Sacubitril/valsartan in peritoneal dialysis patients
Hypertension and heart failure are particular problems for many patients on peritoneal dialysis (PD). Both associate with an increased risk of all-cause and cardiovascular mortality.
Sacubitril/valsartan (SV) is a familiar treatment for patients with chronic HF and is known to have significant effects on blood pressure. This single, open-label and cross-sectional study, conducted in China, set out to explore the pharmacokinetics and pharmacodynamics of SV in patients with PD complicated by hypertension or HF, about which little was known.
For the study, 40 patients who had received PD for over one month, and had a diagnosis of hypertension and/or HF (New York Heart Association class 2–4), were enrolled. Participants were assigned to one of three treatment groups: 50 mg SV twice daily, 100 mg once daily or 100 mg twice daily.
Concentrations of valsartan, sacubitril and sacubitrilat (LBQ657, the active metabolite of sacubitril) were measured in plasma, urine and peritoneal dialysate samples. Pharmacodynamic assessment was carried out by comparing changes in mean sitting systolic blood pressure (msSBP), mean sitting diastolic pressure (msDBP), mean sitting heart rate (msHR), NT-proBNP and left ventricular ejection fraction (LVEF).
In the highest dosage 100 mg twice-daily group, the maximum drug concentrations were 1995±1499 ng/mL for valsartan, 171±148 ng/mL for sacubitril and 13,686±7418 ng/mL for LBQ657. The 24-hour recovery rate of the active metabolite LBQ657 was 3.77% in urine and 2.23% in peritoneal dialysate, indicating that PD and residual renal function could only marginally remove it.
There were significant reductions from baseline after SV use in msSBP (19.25±10.32 mmHg), msDBP (10.10±8.00 mmHg) and msHR (3.00 beats/min). NT-proBNP decreased by 1436.50 ng/L from baseline, while LVEF increased by 5.00%.
No SV-related adverse reactions were reported, and the authors concluded that a dosage of 100 mg twice daily is likely to be safe in patients with PD complicated by hypertension or HF, but owing to limitations of size and the lack of a control group, this study should act as a starting point for further confirmatory studies and for precision medicine of SV in PD patients.
The full study can be read here.
