Article

Efficacy of oral tolvaptan in acute heart failure patients with hypotension and renal impairment

Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Journal of Cardiovascular Medicine (Impact Factor: 1.41). 07/2012; 13(7):415-22. DOI: 10.2459/JCM.0b013e328355a740
Source: PubMed

ABSTRACT 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.
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.
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.
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.

0 Followers
 · 
230 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and Objectives The pharmacokinetics and pharmacodynamics of tolvaptan (7.5 or 15 mg/day) in combination with furosemide have been investigated in heart failure (HF) patients with normal kidney function but not in HF patients with advanced kidney dysfunction. This study evaluated the efficacy of tolvaptan in HF patients with advanced kidney dysfunction (estimated glomerular filtration rate 2) by conducting a pharmacokinetic and pharmacodynamic study in these patients. Methods Tolvaptan (15 mg once daily) was administered orally for 7 days in combination with furosemide (40-200 mg). Results The peak plasma tolvaptan concentration and area under the plasma concentration-time curve were 379.41 ± 149.69 ng/mL and 4,657.38 ± 2,741.79 ng·h/mL, respectively, in HF patients with advanced kidney dysfunction. These values were greater in HF patients with advanced kidney dysfunction than values reported in the literature for healthy subjects and HF patients with normal kidney function. Urine volume increased and body weight decreased significantly compared with those before tolvaptan administration in HF patients with advanced kidney dysfunction. Conclusion This study showed that adding tolvaptan to furosemide was effective in HF patients with advanced kidney dysfunction. This study also suggests that in these patients 15 mg/day of tolvaptan should be sufficient, and increasing the dose or the frequency of dosing to overcome diuretic resistance should not be necessary, and consideration should be given to using a lower dose and/or prolonging the dosing interval.
    Clinical Pharmacokinetics 10/2014; 54(3). DOI:10.1007/s40262-014-0194-6 · 5.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acute kidney injury complicates decompensated heart failure in ∼33% of cases and is associated with morbidity and mortality, thus, we sought to systematically review this topic in order to summarize novel diagnostic and therapeutic approaches.Methods Structured PubMed searches on these topics were conducted in February 2014 and relevant literature was identified. The PubMed search identified a total of 192 articles that were individually screened for inclusion in this analysis and 58 were included.ResultsAcute kidney injury, defined by substantial rises in serum creatinine, is consistently associated with prolonged length of stay, rehospitalization, and mortality. Biomarker studies suggested that natriuretic peptides are prognostic for shorter and longer term mortality. Novel proteins indicating kidney damage and albumin in the urine are associated with acute kidney injury. The most promising acute pharmacologic treatment appears to be serelaxin, which has been shown to improve acute heart failure symptoms, hemodynamic parameters, and renal function.Conclusions The presence of acute kidney injury results in worse clinical outcomes for patients with acute heart failure. Novel biomarkers and therapies hold the promise of improving both cardiac and renal outcomes in these patients.
    The American Journal of Medicine 11/2014; 128(3). DOI:10.1016/j.amjmed.2014.10.035 · 5.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acute decompensated heart failure (ADHF) is the most common cause of cardiovascular hospitalization. The presentation is characterized by different clinical profiles due to various underlying causes, volume balance and tissue perfusion status. Currently, a variety of pharmacological therapies, including diuretics, beta-blockers, ACE-inhibitors, angiotensin receptor blockers and digoxin, are usually prescribed in order to treat chronic heart failure (HF) syndromes caused by left ventricular systolic dysfunction. Despite the large number of HF patients with frequent hospitalizations for decompensation, only a few studies have evaluated the management of oral chronic therapies in the clinical setting of ADHF. This article summarizes the information derived from the few published trials on this subject and a therapeutic approach is suggested with respect to the continuation, dose modification or suspension of oral medications.
    International Journal of Cardiology 08/2014; 176(2). DOI:10.1016/j.ijcard.2014.07.085 · 6.18 Impact Factor