Real-World Outcomes of Proprotein Convertase Subtilisin Kexin-9 Inhibitor Use.

ABSTRACT: Although the proprotein convertase subtilisin kexin-9 inhibitors (PCSK9i) were shown to significantly lower low-density lipoprotein and reduce atherosclerotic cardiovascular disease events in clinical trials, there is a dearth of use data on these agents in real-world settings. This study compares PCSK9i use in a population of real-world patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia. This was a matched cohort study of adult patients who were dispensed a PCSK9i along with adult patients who did not receive a PCSK9i. PCSK9i patients were matched on a propensity to have received a PCSK9i score up to 1:10 to non-PCSK9i patients. The primary outcomes were changes in cholesterol levels. Secondary outcomes included a composite outcome of all-cause mortality, major cardiovascular events, and ischemic strokes along with health care utilization during follow-up. Adjusted conditional, multivariate Cox proportional hazards, and negative binomial modeling were performed. Ninety-one PCSK9i patients were matched to 840 non-PCSK9i patients. Seventy-one percent of PCSK9i patients either discontinued or switched PCSK9i therapy. PCSK9i patients had greater median reductions in low-density lipoprotein (-73.0 mg/dL vs. -30.0 mg/dL) and total (-77.0 vs. -31.0) cholesterol (both P < 0.001). No adjusted between-group differences in the composite outcome or individual components of the composite outcome were identified (all P > 0.05). PCSK9i patients had a lower rate of medical office visits during follow-up (adjusted incidence rate ratio = 0.61, P = 0.019). These findings support the effectiveness of PCSK9i therapy in real-world settings but suggest that use may be limited by PCSK9i adverse reactions and patient cost barriers.

Flat-dose granulocyte colony-stimulating factor evaluation after autologous hematopoietic stem cell transplant in multiple myeloma patients: Does one dose fit all?

INTRODUCTION: The current recommended granulocyte-colony stimulating factor (G-CSF) dose after autologous hematopoietic stem cell transplant (autoHSCT) in multiple myeloma patients is 5 mcg/kg/day administered subcutaneously until engraftment. Recently, our institution changed practice from weight-based to flat-dose G-CSF. The purpose of this study was to assess the impact of flat-dose G-CSF on time to engraftment among multiple myeloma patients of different weight groups. METHODS: Retrospective chart review was completed for adult patients with multiple myeloma who underwent autoHSCT from March 2018 through August 2019. Data collected included time to neutrophil engraftment, total length of hospitalization, length of stay post-transplant, time to platelet engraftment, use of intravenous fluconazole or acyclovir, parenteral nutrition use, incidence of febrile neutropenia, antibiotic use, and death. Differences in outcomes were compared between patients ≤80 kg versus those >80 kg. A secondary analysis was completed for patients ≤100 kg versus those >100 kg. RESULTS: There was no difference in time to neutrophil engraftment between weight groups (≤80 kg versus >80 kg: median = 12 days, p = 0.22; ≤100 kg versus >100 kg: median = 12 days, p = 0.52). There was a significant difference in intravenous fluconazole and acyclovir use between groups, with more use in the lower weight groups (≤80 kg versus >80 kg: 12 patients versus 10 patients p = 0.02; ≤100 kg versus >100 kg: 19 patients versus 3 patients p = 0.04). No significant differences were found for any other outcomes. CONCLUSION: Utilizing a flat-dose of G-CSF for patients after autoHSCT does not appear to negatively affect patient outcomes. Institutions may benefit from using the 300 mcg dose of G-CSF for multiple myeloma patients after autoHSCT.