The role of tolvaptan add-on therapy in patients with acute heart failure: a systematic review and network meta-analysis

Vireza Pratama1,2,3*, Jordan Budiono4, Jarir At Thobari5,6, Bambang Widyantoro7, Vita Yanti Anggraeni8 and Lucia Kris Dinarti9

1Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia, 2Department of Cardiology, Gatot Soebroto Central ArmyHospital (RSPAD), Jakarta, Indonesia, 3Department of Cardiology and Vascular Medicine, Faculty of Medicine and Health Science, Universitas Pertahanan Republik Indonesia, Bogor, Indonesia, 4Faculty of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia, 5Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia, 6Clinical Epidemiology and Biostatistics Unit (CEBU), Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia, 7Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Indonesia, National Cardiovascular Center Harapan Kita, Jakarta, Indonesia, 8Department of Internal Medicine, Division of Cardiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia, 9Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia

Background: Several conflicting reviews have concluded that using loop diuretics is associated with poorer clinical and safety outcomes. Therefore, this study aimed to investigate the efficacy and safety of tolvaptan as an adjunct to conventional diuretic therapy in patients with acute heart failure (AHF).

Methods: A comprehensive search was conducted on PubMed, Embase, ProQuest, EBSCO, and Cochrane Library until 24 May 2023 to identify randomized controlled trials that compared the effects of tolvaptan with conventional therapy and placebo in patients with AHF. The quality assessment of the included trials was conducted using the Cochrane risk of bias. A network meta-analysis (NMA) was conducted to examine the effect of tolvaptan on dosage.

Result: 17 studies were selected, with 18 reports involving 10,039 patients. The tolvaptan add-on therapy significantly alleviated dyspnea [24 h: RR 1.16 (1.04, 1.29), 48 h: RR 1.18 (1.04, 1.33)], reduced body weight within 48 h [Asian group, MD −0.93 (−1.48, −0.38); non-Asian group, MD −2.76 (−2.88, −2.65)], reduced edema [RR 1.08 (1.02, 1.15)], increased serum sodium [non-Asian group, MD 3.40 (3.02, 3.78)], and resulted in a change in serum creatinine [MD −0.10 (−0.18, −0.01)]. No significant differences were observed in mortality and rehospitalization. The NMA suggested that an intermediate dosage (15 mg/day) might offer the best efficacy in reducing dyspnea within 24 h, reducing edema, increasing serum sodium, and lowering the incidence of worsening renal function (WRF).

Conclusion: In conclusion, the meta-analysis showed that tolvaptan contributed to the short-term alleviation of congestive symptoms, elevated sodium levels, and a lower incidence of WRF. However, no significant benefits were observed in long-term symptoms, rehospitalization rates, or mortality. An intermediate tolvaptan dosage might be the optimal choice for various clinical outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42023420288)