Statin Adherence Research Articles

Significant Facility-Level Variation in Utilization of and Adherence with Secondary Prevention Therapies Among Patients with Premature Atherosclerotic Cardiovascular Disease: Insights from the VITAL (Veterans wIth premaTure AtheroscLerosis) Registry7

We investigated facility-level variation in the use and adherence with antiplatelets and statins among patients with premature and extremely premature ASCVD. Using the 2014-2015 nationwide Veterans wIth premaTure AtheroscLerosis (VITAL) registry, we assessed patients with premature (age at first ASCVD event: males < 55years, females < 65years) and extremely premature ASCVD (< 40years). We examined frequency and facility-level variation in any statin, high-intensity statin (HIS), antiplatelet use (aspirin, clopidogrel, ticagrelor, prasugrel, and ticlopidine), and statin adherence (proportion of days covered ≥ 0.8) across 130 nationwide VA healthcare facilities. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of statins or antiplatelets and statin adherence. Our analysis included 135,703 and 7716 patients with premature and extremely premature ASCVD, respectively. Across all facilities, the median (IQR) prescription rate of any statin therapy, HIS therapy, and antiplatelets among patients with premature ASCVD was 0.73 (0.70-0.75), 0.36 (0.32-0.41), and 0.77 (0.73-0.81), respectively. MRR (95% CI) for any statin use, HIS use, and antiplatelet use were 1.53 (1.44-1.60), 1.58 (1.49-1.66), and 1.49 (1.42-1.56), respectively, showing 53, 58, and 49% facility-level variation. The median (IQR) facility-level rate of statin adherence was 0.58 (0.55-0.62) and MRR for statin adherence was 1.13 (1.10-1.15), showing 13% facility-level variation. Similar median facility-level rates and variation were observed among patients with extremely premature ASCVD. There is suboptimal use and significant facility-level variation in the use of statin and antiplatelet therapy among patients with premature and extremely premature ASCVD. Interventions are needed to optimize care and minimize variation among young ASCVD patients.

Assessing the association between medication adherence, as defined in quality measures, and disease-state control, health care utilization, and costs in a retrospective database analysis of Medicare supplemental beneficiaries using statin medications.

BACKGROUND: Adherence to medication, and related health and economic outcomes, is becoming increasingly important as populations age and as the number of Americans managing chronic conditions increases. The Pharmacy Quality Alliance (PQA) statin medication adherence measure is used in Medicare star ratings to evaluate health plan performance. Yet, limited evidence exists that investigates the association between statin medication adherence, as specified in the PQA adherence quality measure, and disease-state control, health care utilization, and costs. OBJECTIVE: To determine the association between adherence (≥80% proportion of days covered) and disease-state control, health care utilization, and health care costs for Medicare supplemental beneficiaries using statin medications eligible for inclusion in the PQA statin adherence quality measure. METHODS: This retrospective study used a cohort of eligible beneficiaries for inclusion in the PQA statin adherence measure with low-density lipoprotein (LDL) laboratory values from IBM MarketScan Medicare Supplemental Research Databases (2009-2015). A logistic regression model assessed the association between adherence and LDL control (controlled individuals had LDL levels ≤ 100 mg/dL). Health care utilization and costs during a 1-year period, from first statin medication claim, were compared between adherent and nonadherent groups using generalized linear models with log link and negative binomial distribution (utilization) or gamma distribution (costs), adjusting for covariates. Beta coefficients were used to compute cost ratios (CR) and rate ratios (RR). Cohort characteristics were assessed using t-tests, Wilcoxon rank sum tests, or chi-square tests. An a priori alpha level of 0.001 was used. RESULTS: The study cohort consisted of 77,174 beneficiaries, of whom 58,668 (76.0%) were classified as adherent to their statin medications. After controlling for other factors, odds of disease-state control were approximately 2 times higher among medication adherent beneficiaries compared with their nonadherent counterparts (OR = 2.192; 95% CI = 2.109-2.278). Multivariable analyses showed adherers experienced 4.7% fewer outpatient (RR = 0.953; 95% CI = 0.940-0.965) and 27.5% fewer inpatient (RR = 0.725; 95% CI = 0.687-0.766) visits; had 9.9% lower outpatient (CR = 0.901; 95% CI = 0.885-0.916) and 28.3% lower inpatient (CR = 0.717; 95% CI = 0.705-0.729) costs; 14.7% lower total costs (CR = 0.853; 95% CI =0.838-0.868); and 7.0% higher prescription drug costs (CR = 1.070; 95% CI = 1.052-1.089) than nonadherers. Adherence to statin medications was associated with a reduction in total costs of $157.32 per member per month. CONCLUSIONS: This retrospective database analysis demonstrated that statin adherence was associated with approximately twice the odds of having a controlled disease state compared with nonadherence in a large Medicare sample. Adherent beneficiaries had fewer outpatient and inpatient visits (lower utilization), lower outpatient and inpatient costs, and lower total costs, a calculated savings of $157.32 per member per month, despite having higher prescription drug costs. Finally, these results provide important new information by demonstrating that adherence (≥ 80%) is associated with lower health care costs in a short (1-year) time frame. DISCLOSURES: Funding for this study was provided by Pharmacy Quality Alliance; Merck & Co. (Kenilworth, NJ); and SinfoniaRx. All authors except Pickering and Black were employed by the University of Arizona College of Pharmacy or the Mel & Enid Zuckerman College of Public Health at the time of this study. Pickering is employed by the Pharmacy Quality Alliance, and Black is employed by Merck & Co. Chinthammit also reports employment with Eli Lilly and Company, and Campbell reports employment with the Pharmacy Quality Alliance. Axon reports grants from Arizona Department of Health Services, unrelated to this work. Warholak reports grants from Novartis and the Arizona Department of Health Services, unrelated to this work. This research was presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Annual Meeting 2019, May 18-22, 2019, in New Orleans, LA.

