Efficacy of oral tolvaptan in acute heart failure patients with hypotension and renal impairment.
OBJECTIVE
Although congestion is the main reason for admission in patients with worsening acute heart failure syndromes, patients presenting with low SBP and renal impairment often do not respond adequately to and may not tolerate traditional diuretic therapy. We sought to determine the short-term hemodynamic effects of tolvaptan in this high-risk population.


METHODS
In a subset analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial, 759 patients (18% of total) had elevated blood urea nitrogen (BUN) (> 20  mg/dl) and low SBP (<105  mmHg) at admission. Of these, 386 were randomized to tolvaptan and 373 to placebo.


RESULTS
Demographics and baseline characteristics were similar in both groups. Greater reductions from baseline in body weight were observed for tolvaptan (1.63 ±  2.00 vs. 0.76  ±  1.75  kg, P  <  0.0001 at day 1 and 3.23  ±  3.36 vs. 2.10  ±  3.47  kg, P  <  0.0001 at day 7 or discharge). Greater increases in serum sodium concentration were also observed in the tolvaptan group as early as day 1 (4.41  ±  3.67 vs. 1.32  ±  3.93  mEq/l, P  <  0.0001) and persisted through day 7 or discharge (4.79  ±  4.89 vs. 1.25  ±  5.00  mEq/l, P  <  0.0001). Similarly, improvements in patient-reported dyspnea and investigator-assessed orthopnea were significantly greater in the tolvaptan group as early as day 1 of treatment. These changes were not associated with significant differences in heart rate, SBP, DBP or serum creatinine between patients in the two treatment groups during hospitalization. In-hospital mortality rates (total and cause-specific) were comparable to patients who had presented with SBP more than 105  mmHg and BUN less than 20  mg/dl.


CONCLUSIONS
In this subgroup analysis of patients with hypotension and renal impairment, tolvaptan improved symptoms, reduced body weight and increased serum sodium as early as inpatient day 1 without adversely affecting blood pressure or renal function.
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Muthiah
M
Vaduganathan
Mihai
M
Gheorghiade
Peter S
PS
Pang
Marvin A
MA
Konstam
Faiez
F
Zannad
Karl
K
Swedberg
Liliana
L
Grinfeld
John C
JC
Burnett
Holly B
HB
Krasa
Christopher
C
Zimmer
John
J
Blair
John
J
Ouyang
Aldo P
AP
Maggioni
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007022:Hypotension / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000209:etiology*; D012964:Sodium / Q000097:blood; D000077602:Tolvaptan; D016896:Treatment Outcome
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D002317:Cardiovascular Agents; D004232:Diuretics; D000077602:Tolvaptan; D005665:Furosemide; D012964:Sodium