study).

Sakaida, Isao; Terai, Shuji; Kurosaki, Masayuki; Okada, Mitsuru; Hirano, Takahiro; Fukuta, Yasuhiko

BACKGROUND This large-scale post-marketing surveillance study (START study) evaluated the effectiveness and safety of tolvaptan in Japanese liver cirrhosis patients with hepatic edema in real-world clinical settings. Here, we present the final analysis outcomes. METHODS A prospective, multicenter, non-interventional study involving patients who received tolvaptan for the treatment of liver cirrhosis with hepatic edema with an insufficient response to conventional diuretics. The observation period was up to 6 months. Effectiveness evaluation included changes in body weight and clinical symptoms. Safety analysis included evaluation of adverse drug reactions (ADRs). RESULTS Case reports of 1111 patients were collected. Of these, 1109 were included in the safety analysis and 1098 in the effectiveness analysis. The mean age was 69.4 ± 11.5 years and 695 (62.7%) patients were male. After tolvaptan treatment, a decrease in body weight from baseline was - 2.6 ± 2.7 kg on day 7 and - 3.8 ± 4.1 kg on day 14. Moreover, clinical symptoms significantly improved over the 14-day treatment. Frequently reported ADRs were thirst (6.6%), hepatic encephalopathy (2.3%), dehydration (1.5%), and hypernatremia (1.2%). A serum sodium level of ≥ 150 mEq/L was reported in five patients (0.5%). Multivariate analyses showed that the baseline blood urea nitrogen (BUN) level (cut-off value: 22.4 mg/dL) was the predictive factor for tolvaptan treatment response. CONCLUSIONS The results suggest that tolvaptan was effective and well-tolerated in liver cirrhosis patients with hepatic edema. In the real-world clinical setting, tolvaptan provides a useful option for the treatment of hepatic edema.