To the Editor:
There is a growing body of literature showing that left ventricular assist device (LVAD) provides incomplete compensation of either left or right ventricular failure.1 This explains that above 50% of patients still require loop diuretics even 2 years after LVAD implantation, although in substantially lower doses than before the LVAD.2 Currently, there is no indication that loop diuretics are the best drugs to provide optimization of volume status on LVAD support. As Imamura et al.3 discussed in the letter to the editor, vasopressin type-2 receptor antagonist, tolvaptan, may be used to spare loop diuretics use or dose in patients with LVAD.
Vasopressin antagonists have been investigated as a potential alternative or addition to loop diuretics in heart failure for a long time. The meta-analysis of randomized controlled trials showed that tolvaptan significantly reduced body weight and improved hyponatremia compared with placebo group but did not significantly improve long-term clinical outcomes such as all-cause mortality or cardiac event rate.4 Additionally, the study by Konstam et al.5 showed that the use of tolvaptan only marginally decreased loop diuretic doses from 154 to 141 mg over 3 days in patients with acute heart failure.
The cost of vasopressin antagonist is a concern as well. A cost-effectiveness analysis of tolvaptan in patients hospitalized for acute decompensated heart failure and hyponatremia showed that tolvaptan short-term therapy was cost-effective against fluid restriction because of shorter length of hospitalization in patients on tolvaptan therapy which offset tolvaptan pharmacy cost.6 However, considering tolvaptan for chronic use of ambulatory LVAD patient is still challenging. Tolvaptan is more expensive than furosemide (tolvaptan 30 mg average wholesale price of $534.46 per each tablet7vs. furosemide 40 mg $1.00 per each tablet8), which may limit its utilization for long-term therapy.
In terms of tolvaptan use in patients with LVAD, the clinical literature is very limited—in fact, there is one case report.9 Besides, current indications to vasopressin antagonists are limited to the patients with hypervolemic or euvolemic hyponatremia which is uncommon after LVAD.
In summary, we agree that tolvaptan may be worth trying, but we do not see a compelling evidence to substitute tolvaptan for loop diuretics in patients with LVAD because there is no clinical literature showing long-term efficacy and safety and cost-effectiveness of tolvaptan use in patients with LVAD.
Department of Pharmacy Practice South Dakota State University Sioux Falls, South Dakota
Department of Pharmacy
Avera McKennan Hospital Sioux Falls, South Dakota
University of Kentucky HealthCare, Division of Cardiology, Gill Heart Institute Lexington, Kentucky
1. Uriel N, Sayer G, Addetia K, et al. Hemodynamic ramp tests in patients with left ventricular assist devices. JACC Heart Fail 2016.4: 208–217.
2. Kido K, George B, Charnigo RJ, Macaulay TE, Brouse SD, Guglin M. Chronologic changes and correlates of loop diuretic dose in patients with left ventricular assist device. ASAIO J 2017.63: 774–780.
3. Imamura T. Does tolvaptan have any therapeutic roles in patients with left ventricular assist device? ASAIO J 2019.65: e78.
4. Xiong B, Huang Y, Tan J, et al. The short-term and long-term effects of tolvaptan in patients with heart failure: A meta-analysis of randomized controlled trials. Heart Fail Rev 2015.20: 633–642.
5. Konstam MA, Kiernan M, Chandler A, et al.; SECRET of CHF Investigators, Coordinators, and Committee Members: Short-term effects of tolvaptan in patients with acute heart failure and volume overload. J Am Coll Cardiol 2017.69: 1409–1419.
6. Dasta JF, Sundar S, Chase S, Lingohr-Smith M, Lin J. Economic impact of tolvaptan treatment vs. fluid restriction based on real-world data among hospitalized patients with heart failure and hyponatremia. Hosp Pract (1995) 2018.46: 197–202.
7. Kimura M, Nawata K, Kinoshita O, et al. Successful treatment of intractable fluid retention using tolvaptan after treatment for postoperative mediastinitis in a patient with a left ventricular assist device. Int Heart J 2015.56: 574–577.
8. Tolvaptan: Lexi-Comp OnlineTM
. November 25, 2018.Lexi-Comp, Inc..
9. Furosemide: Lexi-Comp OnlineTM
. November 25, 2018.Lexi-Comp, Inc..