Efficacy and safety of a modified dosage regimen of nesiritide in patients older than 75 years with acute heart failure.
ABSTRACT Background and Aims: To explore efficacy and safety of a modified dosage regimen of nesiritide in patients (≥75 years) with acute heart failure (AHF). Methods: Total 140 patients (≥75 years) with AHF were enrolled in this study. They were randomly and evenly divided into two group- control and nesiritide group. The control group received only conventional treatment for AHF, while the nesiritide group received conventional treatment plus a continual intravenous infusion of nesiritide at a rate of 0.0075～0.015 µg•kg-1•min-1 for 10-15 hours (total 0.5-1.0 mg) once daily for 13 days. Results: Medical research council scales in nesiritide group were significantly lower than those in control group on day 4, 8 and 14. Scores of edema had no significant difference, but were lower in nesiritide group on day 8 and 14. The nesiritide group had markedly more net body fluid losses. NT-proBNP, serum creatinine, blood pressure, cTnI, 30-day and 60-day mortality had no significant difference between two groups. Conclusions: Nesiritide resulted in improvements in dyspnea and edema, and similar adverse effects compared with conventional treatment. In spite of no reduction on short-term mortality and a reversible influence on renal function, nesiritide was still an important chioce for the elderly (≥75 years) with AHF.
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ABSTRACT: Acute decompensated heart failure (ADHF) represents the most common discharge diagnosis in patients over age 65, and has an exceptionally high mortality and read-mission risk. ADHF is characterized by abnormal hemodynamics, including increase in pulmonary capillary wedge pressure and peripheral vasoconstriction, although cardiac index may be reduced, normal, or increased. Myocardial injury, which may be related to decreased coronary perfusion, activation of neurohormones, and/or renal dysfunction, may contribute to short-term and postdischarge cardiovascular events. Recent ADHF registries have provided valuable insights into the characteristics, treatment patterns, and clinical outcomes of these patients. Most patients with ADHF present with either normal systolic blood pressure or elevated blood pressures; hypotension is relatively uncommon. These patients have significant cardiovascular and noncardiovascular comorbidities that may contribute to the pathogenesis and/or adverse outcomes in ADHF. Therapies for ADHF have been targeted to improve symptoms and hemodynamics, as well as preserve or improve renal function, prevent myocardial damage, modulate neurohumoral and inflammatory activation, and manage other comorbidities that may cause and/or contribute to the progression of this syndrome. Concomitant therapies proven to provide long-term benefits in chronic heart failure are also essential. There remains an unmet need for therapeutic approaches for the early management of ADHF that may improve short- and long-term outcomes. Ongoing clinical trials are intended to provide data that will better define the benefits and risks of therapies for ADHF.Reviews in cardiovascular medicine 02/2007; 8 Suppl 5:S3-12. · 1.18 Impact Factor
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ABSTRACT: Renal function is an important prognostic factor for patients with acutely decompensated heart failure (ADHF). We investigated the renal effects of nesiritide as treatment for ADHF. Randomized clinical trials comparing nesiritide with either placebo or active control for ADHF were identified by electronic and manual searches and thorough review of US Food and Drug Administration files available via the website. Worsening renal function was defined as an increase in serum creatinine >0.5 mg/dL. Relative risk across all studies was determined by meta-analysis with Mantel-Haenszel fixed-effects models (RR(MH)). Risk of dialysis and medical intervention for worsening renal function were compared between therapies. Frequency of worsening renal function was determined from 5 randomized studies that included 1269 patients. Use of Food and Drug Administration-approved doses of nesiritide (< or =0.03 microg x kg(-1) x min(-1)) significantly increased the risk of worsening renal function compared with non-inotrope-based control (RR(MH), 1.52; 95% CI, 1.16 to 2.00; P=0.003) or any control therapy, including non-inotrope- and inotrope-based therapies (RR(MH), 1.54; 95% CI, 1.19 to 1.98; P=0.001). Even low-dose nesiritide (< or =0.015 microg x kg(-1) x min(-1)) significantly increased risk (P=0.012 and P=0.006 compared with non-inotrope- and inotrope-based controls, respectively), as did nesiritide administered at any dose up to 0.06 microg x kg(-1) x min(-1) (P=0.002 and P=0.001, respectively). There was no difference in the need for dialysis between therapies. Nesiritide significantly increases the risk of worsening renal function in patients with ADHF. Whether worsening renal function reflects hemodynamic effect or renal injury is unknown, but the prognostic importance of worsening renal function suggests the need for further investigation in appropriately powered clinical trials.Circulation 03/2005; 111(12):1487-91. · 14.95 Impact Factor
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ABSTRACT: Nesiritide improves symptoms in patients with acutely decompensated heart failure compared with placebo and appears to be safer than dobutamine. Its short-term safety relative to standard diuretic and vasodilator therapies is less clear. To investigate the safety of nesiritide relative to noninotrope-based control therapies, primarily consisting of diuretics or vasodilators. Primary reports of completed clinical trials as of December 2004 were obtained from the US Food and Drug Administration (FDA), the study sponsor (Scios Inc), a PubMed literature search using the terms nesiritide, clinical trials, and humans, and a manual search of annual meetings of 3 heart associations. Of 12 randomized controlled trials evaluating nesiritide, 3 met all inclusion criteria: randomized double-blind study of patients with acutely decompensated heart failure, therapy administered as single infusion (> or =6 hours), inotrope not mandated as control, and reported 30-day mortality. Data were extracted from FDA and sponsor documents and corroborated with published articles when available. Thirty-day survival was assessed by meta-analysis using a fixed-effects model and time-dependent risk by Kaplan-Meier analysis with Cox proportional hazards regression modeling. Where deaths were described within a range of days after treatment, an extreme assumption was made favoring nesiritide over control therapy, an approach relevant to the time-dependent analyses. In the 3 trials, 485 patients were randomized to nesiritide and 377 to control therapy. Death within 30 days tended to occur more often among patients randomized to nesiritide therapy (35 [7.2%] of 485 vs 15 [4.0%] of 377 patients; risk ratio from meta-analysis, 1.74; 95% confidence interval [CI], 0.97-3.12; P = .059; and hazard ratio after adjusting for study, 1.80; 95% CI, 0.98-3.31; P = .057). Compared with noninotrope-based control therapy, nesiritide may be associated with an increased risk of death after treatment for acutely decompensated heart failure. The possibility of an increased risk of death should be investigated in a large-scale, adequately powered, controlled trial before routine use of nesiritide for acutely decompensated heart failure.JAMA The Journal of the American Medical Association 04/2005; 293(15):1900-5. · 29.98 Impact Factor