ABSTRACT
BACKGROUND: Assessing haemodynamic congestion based on filling pressures instead of clinical congestion can be a way to further improve quality of life (QoL) and clinical outcome by intervening before symptoms or weight gain occur in heart failure (HF) patients. The clinical efficacy of remote monitoring of pulmonary artery (PA) pressures (CardioMEMS; Abbott Inc., Atlanta, GA, USA) has been demonstrated in the USA. Currently, the PA sensor is not reimbursed in the European Union as its benefit when applied in addition to standard HF care is unknown in Western European countries, including the Netherlands. AIMS: To demonstrate the efficacy and cost-effectiveness of haemodynamic PA monitoring in addition to contemporary standard HF care in a high-quality Western European health care system. METHODS: The current study is a prospective, multi-centre, randomised clinical trial in 340 patients with chronic HF (New York Heart Association functional class III) randomised to HF care including remote monitoring with the CardioMEMS PA sensor or standard HF care alone. Eligible patients have at least one hospitalisation for HF in 12 months before enrolment and will be randomised in a 1:1 ratio. Minimum follow-up will be 1 year. The primary endpoint is the change in QoL as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Secondary endpoints are the number of HF hospital admissions and changes in health status assessed by EQ-5D-5L questionnaire including health care utilisation and formal cost-effectiveness analysis. CONCLUSION: The MONITOR HF trial will evaluate the efficacy and cost-effectiveness of haemodynamic monitoring by CardioMEMS in addition to standard HF care in patients with chronic HF. Clinical Trial Registration number NTR7672.
ABSTRACT
BACKGROUND: Chronic heart failure (CHF) is a potential indication for the administration of EMD 87 580, a selective Na+/H+ exchange inhibitor. CHF is often accompanied by renal dysfunction, which is known to affect the pharmacokinetics of compounds predominately cleared by the kidneys. We examined the influence of renal dysfunction on the pharmacokinetics of EMD 87 580 in patients with CHF. METHODS: 21 patients with CHF and normal renal function (Group 1) and 9 patients with CHF and renal dysfunction (Group 2) received EMD 87 580 orally over 8 days. The mean creatinine clearance (CrCl) in Group 1 was 99.7 ml/min. 12 patients in this group were randomized to receive two doses of EMD 87 580 (7 patients 2 x 50 mg and 5 patients 2 x 100 mg). The 9 patients in Group 2 with renal dysfunction (mean CrCl = 49.5 ml/min) received 50 mg EMD 87 580 once daily. Plasma and urine samples were collected for pharmacokinetic assessment. RESULTS: In CHF patients with renal dysfunction EMD 87 580 clearance was reduced to approximately 50% compared to Group 1, i.e. 6.80 ml/min (4.89-11.60) vs. 12.73 ml/min (8.93-22.21), p < 0.05, for the 50 mg dose and 14.08 ml/min (9.96-18.10), p < 0.05, for the 100 mg dose. Consequently, plasma concentrations were increased in patients with renal dysfunction; AUC0-infinity 7,354 ng/ml x h (4,311-10,232) vs. 3,928 ng/ml x h (2,251-5,596, 50 mg dose, p < 0.05). A significant correlation was observed between EMD 87 580 plasma clearance and CrCl (r2 = 0.8062). CONCLUSION: In CHF patients with renal dysfunction EMD 87 580, clearance is reduced and plasma concentrations increased. Therefore, dose adjustments for EMD 87 580 are indicated in patients with CHF and renal dysfunction.