Poor adherence with hypolipidemic drugs: a lost opportunity

All articles assessing adherence to hypolipidemic drugs were reviewed and categorized by patient population (clinical trial, unselected) and reported as rates of nonadherence and discontinuation. Overall, levels of discontinuation reported in clinical trials (6-31%) and lipid clinics (2-38%) are similar, with unselected populations consistently reporting higher rates (15-78%). Rates of nonadherence in clinical trials and lipid clinics also are comparable, with unselected populations having the highest rates. Across all settings, rates of discontinuation and nonadherence are consistently reported to be poorer with resins and niacin than with hydroxy-6-methylglutamate coenzyme A reductase inhibitors. Adherence to hypolipidemic agents appears to decrease in parallel with level of follow-up. Data evaluating mechanisms of poor adherence are limited. While the search for new, efficacious therapies must continue, efforts focused on improving adherence to proven therapy may have a greater overall impact on health than any single new agent.     

Examining factors associated with adherence to hormonal therapy in breast cancer patients

BackgroudBreast cancer is a rampant disease and is highly prevalent among women in the United States. Two out of three breast cancers are hormone receptor positive and hormonal therapies (Tamoxifen and Aromatase Inhibitors) are used to treat this type of breast cancer. However, adherence to these efficacious therapies is relatively low.PurposeThe aim of this study was to identify factors that are associated with adherence to hormonal therapy among breast cancer patients, and the extent to which they influence adherence, by looking at data from a nationally representative database.MethodsA retrospective cross-sectional study was conducted using Medical Expenditure Panel Survey (MEPS) for 2011–2015. Individuals ≥18 years diagnosed with breast cancer utilizing Tamoxifen and Aromatase inhibitors were identified. The Proportion of Days Covered (PDC) adherence measure was used to classify individuals as adherent (PDC≥80%) or non-adherent (PDC<80%). Multivariable logistic regression was used to determine factors associated with adherence to hormonal therapy.ResultsOut of the 354 breast cancer respondents utilizing hormonal therapy, 194 (54.8%) were adherent and 160 (45.20%) were non-adherent. From 2011 through 2015, an increase in the usage of hormonal therapy was observed. Individuals having at least a high school diploma or General Equivalency Diploma (GED) had 2.795 (1.081, 6.941) times the odds of being adherent when compared to those who did not have a high school diploma or GED. Race, insurance status, marital status, poverty level, class of drug (aromatase inhibitor/tamoxifen), age, comorbidities, out-of-pocket costs and region were not significantly associated with adherence to hormonal therapy among breast cancer patients.ConclusionsThis study found an association between an individual's level of education and adherence to hormonal therapy among breast cancer patients. These results can be used to help optimize allocation of resources to promote knowledge designed to increase the adherence of breast cancer patients to hormonal therapy.     

The role of lipid-lowering drugs in cognitive function: a meta-analysis of observational studies

STUDY OBJECTIVE: To quantify the risk of cognitive impairment with use of lipid-lowering drugs. DESIGN AND DATA SOURCES: Literature search through MEDLINE and EMBASE databases; data from seven observational studies were analyzed. MEASUREMENTS AND MAIN RESULTS: We quantified the risk of cognitive impairment first with the use of any lipid-lowering drug, and then specifically with the statins, using the random effects model. We tested for heterogeneity using the Q statistic as well as quantitatively using the Ri statistic. All seven studies provided data for statin users, and five provided data only on use of lipid-lowering drugs. Compared with patients not receiving lipid-lowering drugs, the relative risk of cognitive impairment with any lipid-lowering drug was 0.62 but was not statistically significant (95% confidence interval [CI] 0.28-1.38), and the relative risk with statins was 0.43 and was statistically significant (95% CI 0.31-0.62). CONCLUSION: Lipid-lowering drugs--in particular, the statins--seem to lower the odds of developing cognitive impairment. Randomized, controlled trials are needed to address the efficacy of these agents specifically in different types of dementia.     