Age, race/ethnicity, and comorbidities predict statin adherence after ischemic stroke or myocardial infarction.

Age, race/ethnicity, and comorbidities predict statin adherence after ischemic stroke or myocardial infarction.

Statin treatment reduces the risk of death among elderly frail patients: evidence from a large population-based cohort.

To assess the protective effect of statins in a large and unselected cohort of frail elderly subjects. The 460460 Lombardy residents (Italy), aged ≥65 years, who received ≥3 consecutive prescriptions of a statin during 2011-2012 were identified. A case-control study was performed, the cases being the cohort members who died during 2011-2018. Logistic regression was used to model the outcome risk associated with statin adherence. Adherence to drug therapy was measured by the proportion of the follow-up covered by prescriptions. The analysis was stratified according to four clinical categories (good, medium, poor, and very poor clinical status), based on different life expectancies, as assessed by a prognostic score which had been found to sensitively predict the risk of death. The 7-year death probability increased from 11% (good) to 52% (very poor clinical status). In each clinical status, there was a significant reduction of all-cause mortality as adherence to statin treatment increased. The reduction in the adjusted risk of mortality from the lowest to the highest adherence level was greatest among patients with a good clinical status (-56%) and progressively less among other cohort members, i.e. -48%, -44% and -47% in medium, poor, and very poor groups, respectively. Similar findings were obtained for the risk of cardiovascular mortality. In a real-life setting, adherence to statin treatment reduced the death risk also in frail elderly patients. However, in these patients, the benefit of statin treatment may be lower than in those in good clinical conditions.

Assessment of Trends in Statin Therapy for Secondary Prevention of Atherosclerotic Cardiovascular Disease in US Adults From 2007 to 2016

