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. 2024 May 30:11:1367442.
doi: 10.3389/fcvm.2024.1367442. eCollection 2024.

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

Vireza Pratama  1   2   3 , Jordan Budiono  4 , Jarir At Thobari  5   6 , Bambang Widyantoro  7 , Vita Yanti Anggraeni  8 , Lucia Kris Dinarti  9
Affiliations

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

Vireza Pratama et al. Front Cardiovasc Med. .

Abstract

Background: Several conflicting reviews have concluded that the use of 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 dosage effect of tolvaptan.

Result: A total of 17 studies with 18 reports, involving 10,039 patients, were selected. 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, and mortality. An intermediate dosage of tolvaptan might be considered the optimal choice for various clinical outcomes.

Systematic review registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42023420288).

Keywords: acute heart failure; heart failure; network meta-analysis; systematic review; tolvaptan.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart showing the eligibility of studies for inclusion in the updated meta-analysis.
Figure 2
Figure 2
Forest plot depicting the effects of add-on tolvaptan on clinical outcomes. The effects of add-on tolvaptan on dyspnea relief within 24 h (A), dyspnea relief within 48 h (B), changes in body weight within 48 h (C), changes in body weight within 7 days (D), edema reduction (E), changes in serum sodium (F) and creatinine (G) levels, mortality (H), and rehospitalization (I).
Figure 3
Figure 3
Network meta-analysis (NMA) on the tolvaptan dosage effect subgroup analysis. Contrast plot showing the dosage effect of each efficacy and safety indicator. (A) Network analysis contrast plot of dyspnea within 24 h; (B) network analysis contrast plot of dyspnea within ≥48 h; (C) network analysis contrast plot of reduced body weight within 48 h; (D) network analysis contrast plot of reduced body weight within 7 days; (E) network analysis contrast plot of edema; (F) network analysis contrast plot of serum sodium level; (G) network analysis contrast plot of serum creatinine level; and (H) network analysis contrast plot of mortality.
Figure 4
Figure 4
Contour-enhanced funnel plot and heat map for each efficacy and safety indicator.
See this image and copyright information in PMC

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