Safety and tolerability of injectable lipid-lowering drugs: a review of available clinical data

Introduction: To answer the need of a better low-density lipoprotein (LDL) cholesterol control in statin-treated patients at high risk for cardiovascular disease, new injectable lipid-lowering drugs with innovative mechanisms of action are in advanced phase of development or have just been approved.

Areas covered: Evolocumab and alirocumab are fully human monoclonal antibodies inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) that binds to hepatic LDL receptor and prevents it from normal recycling by targeting it for degradation. Mipomersen specifically binds to a segment of the human apolipoprotein B100 messenger RNA, blocking the translation of the gene product. Phase II (for evolocumab and alirocumab) and III (for evolocumab) trials show that PCSK9 inhibitors are equally well tolerated, with adverse events mainly limited to mild-to-moderate nasopharyngitis, injection-site pain, arthralgia and back pain. Mipomersen use is mainly associated to hepatosteatosis, increased transaminases (> 3 times the upper limit of normal), mild-to-moderate injection-site reactions and flu-like symptoms.

Expert opinion: PCSK9 inhibitors have demonstrated their good safety and tolerability in a large number of subjects with different clinical conditions, including statin-intolerance, enlarging their potential use in a broader range of patients. Further data on long-term mipomersen safety are required.     

Patient factors associated with adherence to immunosuppressant therapy in renal transplant recipients.

PURPOSE: Factors associated with adherence to immunosuppressant therapy (IST) in renal transplant recipients were studied. METHODS: The Immunosuppressant Therapy Adherence Scale (ITAS) was completed by adult renal transplant recipients in Georgia. Those completing the ITAS were classified as adherent to IST if their ITAS score were 12 and nonadherent if their score was less than 12. The relationship between the dichotomized ITAS scores and patient variables that are readily available to clinicians, such as sex, age, kidney donor type, income, marital status, race or ethnicity, and time since transplantation, was assessed. The relationship of ITAS scores to patients' clinical and pharmacy data (e.g., graft rejection, serum IST concentrations, serum creatinine [SCr] concentrations, and pharmacy refill-based adherence rates) was also assessed. RESULTS: One hundred thirty-seven patients completed the ITAS. Eighty-nine patients (65%) were adherent to IST, and the remaining 48 (35%) were nonadherent. Patient sex was unrelated to adherence. Compared with nonadherent patients, adherent patients tended to be younger, to take cyclosporine, to have lower incomes, to have received their transplant more recently, to have targeted immunosuppressant concentrations, to have greater refill-based adherence rates, and to be less likely to exhibit an increase in SCr concentration (p < 0.05). There was no significant difference in the number of rejections between adherent and nonadherent patients. CONCLUSION: Patient age, income, time since transplantation, and the immunosuppressant agent prescribed were associated with IST adherence.     

Rurality and other factors associated with adherence to immunosuppressant medications in community-dwelling solid-organ transplant recipients

BackgroundData on immunosuppressant adherence of community-dwelling adult solid-organ transplant recipients (SOTRs) from rural populations in the United States are limited. Therefore, understanding the association of rurality and other factors of immunosuppressant adherence will help providers design and deliver patient-centered adherence enhancing interventions.ObjectivesThe objective was to examine factors associated with a previously validated 4-item Immunosuppressant Therapy Adherence Scale (ITAS) score in community-dwelling adult SOTRs who received a transplant from an academic center in the Midwestern United States.MethodsFor this observational study, cross-sectional survey data (patient demographic, medical condition, immunosuppressant therapy, and self-reported ITAS) received from adult SOTRs aged 19 years or older with other data from an academic transplant center’s database were merged. Using multivariate logistic regression, significant SOTR characteristics associated with being adherent (ITAS score = 12) versus nonadherent (ITAS score <12) were examined.ResultsThe survey response rate was 30% (n = 556/1827). Those SOTRs responding (n = 556) had a kidney (48%), liver (47%), or other (4.5%) transplant. They were more likely to be 50- to 64-year olds (52%), men (55%), white (90%), metroresident (59%), with an annual income less than $55,000. The SOTRs were living with a transplant for 6.3 years (median), reported excellent-to-good health status (77%), and received different immunosuppressant regimens. More than half of the SOTRs (58%) were adherent. In multivariate analyses, compared with patients aged 65 years or older, younger patients, nonmetro rural- versus metroresident, and those having more (≥6) versus less (<6) comorbidities were significantly less likely to report adherence. SOTRs receiving tacrolimus-based combination immunosuppressant versus tacrolimus alone were more likely to report adherence.ConclusionsWhen designing and delivering patient care-centered interventions including those that use technology to increase immunosuppressant adherence, providers need to consider rural residence besides other well-established patient factors (younger age, immunosuppressant drug, and comorbidities) of nonadherence.     