Atherosclerotic cardiovascular disease (ASCVD) is highly prevalent in the US, with studies indicating substantial rates of nonadherence to and undertreatment with statin therapy. The 2013 American College of Cardiology/American Heart Association guideline recommended high-intensity statins for all patients age 75 years and younger with documented ASCVD in whom such therapy is tolerated, but there is limited evidence documenting population trends of statin use, adherence, and outcomes in the periods before and after the update to the guideline. To assess trends in the use, adherence, cost, and outcomes of statin therapy for secondary prevention in patients with different types of ASCVD between 2007 and 2016. This retrospective cohort study used data from the OptumLab Data Warehouse database containing privately insured and Medicare Advantage enrollees with demographic characteristics similar to the national US population. Participants were adult patients (age ≥21 years) who had their first ASCVD event between January 1, 2007, and December 31, 2016. Data were characterized as belonging to 3 groups: (1) cardiovascular heart disease (CHD); (2) ischemic stroke or transient ischemic attack (TIA); and (3) peripheral artery disease (PAD). Data were analyzed from July 1 to August 1, 2018. Calendar year of the initial ASCVD event. Trends in the statin use (within 30 days of discharge from hospitalization), adherence (proportion of days covered ≥80% within the first year), cost, major adverse cardiac events (1-year cumulative risk), and statin intolerance (within the first year). Of the 284 954 patients with a new ASCVD event, 128 422 (45.1%) were women; the median age was 63 years (interquartile range [IQR], 54-72 years); 207 781 (72.9%) were White. The use of statins increased from 50.3% in 2007 to 59.9% in 2016, the use of high-intensity statins increased from 25.0% to 49.2%, and the adherence increased from 58.7% to 70.5% (P < .001 for all trends). Patients with CHD were more likely to receive statins and high-intensity statins and adhere to medications than patients with ischemic stroke, TIA, or PAD despite similar observed treatment benefit. In 2016, 80.9% of patients with CHD used a statin vs 65.8% of patients with ischemic stroke or TIA and 37.5% of patients with PAD. Out-of-pocket cost per 30-day decreased from a median of $20 (interquartile range, $7.6-$31.9) in 2007 to $2 (interquartile range, $1.6-$10.0) in 2016 (P < .001) with the increasing use of generic statins (42.0% in 2007 vs 94.9% in 2016; P < .001). Major adverse cardiac events decreased from 8.9% in 2007 to 6.5% in 2016 (P < .001) whereas statin intolerance increased from 4.0% to 5.1% (P < .001). There have been modest improvements in the use, adherence, and cardiovascular outcomes over the past decade for statin therapy in patients with ASCVD, but a substantial and persistent treatment gap exists between patients with and without CHD, between men and women.

Statin adherence is lower in primary than secondary prevention: A national follow-up study of new users.

Maintaining adherence to statins reduces the risk of an initial cardiovascular disease (CVD) event in high-risk individuals (primary prevention) and additional CVD events following the first event (secondary prevention). The effectiveness of statin therapy is limited by the level of adherence maintained by the patient. We undertook a nationwide study to compare adherence and discontinuation in primary and secondary prevention patients. Dispensing data from New Zealand community pharmacies were used to identify patients who received their first statin dispensing between 2006 and 2011. The Medication Possession Ratio (MPR) and proportion who discontinued statin medication was calculated for the year following first statin dispensing for patients with a minimum of two dispensings. Adherence was defined as an MPR ≥ 0.8. Previous CVD was identified using hospital discharge records. Multivariable logistic regression was used to control for demographic and statin characteristics. Between 2006 and 2011 289,666 new statin users were identified with 238,855 (82.5%) receiving the statin for primary prevention compared to 50,811 (17.5%) who received it for secondary prevention. The secondary prevention group was 1.55 (95% CI 1.51-1.59) times as likely to be adherent and 0.67 (95% CI 0.65-0.69) times as likely to discontinue statin treatment than the primary prevention group. An early gap in statin coverage increased the odds of discontinuing statin treatment. Adherence to statin medication is higher in secondary prevention than primary prevention. Within each group, a range of demographic and treatment factors further influences adherence.

Annals for Educators - 17 November 2020.

Annals for Educators - 17 November 2020.

One-year statin persistence and adherence in adults with HIV in the United States

Statin persistence and adherence are low among US adults. Most individuals with HIV in the US have high adherence to antiretroviral therapy (ART), but less is known about their statin persistence and adherence. We analyzed persistence and adherence to statin therapy among adults with and without HIV. We analyzed claims data from adults in the MarketScan database who initiated statin therapy between 2007 and 2016. People with HIV (n=5619) were frequency matched 1-to-4 to those without HIV (n=22,476) based on age, sex, and calendar year of statin initiation. Statin persistence was defined by having dispensed statin medication during the last 90 days of the 365 days following initiation. High statin adherence was defined as a proportion of days covered (PDC) ≥0.80 during the 365 days following initiation. Among people with HIV, the PDC for each ART was calculated. The mean age of the study population was 51 years and 85.8% were men. Statin persistence was higher among adults with versus without HIV (72.8% versus 65.2%, multivariable-adjusted prevalence ratio 1.13, 95%CI 1.11-1.15). Among those who were persistent, a higher proportion of people with versus without HIV had high statin adherence (69.6% versus 59.9%, multivariable-adjusted prevalence ratio 1.16, 95%CI 1.13-1.19). Among people with HIV and high ART adherence (minimum PDC ≥0.90), 34.6% had a PDC for statin therapy <0.80. Adults with HIV were more persistent and adherent to statin medications versus those without HIV. However, a high proportion of adults with HIV had low statin adherence.

