RESUMO
BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronisation therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life, clinical, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were nonsignificant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = 0.03; adjusted Pinteraction = 0.33) and diabetics (Pinteraction = 0.01; adjusted Pinteraction = 0.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.
RESUMO
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.
