Tolvaptan and its potential in the treatment of hyponatremia

Figures & data

Table 1 Short-term effects of tolvaptan on congestive heart failure

Study	Treatment	Weight loss (kg)	Weight loss (kg)	Urine output (L/day)	Urine osmolality (mOsm/kg)	Change in Sna (meq/L)	Change in Sna (meq/L)
		Day 1	Day 7	Day 1	Day 1	Day 1	Day 7
Tolvaptan in patients with CHF	Tolvaptan
	30 mg	0.79 ± 0.99		3.9 ± 0.6	15.5 ± 190
	45 mg	0.96 ± 0.93		4.2 ± 0.9	52.4 ± 165
	60 mg	0.84 ± 0.02		4.6 ± 0.4	118.8 ± 132
	Placebo	+0.32 ± 0.46		2.3 ± 0.2	+135.8 ± 189
ACTIV in CHF	Tolvaptan
	30 mg	1.80 (−3.85 to −0.5)				+2.77
	60 mg	2.10 (−3.1 to −0.85)				+3.38
	90 mg	2.05 (−2.80 to −0.6)				+3.50
	Placebo	0.60 (−1.60 to 0)				0.20
EVEREST	Tolvaptan
	30 mg
	Trial A	1.71 ± 1.8	3.35 ± 3.3			+3.28	+2.07
	Trial B	1.82 ± 2.01	3.77 ± 3.6
	Placebo A	0.99 ± 1.83	2.73 ± 3.3			0.41	1.06
	Placebo B	0.95 ± 1.85	2.79 ± 3.5

All above comparisons of tolvaptan versus placebo are statistically significant (p < 0.05).

Abbreviation: CHF, congestive heart failure.

Table 2 Long-term effects of tolvaptan on congestive heart failure

Study	Event	Tolvaptan 30 mg	Placebo	p value
ACTIV in CHF	Death	13/239 (5.4%)	7/80 (8.7%)	0.18
	Rehospitalization	44/239 (18.4%)	14/80 (17.5%)	>0.99
	Worsening CHF	64/239 (26.7%)	22/80 (27.5%)	0.88
EVEREST	All-cause mortality	537/2063 (25.9%)	543/2055 (26.3%)	0.68
	CV death or hospitalization for CHF	871/2063 (42.0%)	829/2055 (40.2%)	0.55
Effect of tolvaptan on LV dilation	Death	6/120 (5%)	11/120 (9%)	0.03
	CHF-related hospitalizations	21/120 (18%)	34/120 (28%)
	Post-LVEDI	1.78 ± 10.7	0.04 ± 10.0	0.21

Duration: ACTIV in CHF study: 60 days; EVEREST study: 9.9 months; and Udelson’s Effect of Tolvaptan on LV Dilation and Function: 52 weeks.

Abbreviations: CHF, congestive heart failure; CV, cardiovascular; LVEDVI, left ventricular end diastolic volume index.