Data are limited regarding the long-term efficacy of tolvaptan in adults aged 18-35 years with autosomal dominant polycystic kidney disease (ADPKD) at increased risk of rapid progression. We assessed the effects of tolvaptan within a larger population of younger adults and over longer follow-up than individual clinical trials could provide. Pooled database study. A consolidated clinical study database with ADPKD patients aged 18-35 years. Studies that enrolled patients who received either tolvaptan or standard-of-care treatment not including tolvaptan. Annual rate of change in estimated glomerular filtration rate (eGFR) and time to kidney failure. For individuals participating in multiple studies, their data were longitudinally linked to extend the follow-up period. We matched tolvaptan-treated patients with controls based on age, sex, chronic kidney disease stage, eGFR, and, where possible, Mayo Imaging Classification. We compared eGFR decline between groups using mixed-effects modeling. The matched analysis set encompassed 204 tolvaptan-treated individuals and 204 controls. Median follow-up was 4.6 years for the tolvaptan group and 1.7 years for controls. In the mixed-effects model, the eGFR decline rate (in mL/min/1.73 m2/year) was -2.58 for the tolvaptan cohort and -4.28 for controls. This indicates reduction in the eGFR decline rate by 1.69 mL/min/1.73 m2/year (95% confidence interval: 0.87-2.52; P < 0.001) with tolvaptan, a 40% improvement. Extrapolating eGFR over 35 years, tolvaptan could delay kidney failure onset by approximately 11 years. Median follow-up was shorter in the control cohort than the tolvaptan cohort. The projection of time to kidney failure assumed a linear model of eGFR decline. This analysis offers insights into the anticipated treatment benefits of tolvaptan for young adults with ADPKD. These findings are crucial for weighing treatment benefits against any associated risks.
Abstract Background Low‐density lipoprotein cholesterol (LDL‐C) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited real‐world data on LDL‐C lowering with evolocumab in United States clinical practice. Hypothesis We assessed LDL‐C lowering during 1 year of evolocumab therapy. Methods This retrospective cohort study used linked laboratory (Prognos) and medical claims (IQVIA Dx/LRx and PharMetrics Plus ® ) data. Patients with a first fill for evolocumab between 7/1/2015 and 10/31/2019 (index event) and LDL‐C ≥ 70 mg/dL were included (overall cohort; N = 5897). Additionally, a patient subgroup with a recent myocardial infarction (MI) within 12 months (median 130 days) before the first evolocumab fill was identified (N = 152). Reduction from baseline LDL‐C was calculated based on the lowest LDL‐C value recorded during a 12‐month follow‐up period. Results The mean (SD) age was 65 (10) years; 61.9% of patients had ASCVD diagnoses and 70.7% of patients were in receipt of lipid‐lowering therapy. Following evolocumab treatment, changes in LDL‐C from baseline were −60% in the overall cohort (median [interquartile range (IQR)] 146 [115–180] mg/dL to 58 [36–84] mg/dL) and −65% in the recent MI subgroup (median [IQR] 137 [109–165] mg/dL to 48 [30–78] mg/dL). In the overall cohort and recent MI subgroup, 62.1% and 69.7% of patients achieved LDL‐C < 70 mg/dL, respectively. Conclusions In this real‐world analysis, evolocumab was associated with significant reductions in LDL‐C comparable to that seen in the FOURIER clinical trial, which were durable over 1 year of treatment.
