Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group.

Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality.

A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators.

BACKGROUND: Vesnarinone, an inotropic drug, was shown in a short-term placebo-controlled trial to improve survival markedly in patients with severe heart failure when given at a dose of 60 mg per day, but there was a trend toward an adverse effect on survival when the dose was 120 mg per day. In a longer-term study, we evaluated the effects of daily doses of 60 mg or 30 mg of vesnarinone, as compared with placebo, on mortality and morbidity. METHODS: We enrolled 3833 patients who had symptoms of New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 30 percent or less despite optimal treatment. The mean follow-up was 286 days. RESULTS: There were significantly fewer deaths in the placebo group (242 deaths, or 18.9 percent) than in the 60-mg vesnarinone group (292 deaths, or 22.9 percent) and longer survival (P=0.02). The increase in mortality with vesnarinone was attributed to an increase in sudden death, presumed to be due to arrhythmia. The quality of life had improved significantly more in the 60-mg vesnarinone group than in the placebo group at 8 weeks (P<0.001) and 16 weeks (P=0.003) after randomization. Trends in mortality and in measures of the quality of life in the 30-mg vesnarinone group were similar to those in the 60-mg group but not significantly different from those in the placebo group. Agranulocytosis occurred in 1.2 percent of the patients given 60 mg of vesnarinone per day and 0.2 percent of those given 30 mg of vesnarinone. CONCLUSIONS: Vesnarinone is associated with a dose-dependent increase in mortality among patients with severe heart failure, an increase that is probably related to an increase in deaths due to arrhythmia. A short-term benefit in terms of the quality of life raises issues about the appropriate therapeutic goal in treating heart failure.

Efficacy of esmolol in the treatment and transfer of patients with supraventricular tachyarrhythmias to alternate oral antiarrhythmic agents.

The efficacy and safety of esmolol, a titratable intravenous beta-adrenergic blocking agent with a short elimination half-life (t 1/2 = 9.0 min) was evaluated in a multicenter open-label study for the treatment of supraventricular tachyarrhythmias (heart rate greater than 100 bpm). The study also investigated the feasibility of transferring patients from esmolol to alternate oral antiarrhythmic agents without loss of therapeutic response. Of the 113 patients studied, 95 (84%) achieved therapeutic response (reduction in heart rate of 15% or more or conversion to sinus rhythm). Most of these patients (93%) achieved the therapeutic response at esmolol doses of 200 micrograms/kg/min or lower. Transfer from esmolol to an oral antiarrhythmic agent(s) was studied in 76 patients. Alternate antiarrhythmic agents used in this study were digoxin (N = 25), propranolol (N = 21), verapamil (N = 10), metoprolol (N = 11), quinidine (N = 2), and a combination of two antiarrhythmic agents (N = 7). Sixty-seven (88%) patients were successfully transferred to oral antiarrhythmic agents without loss of the therapeutic response obtained with esmolol. The most frequent adverse effect observed during the study was hypotension, which resolved quickly (16 +/- 14 min) either by decreasing the dose or by discontinuation of esmolol infusion. This study supports previous observations concerning the safety and efficacy of esmolol in the treatment of supraventricular tachyarrhythmias. Furthermore, it demonstrates that the majority of patients successfully treated with esmolol can be safely and effectively transferred to oral therapy with alternate antiarrhythmic agents.

Efficacy of nifedipine gastrointestinal therapeutic system in combination with beta blockers in the management of exertional angina. A multicenter study of 54 patients.

This multicenter study assessed the efficacy of a new formulation of nifedipine in 54 patients with stable angina pectoris receiving beta-blocker therapy. This once-daily preparation of nifedipine was administered in double-blind fashion in doses of 30, 60, and 90 mg. All patients experienced pain-limited exercise at placebo baseline treadmill testing. Eight hours post-dose exercise testing resulted in a significant increase in time to onset of angina for all three dose levels of nifedipine but not for placebo. Exercise testing 24 hours after dosing showed significant improvement in time to angina and total exercise time for patients receiving 60-mg and 90-mg doses but not for the 30-mg or placebo categories. These preliminary results suggest that this new formulation of nifedipine is beneficial when added to stable doses of a beta blocker in patients in whom angina is still exhibited during exercise testing.