Global systematic review and ecological analysis of HIV in people who inject drugs: National population sizes and factors associated with HIV prevalence

BackgroundPeople who inject drugs (PWID) are at elevated risk of HIV infection. Data on population sizes of PWID living with HIV are needed to inform the implementation of prevention, treatment and care programs. We estimated national population sizes of people who recently (past 12 months) injected drugs living with HIV and evaluated ecological associations with HIV prevalence in PWID.MethodsWe used national data on the prevalence of injecting drug use and of HIV among PWID, derived from systematic reviews, to estimate national population sizes of PWID living with HIV. Uncertainty was estimated using Monte Carlo simulation with 100,000 draws. We extracted data on sample characteristics from studies of HIV prevalence among PWID, and identified national indicators that have been observed or hypothesised to be associated with HIV prevalence in PWID. We used linear regression to evaluate associations between these variables and HIV prevalence in PWID.ResultsFour countries comprised 55% of the estimated global population of PWID living with HIV: Russia (572,500; 95% uncertainty interval (UI) 235,500–1,036,500); Brazil (462,000; 95% UI 283,500–674,500); China (316,500; 95% UI 171,500–493,500), and the United States (195,500; 95% UI 80,000–343,000). Greater anti-HCV prevalence and national income inequality were associated with greater HIV prevalence in PWID.ConclusionThe countries with the largest populations of PWID living with HIV will need to dramatically scale up prevention, treatment and care interventions to prevent further increases in population size. The association between anti-HCV prevalence and HIV prevalence among PWID corroborates findings that settings with increasing HCV should implement effective interventions to prevent HIV outbreaks. The association between income inequality and HIV among PWID reinforces the need to implement structural interventions alongside targeted individual-level strategies.     

Apolipoprotein E genotypes are associated with lipid-lowering responses to statin treatment in diabetes: a Go-DARTS study

BACKGROUND: Apolipoprotein E (APOE) genotypes have been associated with variations in plasma-lipid levels and with response to statins, although the influence of APOE on the response to statins remains controversial, especially in patients with diabetes. We sought to evaluate the association of the APOE genotype with the low-density lipoprotein cholesterol (LDLc)-lowering response to statins, in a large population-based cohort of patients with diabetes. METHODS AND RESULTS: A total of 1383 patients, commencing statins between 1990 and 2006, were identified from the Genetics of Diabetes Audit and Research in Tayside Scotland database. Statin response was determined both by the minimum LDLc achieved, and by the failure of the patients to reach a clinical target LDLc (< or =2 mmol/l). APOE genotype and potential confounding covariates were entered into the linear and logistic regression models. RESULTS: We found an association of APOE genotypes with both baseline and treatment responses. E2 homozygotes achieved lower LDLc levels (mean 0.6; confidence interval: 0.1-1.1 mmol/l) than E4 homozygotes (mean 1.7; confidence interval: 1.4-1.9 mmol/l; P=2.96 x 10). Minimum LDLc was associated by a linear trend with genotype. This relationship remained statistically significant after adjustment for baseline LDLc, adherence, duration, dose, smoking, and age. None of the E2 homozygotes failed to reach the target LDLc, compared with 32% of the E4 homozygotes (P=5.3 x 10). CONCLUSION: This study demonstrates the potential clinical value of the APOE genotype as a robust marker for LDLc responses to statin drugs, which might contribute to the identification of a particularly drug-resistant subgroup of patients. This marker provides information over and above baseline lipid levels.     

