Contemporary Trends in the Management and Outcomes of Patients With Familial Hypercholesterolemia in Canada: A Prospective Observational Study.

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is one of the most common genetic diseases in the world and an important cause of premature cardiovascular (CV) disease. The purpose of this study was to characterize the clinical features, current treatment patterns, and CV outcomes of patients with HeFH in British Columbia, Canada. METHODS: We conducted a longitudinal observational study of patients with HeFH attending a specialized lipid clinic. We collected data on lipid levels, medication use, and CV events at baseline and last follow-up. RESULTS: We recruited 339 patients with clinically diagnosed HeFH, with a total of 3700 person-years of follow-up. The mean low-density lipoprotein cholesterol (LDL-C) level was 5.9 mmol/L at baseline and 3.7 mmol/L at last follow-up. Use of lipid-lowering therapy (LLT) increased from 35.7% at baseline to 84.7% at last follow-up. A ≥ 50% reduction in LDL-C level was achieved in 34.5% of patients, and an LDL-C level ≤ 2 mmol/L was seen in 8.3%. The overall CV event rate in this cohort was 33.5/1000 person-years. Among patients who had a CV event during follow-up, 59% experienced a recurrent event within 5 years. CONCLUSIONS: These data contribute to our understanding of contemporary trends in the management of patients with HeFH in Canada. Despite a majority of patients receiving LLT, few patients reached high-risk lipid targets. These data highlight important opportunities to improve the care of patients with HeFH.

Efficacy, quality of life, and safety of cabazitaxel in Canadian metastatic castration-resistant prostate cancer patients treated or not with prior abiraterone.

INTRODUCTION: In the TROPIC study, cabazitaxel improved overall survival in abiraterone-naïve metastatic castration-resistant prostate cancer (mCRPC) patients post-docetaxel. To evaluate cabazitaxel in routine clinical practice, an international, single-arm trial was conducted. Efficacy, safety, and quality of life (QoL) data were collected from Canadian patients enrolled. Overall survival and progression-free survival were not collected as part of this study. Importantly, prior abiraterone use was obtained and its impact on clinical parameters was examined. METHODS: Sixty-one patients from nine Canadian centres were enrolled, with prior abiraterone use known for 60 patients. Prostate-specific antigen (PSA) response rate, safety, and impact on QoL life were analyzed as a function of prior abiraterone use. RESULTS: Overall, 92% of patients were ECOG 0/1, 88% had bone metastases, and 25% visceral metastases. Patients treated without prior abiraterone (NoPriorAbi) (n=35, 58%) and with prior abiraterone (PriorAbi) (n=25, 42%) had similar baseline characteristics, except for age and prior cumulative docetaxel dose. Median number of cabazitaxel cycles received was similar between groups (NoPriorAbi=6, PriorAbi=7), as was PSA response rate (NoPriorAbi=36.4%, PriorAbi=45.0%, p=0.54). Almost one-third (31%) of patients received prophylactic granulocyte colony-stimulating factors. Most frequent Grade 3/4 toxicities were neutropenia (14.8%); anemia, febrile neutropenia, fatigue (each at 9.8%); and diarrhea (8.2%). No treatment-related adverse event leading to death was observed. QoL and pain were improved with no difference seen between groups. Treatment discontinuation was mainly due to disease progression (45.9%) and adverse events (32.8%). CONCLUSIONS: In routine clinical practice, cabazitaxel's risk-benefit ratio in mCRPC patients previously treated with docetaxel seems to be maintained independent of prior abiraterone use.

Meta-analysis and economic evaluation of LH-RH agonists' depot formulations in advanced prostatic carcinoma.

The present study compares the relative efficacy, safety and cost of therapy of the following LH-RH agonists: buserelin acetate (Suprefact(R) Depot, Hoechst Marion Roussel), goserelin acetate (Zoladex(R) LA, Zeneca Pharma Inc.), and leuprolide acetate (Lupron(R) SR Depot, Abbott Laboratories Inc.). To support the conduct of a cost-minimization analysis in patients with advanced prostatic carcinoma their comparable efficacy and safety was first assessed using a meta-analysis technique. The absence of statistically significant differences among the 2 major end points, survival and progression-free survival was confirmed. The cost-minimization analysis for the depot formulations was conducted from the perspectives of the provincial formulary and the Ministry of Health, and considered 2 time horizons: 1 year, and mean survival time of 2.5 years. Cost differences among LH-RH agonists were sensitive to changes in dosing interval and patient survival time but, even when these parameters were varied, for a general population of patients with advanced prostate cancer, buserelin remained the most cost-saving treatment alternative among LH-RH agonists.