PAD patients present with poorer lipid target attainment than polyvascular patients – a call for intensified treatment

Abstract Background Due to the very high risk of future cardiovascular events, strict lipid lowering therapy is recommended in patients with peripheral artery disease (PAD). However, data on target level attainment and statin adherence is scarce, especially when the atherosclerotic burden is extended to other vascular beds, i.e. coronary artery disease (CAD) and/ or cerebrovascular disease (CeVD). Purpose We hypothesized that patients with PAD alone have poorer lipid target attainment than polyvascular patients (+ CAD and/ or CeVD) and that an intensified statin therapy improves attainment of lipid targets and thus survival of patients with PAD only. Methods Single center longitudinal observational study with 1380 symptomatic PAD patients over a mean follow-up period of 60±32 months. We related statin adherence and LDL-C target attainment to all-cause mortality. Results Initially, 58% of the PAD only patients were on statins in contrast to PAD patients with one (+1V (79%)) or two (+2V (80%)) further vascular regions. At follow up we observed an increase to 87% statin use (p&amp;lt;0.0001) in PAD only patients. Statin use in +1V and +2V patients increased as well (+1V: 92%; +2V: 87%). Lipid target attainment in PAD only (&amp;lt;55 mg/dl) was observed in only 10%, but increased to 19%. Statin dosage in PAD only patients, normalized to simvastatin 40 mg, increased from 46 to 52 mg/ day (p&amp;lt;0.01), and was paralleled by a mean decrease of LDL-C from 103 to 84 mg/ dL (p&amp;lt;0.0001). PAD only patients had a significant lower mortality rate (13%) than +1V (22%) or +2V patients (35%) (p&amp;lt;0.0001). Survival of PAD only patients significantly improved when having newly received a statin (11%), similar to those continuously on statins (10%). Moreover, patients on a high intensity statin medication had a low mortality of 10%. Those who terminated statin medication or never received a statin had a higher mortality (26%; p&amp;lt;0.01). Conclusion Patients with a PAD only have a lower mortality than PAD patients where progression to one or two vascular beds occurred. Our data suggest that for PAD only patients an intensified statin therapy is then associated with reduced mortality. A strategy of intensive and sustained statin therapy as early as possible is recommended. PAD only Statin Therapy outcomes Funding Acknowledgement Type of funding source: None

Drug related metabolites and genetic polymorphisms predict low low-density lipoprotein cholesterol response to atorvastatin treatment in patients with coronary heart disease

Abstract Background There is considerable individual variation in the low-density lipoprotein cholesterol (LDL-C) reduction at all classes and doses of statins. Knowledge of the determinants of individual variation LDL-C response upon statin treatment may pave the way for personalized and optimized statin treatment. Purpose We aimed to determine clinical and drug related predictors of variability of LDL-C response to atorvastatin 40 mg in patients with coronary heart disease. Methods This is an explorative study among 70 patients enrolled in the MUscle Side-Effects of atorvastatin in coronary patients (MUSE) randomized double blinded cross-over trial. Absolute and relative changes in LDL-C after 7 weeks treatment with atorvastatin 40 mg/day and 7 weeks treatment with placebo, were calculated for each patient. Linear regression analyses were applied to investigate the association between clinical (10 variables) and drug related (atorvastatin and/or metabolites, 18 variables) predictors and changes in LDL-C. Results Adherence to allocated treatment was high as confirmed by atorvastatin levels in blood and a mean proportion of days covered of 99% (range 91–100%). Mean reduction in LDL-C on atorvastatin treatment (LDL-C atorvastatin – LDL-C placebo) was 2.1 (SD 0.7, range 0.3 to 3.4) mmol/L. Mean percentage reduction in LDL-C was 51.1 (SD 11.2, range 29 to 60)%, and 37 patients (52.9%) had &amp;lt;50% LDL-C reduction. Genetic polymorphisms in SLCO1B1 or CYP3A (B 0.06, 95% CI 0.01 to 0.12, p=0.026), increasing number of coronary events (B 0.06, 95% CI 0.002 to 0.10, p=0.005), increasing trough concentration of 4-OH atorvastatin lactone (B 0.05, 95% CI 0.01 to 0.08, p=0.005) and increasing trough concentration of 4-OH atorvastatin acid (B 0.05, 95% CI 0.01 to 0.08, p=0.006) were the significant determinants of lower relative change (%) in LDL-C, in adjusted analyses. Age, gender, somatic comorbidity, cardiovascular risk factors, statin dependent muscle side-effects and other clinical and drug related determinants were not associated with changes in LDL-C. Conclusions There is considerable inter-individual variation in the LDL-C response upon treatment with atorvastatin despite confirmed high statin adherence. This is the first study reporting that genetic polymorphisms involved in the metabolism of statins and atorvastatin metabolites predict lower LDL-C response. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Association of Health, Grant/Award