Organisational factors associated with safety climate,patient satisfaction and self-reported medicines adherence in community pharmacies

BackgroundEvidence suggests that community pharmacy service quality varies, and that this may relate to pharmacy ownership. However little is known about wider organisational factors associated with quality.ObjectiveTo investigate organisational factors associated with variation in safety climate, patient satisfaction and self-reported medicines adherence in English community pharmacies.MethodsMultivariable regressions were conducted using data from two cross-sectional surveys, of 817 pharmacies and 2124 patients visiting 39 responding pharmacies, across 9 diverse geographical areas. Outcomes measured were safety climate, patient satisfaction and self-reported medicines adherence. Independent variables included service volume (e.g. dispensing volume), pharmacy characteristics (e.g. pharmacy ownership), patient characteristics (e.g. age) and areal-specific demographic, socio-economic and health-needs variables.ResultsValid response rates were 277/800 (34.6%) and 971/2097 (46.5%) for pharmacy and patient surveys respectively. Safety climate was associated with pharmacy ownership (F_8,225 = 4.36, P < 0.001), organisational culture (F_{4, 225} = 12.44, P < 0.001), pharmacists' working hours (F_{4, 225} = 2.68, P = 0.032) and employment of accuracy checkers (F_{4, 225} = 4.55, P = 0.002). Patients’ satisfaction with visit was associated with employment of pharmacy technicians (β = 0.0998, 95%CI = [0.0070,0.1926]), continuity of advice-giver (β = 0.2593, 95%CI = [0.1251,0.3935]) and having more reasons for choosing that pharmacy (β = 0.3943, 95%CI = [0.2644, 0.5242]). Satisfaction with information received was associated with continuity of advice-giver (OR = 1.96, 95%CI = [1.36, 2.82]), weaker belief in medicines overuse (OR = 0.92, 95%CI = [0.88, 0.96]) and age (OR = 1.02, 95%CI = [1.01, 1.03]). Regular deployment of locums by pharmacies was associated with poorer medicines adherence (OR = 0.50, 95%CI = [0.30, 0.84]), as was stronger patient belief in medicines overuse (OR = 0.88, 95%CI=[0.81, 0.95]) and younger age (OR = 1.04, 95%CI = [1.01, 1.07]). No patient outcomes were associated with pharmacy ownership or service volume.ConclusionsThis study characterised variation in the quality of English community pharmacy services identifying the importance of skill-mix, continuity of care, pharmacy ownership, organisational culture, and patient characteristics. Further research is needed into what constitutes and influences quality, including the development of validated quality measures.     

Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data

Introduction: Cardiovascular (CV) diseases are the leading cause of death and disability in the developed countries. Lipid-lowering therapy is a cornerstone of the CV risk modification strategy. The first line treatment for hyperlipidemia is statins, which decrease low-density lipoprotein cholesterol (LDL-C) by 30–50% and proportionally reduce the CV events. However, they are not always enough to achieve LDL-C goals in many patients, and some patients are statin intolerant. For this reason, new powerful injectable lipid-lowering drugs have been developed.

Areas covered: The aim of this narrative review was to summarize the more recent clinical data on safety and tolerability of injectable lipid-lowering drugs. After an attentive literature search, the authors resumed here information on proprotein convertase subtilisin/kexin 9 inhibitors (evolocumab and alirocumab), small interfering RNA molecule inclisiran, antisense oligonucleotides (mipomersen, volanesorsen, ISIS 681257), and drugs targeting angiopoietin-like protein 3 (evinacumab, IONIS-ANGPTL3_Rx).

Expert opinion: Injectable lipid-lowering therapy for patients at high risk for CV disease complications or with severe inherited hypercholesterolemias can be an important element of the available therapeutic armamentarium. Clinical data prove the favorable risk-benefit profile of evolocumab, alirocumab, and inclisiran. Mipomersen, volanesorsen, ISIS 681257, evinacumab, and IONIS-ANGPTL3_Rx safety is currently less extensively studied, especially in patients with comorbidities and polypharmacotherapy.