Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies.

AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors consistently reduce low-density lipoprotein cholesterol (LDL-C) by 50-60% and lipoprotein(a) (Lp(a)) by 20-30%, but the mechanism of Lp(a) lowering remains unclear. If Lp(a) is cleared by the LDL receptor, similar to LDL-C, then one would expect PCSK9 inhibition to induce a concordant LDL-C/Lp(a) response in an approximately 2:1 ratio. We aim to determine the prevalence of discordant plasma LDL-C/Lp(a) response to the PCSK9 inhibitor alirocumab. METHODS: This is a post hoc, pooled analysis of 10 randomized controlled trials from the ODYSSEY Phase 3 clinical trial program for alirocumab. Patients enrolled in the trials were high cardiovascular risk and/or with heterozygous familial hypercholesterolemia. The primary end point was prevalence of discordant LDL-C/Lp(a) response to alirocumab at 24 weeks. Discordant response was defined as LDL-C reduction >35% and Lp(a) reduction ≤10%, or LDL-C reduction ≤35% and Lp(a) reduction >10%. RESULTS: Of the 1709 patients in the pooled study cohort, 62.4% were male, and the mean age was 59.2 (SD: 11.0) years. Baseline mean LDL-C was 126.5 (SD: 46.3) mg/dL and baseline median Lp(a) was 46.9 (interquartile range: 21.8-89.0) mg/dL. Total prevalence of discordant LDL-C/Lp(a) response was 21.5% (12.6% with LDL-C >35% reduction and Lp(a) ≤10% reduction; 8.9% with LDL-C ≤35% reduction and Lp(a) >10% reduction). Baseline Lp(a) and familial hypercholesterolemia status did not affect discordance. CONCLUSION: A high prevalence of discordant LDL-C/Lp(a) response was observed with alirocumab, further suggesting that PCSK9 inhibitor therapy with alirocumab reduces plasma Lp(a) through alternative pathways to LDL receptor clearance.

Statin utilization and low-density lipoprotein cholesterol in statin-treated patients with atherosclerotic cardiovascular disease: Trends from a community-based health care delivery system, 2002-2016.

BACKGROUND: A better understanding of patterns in statin utilization and low-density lipoprotein cholesterol (LDL-C) among patients with atherosclerotic cardiovascular disease (ASCVD) in a clinical practice setting is needed. OBJECTIVES: The objective of this study was to examine statin utilization and LDL-C among new statin users with ASCVD. METHODS: This retrospective study used an electronic health record database from a community-based health care system. We identified ASCVD patients ≥21 years of age with a new statin prescription during the study period (2002-2016). Outcomes included high-intensity statin therapy (HIST) prescribing at treatment initiation, medication adherence (defined as proportion of days covered ≥0.80), statin therapy titrations rates, and changes in LDL-C during follow-up. RESULTS: Among 6199 eligible patients, mean follow-up was 16.8 months. At treatment initiation, 16.6% of patients received HIST. Approximately 53% of patients were adherent to statin regimens. Mean percent reduction in LDL-c was 25% during follow-up; 18% of patients, overall, and 30% of those initiating on HIST attained LDL-C reductions >50%. Rates of statin intensity-level increases were 8.4 per 100 person-years. HIST prescribing increased over time, beginning after generic atorvastatin availability and preceded treatment guidelines by two years. Initiation on HIST, higher adherence, and treatment intensification during follow-up were independent predictors of attaining LDL-C goals of <70 mg/dL or <100 mg/dL. CONCLUSIONS: In a community-based health care system, modest LDL-C lowering for secondary ASCVD prevention is likely driven by suboptimal adherence and low HIST prescribing and treatment intensification rates. Clinician and patient education are needed to reduce clinical inertia and improve medication adherence to better manage ASCVD.

Dietary supplement use among menopausal women attending a San Francisco health conference.

OBJECTIVE: This study examined the usage patterns of dietary supplements during menopause, providing information about type, prevalence, and rationale for use. METHODS: A survey instrument was distributed to self-identified peri- or postmenopausal women at a San Francisco women's health conference in March 2000. RESULTS: Of the 100 eligible women, 29% used hormone replacement therapy (HRT) alone, 16% used HRT with dietary supplements (Combo group), 32% used dietary supplements alone, and 13% used no product or used supplements excluded in this survey. The most common dietary supplements were soy (29%), ginkgo biloba (16%), and black cohosh (10%). Only 54% of women using dietary supplements reported such usage to their primary care providers. Women using HRT alone reported relief of hot flashes significantly more often than those using dietary supplements alone (63% vs. 30%; p = 0.016). Women using combination therapy reported enhanced improvement in vaginal dryness, libido, and mood compared with those using HRT alone. Perceived quality of life and overall control of menopausal symptoms were highest among women using dietary supplements alone and women using combination therapy, respectively. Satisfaction with menopausal counseling from a primary care provider was significantly greater in women receiving HRT alone ( p = 0.02) and combination therapy ( p = 0.006) compared with women receiving dietary supplements alone. CONCLUSIONS: Dietary supplements were frequently used during menopause. Combined use of dietary supplements and HRT seemed to be associated with enhanced relief of certain menopausal symptoms. Women using dietary supplements alone seemed particularly dissatisfied with the menopausal counseling provided by a primary care provider.