The association of GATM polymorphism with statin-induced myopathy: a systematic review and meta-analysis

PurposeStatin-induced myopathy (SIM) is the commonest reason for discontinuation of statin therapy. The aim of this present meta-analysis is to assess the relationship between glycine amidinotransferase gene (GATM) polymorphism and risk of SIM.MethodsMEDLINE, EMBASE, Web of Science, and Cochrane Library databases were searched systematically for case-control studies investigating the relationship between GATM polymorphism and SIM. Retrieved articles were carefully reviewed and assessed according to the inclusion criteria. Associations were assessed in pooled data by calculating odds ratio with 95% confidence intervals. Subgroup analysis was performed according to comedications and severity of SIM.ResultsSix studies with 707 cases and 2321 controls were included in this meta-analysis. GATM rs9806699 G>A was associated with decreased risk of SIM (OR = 0.80, 95% CI 0.68–0.94, P = 0.006). This association remained significant in the subgroup with fibrates or niacin excluded. However, the association of rs9806699 G>A with severe SIM was not significant. In addition, another two variations at GATM, rs1719247 C>T, and rs1346268 T>C were also associated with declined risk of SIM.ConclusionsGATM polymorphism including rs9806699 G>A, rs1719247 C>T, and rs1346268 T>C may be protective factors of SIM. GATM rs9806699 G>A may only exert protective effect on mild SIM cases. Our meta-analysis indicates that GATM polymorphism may represent a pharmacogenomics biomarker for predicting incidence of SIM, which contributes to risk stratification and optimizing statin adherence.

The influence of statin withdrawal and adherence on stroke outcomes.

With multiple proven benefits, statin therapy has become the most critical advance in stroke prevention. We aimed to evaluate the risk factors and the effect of poor adherence or statin interruption on the clinical outcomes of ischemic stroke. This prospective cohort study included patients admitted with acute ischemic stroke between 2014 and 2018. Consecutive patients were distinguished into subgroups according to the adherence and withdrawal of statin. All participants were followed for 24months. The outcomes included stroke recurrence, major cardiovascular events, all-cause mortality, and functional performance. Functional outcome was assessed using the modified Rankin Scale at 7days, 30days, 6months, and 2years after hospital admission for ischemic stroke. In a secondary analysis, outcome variables were compared with statin-naïve patients. We included 479 patients with acute ischemic stroke. The mean age was 58.3, and 55.0% were male. There were 96 (21.8%) patients who received no statin, 150 (34.9%) patients with poor adherence, 40 (9.1%) patients with intermediate adherence, and 154 (35.0%) patients with good adherence. There were 54 (15.7%) cases of withdrawal of treatment. Patients with hypertension, previous stroke, and large-artery atherosclerosis were associated with poor adherence (p< 0.05). Those with poor adherence were significantly associated with worse functional outcomes and a higher incidence of stroke recurrence (p< 0.05). Significant functional recovery was just seen in patients with satisfactory adherence. The suboptimal use of statins is associated with significantly worse clinical outcomes in stroke patients.

Effect of Patient Financial Incentives on Statin Adherence and Lipid Control

Financial incentives can improve medication adherence and cardiovascular disease risk, but the optimal design to promote sustained adherence after incentives are discontinued is unknown. To determine whether 6-month interventions involving different financial incentives to encourage statin adherence reduce low-density lipoprotein cholesterol (LDL-C) levels from baseline to 12 months. This 4-group, randomized clinical trial was conducted from August 2013 to July 2018 among several large US insurer or employer populations and the University of Pennsylvania Health System. The study population included adults with elevated risk of cardiovascular disease, suboptimal LDL-C control, and evidence of imperfect adherence to statin medication. Data analysis was performed from July 2017 to June 2019. The interventions lasted 6 months during which all participants received daily medication reminders and an electronic pill bottle. Statin adherence was measured by opening the bottle. For participants randomized to the 3 intervention groups, adherence was rewarded with financial incentives. The sweepstakes group involved incentives for daily adherence. In the deadline sweepstakes group, incentives were reduced if participants were adherent only after a reminder. The sweepstakes plus deposit contract group split incentives between daily adherence and a monthly deposit reduced for each day of nonadherence. The primary outcome was change in LDL-C level from baseline to 12 months. Among 805 participants randomized (199 in the simple daily sweepstakes group, 204 in the deadline sweepstakes group, 201 in the sweepstakes plus deposit contract group, and 201 in the control group), the mean (SD) age was 58.5 (10.3) years; 519 participants (64.5%) were women, 514 (63.9%) had diabetes, and 273 (33.9%) had cardiovascular disease. The mean (SD) baseline LDL-C level was 143.2 (42.5) mg/dL. Measured adherence at 6 months (defined as the proportion of 180 days with electronic pill bottle opening) in the control group (0.69; 95% CI, 0.66-0.72) was lower than that in the simple sweepstakes group (0.84; 95% CI, 0.81-0.87), the deadline sweepstakes group (0.86; 95% CI, 0.83-0.89), and the sweepstakes plus deposit contract group (0.87; 95% CI, 0.84-0.90) (P < .001 for each incentive group vs control). LDL-C levels were measured for 636 participants at 12 months. Mean LDL-C level reductions from baseline to 12 months were 33.6 mg/dL (95% CI, 28.4-38.8 mg/dL) in the control group, 32.4 mg/dL (95% CI, 27.3-37.6 mg/dL) in the sweepstakes group, 33.2 mg/dL (95% CI, 28.1-38.3 mg/dL) in the deadline sweepstakes group, and 36.5 mg/dL (95% CI, 31.3-41.7 mg/dL) in the sweepstakes plus deposit contract group (adjusted P > .99 for each incentive group vs control). Compared with the control group, different financial incentives improved measured statin adherence but not LDL-C levels. This result points to the importance of directly measuring health outcomes, rather than simply adherence, in trials aimed at improving health behaviors. ClinicalTrials.gov Identifier: NCT01798784.

Patient-reported barriers to statin adherence: Excerpts from a motivational interviewing intervention in older adults

ObjectiveDespite a known benefit in the reduction of cardiovascular risk, adherence to statins remains suboptimal. A qualitative analysis was conducted within an intervention that identified trajectories of statin adherence in patients and used motivational interviewing (MoI) to improve adherence. The objective of this qualitative study was to evaluate transcripts of an MoI telephonic intervention to identify potential, past, and current barriers to statin adherence and barriers specific to distinct adherence trajectories. MethodsThe MoI intervention was customized by past 1-year adherence trajectories (rapid discontinuation, gradual decline, and gaps in adherence). Two authors independently extracted and documented barriers from phone transcripts. Themes were derived from literature a priori and by cataloging recurring themes from the transcripts. ResultsThe transcripts of calls made to 157 patients were reviewed of which 25.2% did not communicate a specific adherence barrier despite falling into a low-adherence trajectory when examining refill data. The most commonly reported barriers to statin adherence included adverse effects (40.1%), forgetfulness (30.0%), and lack of skills or knowledge pertaining to statins (25%). More patients in the rapid discontinuation group perceived medication as unnecessary, whereas more patients in the gaps in adherence group reported a communication barrier with their health care provider. Several barriers among patients who fell into low-adherence trajectories were reported. Some patients did not report any barriers, which may have indicated denial. MoI phone calls were useful in providing knowledge, clarifying medication regimens, and reinforcing the need to take statins. ConclusionThis study identified patient-reported barriers to statin adherence elicited during an MoI telephonic intervention conducted by student pharmacists. There were differences in barriers reported by patients from each trajectory, which emphasize the need for additional tailored interventions to improve patient adherence.

The effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis: A systematic review and meta-analysis

BackgroundIdiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function. MethodsMedline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy. ResultsFive studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72–0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68–1.12). There was no statistically significant association between statin use and decline in FVC % predicted. ConclusionThere is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment. PROSPERO registration numberCRD42019122745.

Interventions to Improve Adherence to Cardiovascular Medication: What About Gender Differences? A Systematic Literature Review.

BackgroundCompared to men, women have lower treatment rates for cardiovascular disease (CVD), are at higher risk for medication non-adherence and have different reasons for being non-adherent. The aim of this study was to synthesize and evaluate gender-specific adherence-promoting interventions for cardiovascular medication and gender-specific effects of gender-neutral interventions.MethodsA systematic literature search was performed in PubMed, Embase, PsycINFO, CINAHL and Cochrane Library from January 2007 to October 2019. Intervention studies (with control group) aimed at improving cardiovascular medication adherence with minimally 14 weeks follow-up were included. Two reviewers independently screened titles and abstracts. