Richard Ofori-Asenso

Adherence and Persistence among Statin Users Aged 65 Years and Over: A Systematic Review and Meta-analysis

BackgroundnOlder people (aged ≥ 65 years) have distinctive challenges with medication adherence. However, adherence and persistence patterns among older statin users have not been comprehensively reviewed.nnnMethodsnAs part of a broader systematic review, we searched Medline, Embase, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects, CENTRAL, and the National Health Service Economic Evaluation Database through December 2016 for English articles reporting adherence and/or persistence among older statin users. Data were analyzed via descriptive methods and meta-analysis using random-effect modeling.nnnResultsnData from more than 3 million older statin users in 82 studies conducted in over 40 countries were analyzed. At 1-year follow-up, 59.7% (primary prevention 47.9%; secondary prevention 62.3%) of users were adherent (medication possession ratio [MPR] or proportion of days covered [PDC] ≥ 80%). For both primary and secondary prevention subjects, 1-year adherence was worse among individuals aged more than 75 years than those aged 65-75 years. At 3 and ≥10 years, 55.3% and 28.4% of users were adherent, respectively. The proportion of users persistent at 1-year was 76.7% (primary prevention 76.0%; secondary prevention 82.6%). Additionally, 68.1% and 61.2% of users were persistent at 2 and 4 years, respectively. Among new statin users, 48.2% were nonadherent and 23.9% discontinued within the first year. The proportion of statin users who were adherent based on self-report was 85.5%.nnnConclusionsnThere is poor short and long term adherence and persistence among older statin users. Strategies to improve adherence and reduce discontinuation are needed if the intended cardiovascular benefits of statin treatment are to be realized.

A Systematic Review and Meta-analysis of the Factors Associated With Nonadherence and Discontinuation of Statins Among People Aged ≥65 Years

BackgroundnOlder individuals (aged ≥65 years) are commonly prescribed statins but may experience a range of barriers in adhering to therapy. The factors associated with poor statin adherence and/or discontinuation among this population have not been comprehensively reviewed.nnnMethodsnWe conducted a systematic review to identify English articles published through December 12, 2016 that reported factors associated with nonadherence and/or discontinuation of statins among older persons. Data were pooled via random-effects meta-analysis techniques.nnnResultsnForty-five articles reporting data from more than 1.8 million older statin users from 13 countries were included. The factors associated with increased statin nonadherence were black/non-white race (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.39-1.98), female gender (OR 1.08, 95% CI 1.03-1.13), current smoker (OR 1.12, 95% CI 1.03-1.21), higher copayments (OR 1.38, 95% CI 1.25-1.52), new user (OR 1.58, 95% CI 1.21-2.07), lower number of concurrent cardiovascular medications (OR 1.08, 95% CI 1.06-1.09), primary prevention (OR 1.49, 95% CI 1.40-1.59), having respiratory disorders (OR 1.17, 95% CI 1.12-1.23) or depression (OR 1.11, 95% CI 1.06-1.16), and not having renal disease (OR 1.09, 95% CI 1.04-1.14). The factors associated with increased statin discontinuation were lower income status (OR 1.20, 95% CI 1.06-1.36), current smoker (OR 1.14, 95% CI 1.06-1.23), higher copayment (OR 1.61, 95% CI 1.53-1.70), higher number of medications (OR 1.04, 95% CI 1.01-1.06), presence of dementia (OR 1.18, 95% CI 1.02-1.36), cancer (OR 1.22, 95% CI 1.11-1.33) or respiratory disorders (OR 1.19, 95% CI 1.05-1.34), primary prevention (OR 1.66, 95% CI 1.24-2.22), and not having hypertension (OR 1.13, 95% CI 1.07-1.20) or diabetes (OR 1.09, 95% CI 1.04-1.15).nnnConclusionnInterventions that target potentially modifiable factors including financial and social barriers, patients perceptions about disease risk as well as polypharmacy may improve statin use in the older population.

Patterns and Predictors of Adherence to Statin Therapy Among Older Patients: Protocol for a Systematic Review

Background The benefits of statin therapy are significantly compromised by noncompliance. Although elderly patients may have particular challenges with medication adherence and persistence, previous reviews on statin adherence have not focused on this population. Additionally, comparisons of adherence and persistence specific to statin indication (primary or secondary prevention) have not been thoroughly explored. Objective We aim to assess the extent of, and factors associated with, adherence and persistence to statin therapy among older populations (aged ≥65 years). Methods A systematic review will be undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Searches will be performed using multiple electronic databases (Ovid MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and the National Health Service Economic Evaluation Database) to identify relevant randomized trials and observational studies that evaluated statin adherence and/or persistence as an outcome. Eligible studies will include those involving community-living or outpatient elderly individuals. The methodological quality of randomized controlled trials (RCTs) will be assessed via the Joanna Briggs Institute’s critical appraisal checklist for RCTs, and the quality assessment of observational studies will be undertaken using a set of questions formulated with resort to the National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. When possible, meta-analyses will be conducted using random-effect modeling and generic inverse variance analyses for adjusted-effect estimates. Heterogeneity across studies will be quantified using the I2 statistic. The presence of publication bias will be assessed using funnel plots and Egger’s regression tests. A leave-one-out sensitivity analysis will also be conducted to assess the impact of individual study results on pooled estimates. To explore possible sources of heterogeneity across studies, subgroup analyses will be performed based on covariates such as study design, statin indication, country of study, and length of patient follow-up. Results The electronic database searches were completed in December 2016. Retrieved articles are currently being screened and the entire study is expected to be completed by June 2017. Conclusions This systematic review will provide further understanding of the patterns of, and barriers to, statin adherence and persistence among older patients. The findings will inform clinical practice and the design of appropriate interventions. Trial Registration PROSPERO CRD42016053191

Patterns of statin use and long-term adherence and persistence among older adults with diabetes: 老年糖尿病患者使用他汀类药物的模式以及长期依从性与持久性

Statins reduce the risk of cardiovascular disease in patients with diabetes. This study examined the prevalence of statin use and assessed long‐term adherence and persistence among people aged ≥65u2009years with diabetes.

LDL‐Cholesterol Is the Only Clinically Relevant Biomarker for Atherosclerotic Cardiovascular Disease (ASCVD) Risk

Recent years have witnessed the emergence of promising novel lipid and nonlipid biomarkers for atherosclerotic cardiovascular disease (ASCVD), with suggestions that some of these may be superior to lowdensity lipoprotein cholesterol (LDL-C). In the present viewpoint, we compare LDL-C and other biomarkers against the three key criteria for the clinical utility of a biomarker: accuracy, reliability, and therapeutic relevance. We conclude that the available data support LDL-C as the most clinically relevant biomarker for ASCVD risk. Despite declining mortality, ASCVD remains the most common cause of morbidity and mortality worldwide. Furthermore, the burden of disease is projected to rise due to population aging and an increasing prevalence of risk factors, notably in developing countries. Optimal primary and secondary prevention of ASCVD is dependent on accurate estimation of the risk of future incident or recurrent ASCVD using demographic, clinical, and biomarker information. Despite the title of this article, we do not support the premise that LDL-C is the “only clinically relevant biomarker for ASCVD” risk. Cardiovascular risk is the consequence of the complex interplay of multiple genetic and somatic factors and its evaluation should consider multiple cardiovascular biomarkers, including indicators of glycemic control, hemostasis, myocardial damage and inflammation, as well as other risk factors including smoking, hypertension, obesity, and physical inactivity. Rather, in the present viewpoint we argue that LDL-C is the “most clinically relevant biomarker for ASCVD risk.” LDL-C has been the primary biomarker for ASCVD risk prediction and goaldirected therapy for decades. However, recent years have witnessed the emergence of many novel biomarkers, including those outside of lipid metabolic pathways, and there remains skepticism of the “LDL hypothesis.” To support our argument, we will first summarize data for LDL-C drawn from laboratory studies, prospective cohort studies, genetic epidemiology, and randomized controlled trials, assessing these against the three key criteria for the clinical utility of a biomarker: 1) accuracy (able to identify persons at risk); 2) reliability (able to be measured consistently); and 3) therapeutic relevance (able to help guide therapy). Then we will evaluate the currently most promising other lipid, and novel, biomarkers against the same criteria.

Reinitiation of Statin Therapy After Discontinuation: A Meta-analysis

CVD, its relationship to the CAC score is less clear. For example, endurance athletes with high fitness have been reported to have greater CAC scores than ageand risk factorematched controls. Moreover, a recent study reported decreased mortality in highly fit individuals with increased CAC scores. Such paradoxical findings suggest that the association between CAC score and fitness is more complex than previously believed. These conflicting data may be partially attributed to differing methodologies employed for fitness assessment and the quantitation of CAC. Most previous studies regarding these associations have relied primarily on Agatston scores, rather than advanced CAC volume and density scores. Accordingly, we sought to determine whether high fitness, directly measured by expired gas analysis as an objective index of fitness, expressed as VO2peak, correlated with varied CAC scoring indices. Although the CAC volume score is positively associated with CVD risk, it appears that CAC density is inversely related to the risk of incident cardiovascular events. Elevated CAC density scores may suggest plaque stabilization; thus, greater CAC density may be associated with more stable coronary disease and a reduced likelihood of plaque rupture. Accordingly, the Agatston score alone may be inadequate to predict CVD risk, given the inverse relationship between CAC density and CVD risk. In the present study, higher fitness was inversely related to advanced CAC by Agatston and volume scores but directly related to advanced CAC density, suggesting that fitness may be associated with CAC plaque morphology. Collectively, these data suggest that high fitness may attenuate coronary calcification and increase plaque stabilization, potentially reducing the risk of cardiovascular events in men.

Predictors of Statin Use among Older Adults: A Nationwide Cross-Sectional Study

BACKGROUNDnStatins comprise a key strategy for the prevention and treatment of arteriosclerotic cardiovascular disease, but prescribing remains suboptimal.nnnOBJECTIVESnThe objective of this study was to characterize the predictors of statin use among adults aged ≥65xa0years.nnnMETHODSnA cross-sectional study using Pharmaceutical Benefits Scheme (PBS) data on reimbursed prescriptions for a 10% random sample of the Australian population in 2016 was performed. Predictors of statin use were identified via multivariable logistic regression. Analyses were performed separately for people who were concessional beneficiaries (with a low, capped copayment) and other (general) people.nnnRESULTSnAmong 351,471 (concessionalxa0=xa0295,875 and generalxa0=xa055,596) older adults, 44.2% were dispensed statins (concessionalxa0=xa046.4% and generalxa0=xa032.2%). Among the concessional beneficiaries, people aged 75 to 84xa0years were more likely to use statins (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.06-1.10), whereas those aged ≥85xa0years were less likely to use statins (OR 0.71, 95% CI 0.69-0.72), compared with people aged 65 to 74xa0years. Men were more likely to use statins than women (OR 1.14, 95% CI 1.12-1.16). Diabetes was associated with over 2-fold (OR 2.48, 95% CI 2.43-2.53) increased likelihood of statin use. People with cardiovascular-related conditions including hypertension, angina, and congestive heart failure experienced increased likelihood of statin use as was being dispensed anticoagulant or antiplatelet medication. Having malignancy, psychotic illness, or pain were associated with lower likelihood of statin use. Similar predictors of statin use were noted for the general population.nnnCONCLUSIONnMore than 40% of older adults in Australia used statins in 2016 with uptake dependent on individual-level factors such as demographics and comorbidities. Future research should examine the extent to which provider and/or health system-level factors contribute to the variable uptake of statin therapy.

A 10-Year Trend in Statin Use Among Older Adults in Australia: an Analysis Using National Pharmacy Claims Data

BackgroundStatins have become standard of care in the prevention and treatment of atherosclerotic cardiovascular disease. The objective of this study was to examine the trends in statin use among Australians aged ≥u200965xa0years for the period 2007–2016.MethodsData from the Pharmaceutical Benefits Scheme covering a 10% random sample of the Australian population were analysed. The 1-year prevalence and incidence of statin use were determined for each year, as were the percentage of statin dispensations according to statin type or intensity and the percentage of new users prescribed each statin type or intensity. To describe relative changes, age-sex adjusted rate ratios (RRs) and 95% confidence intervals (CIs) were determined via Poisson regression modelling using 2007 as the reference year.ResultsThe 1-year prevalence of statin use increased consistently each year from 34.2% in 2007 to 44.1% in 2016 (RR 1.29, 95% CI 1.28–1.31). The 1-year incidence was 68.5 per 1000 in 2007 and 59.0 per 1000 in 2016 (RR 0.87, 95% CI 0.84–0.90). Women were 18% (age-adjusted rate ratio [aRR] 0.82, 95% CI 0.79–0.83) less likely than men to initiate statins across all years. The incidence of statin use was also highest among individuals aged 65–74xa0years, who were about 15% (sex-adjusted rate ratio [sRR] 1.15, 95% CI 1.13–1.16) and 45% (sRR 1.45, 95% CI 1.44–1.47) more likely to initiate statins than those aged 75–84 and ≥xa085 years, respectively. Atorvastatin was the most commonly dispensed statin across all years. The proportion of new users dispensed high-intensity statins increased year-on-year from 23.6% in 2007 to 30.5% in 2016 (RR 1.26, 95% CI 1.21–1.31).ConclusionThe proportion of older adults in Australia using statins has increased over the last decade, although the incidence has declined. Atorvastatin is the most commonly dispensed statin and the use of high intensity statin has increased.

Prevalence and Incidence of Statin Use and 3-Year Adherence and Discontinuation Rates Among Older Adults With Dementia

Objective: To examine the patterns of statin use and determine the 3-year adherence and discontinuation rates among a cohort of Australians aged ≥65 years with dementia. Methods: The yearly prevalence and incidence of statin use were compared via Poisson regression modeling using 2007 as the reference year. People with dementia were identified according to dispensing of antidementia medications. A cohort of 589 new statin users was followed longitudinally. Adherence was estimated via the proportion of days covered (PDC). Discontinuation was defined as ≥90 days without statin coverage. Results: The annual prevalence of statin use among older Australians with dementia increased from 20.6% in 2007 to 31.7% in 2016 (aged-sex adjusted rate ratio: 1.51, 95% confidence interval: 1.35-1.69). Among the new users, the proportion adherent (PDC ≥ 0.80) decreased from 60.3% at 6 months to 31.0% at 3 years. During the 3-year follow-up, 58.7% discontinued their statin. Conclusions: Despite increased use of statins among older Australians with dementia, adherence is low and discontinuation is high, which may point to intentional cessation.