Effects of multiple oral doses of an A1 adenosine antagonist, BG9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study.

OBJECTIVES: This study sought to assess the pharmacokinetics and clinical effects of oral BG9928 in heart failure (HF) patients. BACKGROUND: Declining renal function during HF treatment is associated with poor outcomes. BG9928, a selective inhibitor of the A1 adenosine receptor, is proposed to cause natriuresis without causing a decline in renal function. METHODS: A randomized, double-blind, placebo-controlled study was conducted in patients with HF and systolic dysfunction who were receiving standard therapy. Patients were randomized to receive BG9928 (3, 15, 75, or 225 mg) or placebo orally for 10 days. The primary end point was change in sodium excretion. Changes in potassium excretion, creatinine clearance, and body weight also were evaluated. RESULTS: A total of 50 patients were studied. BG9928 increased sodium excretion compared with placebo, and natriuresis was maintained over 10 days with little kaliuresis. A linear trend in dose response was observed on day 1 (p = 0.04) but not on days 6 or 10. Adjusted creatinine clearance was unchanged over the 10 days. Patients who received 15, 75, or 225 mg of BG9928 had a reduction in body weight compared with placebo (-0.6, -0.7, -0.5, vs. +0.3 kg, respectively) at the end of study. BG9928 was well tolerated. The pharmacokinetic profile of BG9928 was consistent with once-daily dosing. CONCLUSIONS: Oral BG9928 over the dose range of 3 to 225 mg/day produced significant increases in sodium excretion in patients with stable HF without causing kaliuresis or reducing renal function.

Automatic sensor algorithms expedite pacemaker follow-ups.

OBJECTIVE: Automatic algorithms can be used to optimize settings and reduce the duration of pacemaker (PM) clinical follow-up. METHODS: This study prospectively evaluated 87 patients (74.2 +/- 10.7 years old, 52% men) who received PM with the Autoslope algorithm. Patients randomized to the manual group (group M, n = 43) performed a walk test and used sensor-indicated rate histograms to adjust the sensor, while in the automatic group (group A, n = 44) the sensor was automatically adjusted by the Autoslope. The patients were followed for 6 months. Follow-up time required for device interrogation and optimal sensor set-up, and the number of sensor parameters reprogramming were recorded. Changes in the patients' activity level were also evaluated. RESULTS: Group A required significantly less follow-up time than group M (9.4 +/- 5.7 min vs 13.5 +/- 8.5 min, P = 0.0002). The average number of sensor parameters reprogrammed during visits was significantly lower in group A than M (0.6 +/- 0.9 vs 0.9 +/- 1.3, P = 0.048). Threshold was adjusted 34.4% of the time in the sensor evaluations in group M versus 12.9% in group A (P = 0.0004). Although more patients in group A reported being more active, the changes in patients' activity level did not lead to increasing sensor setup time or number of parameter reprogramming in either group. CONCLUSIONS: Auto sensor adjustment required less time during routine PM clinical follow-up by reducing steps needed for manual sensor threshold adjustment.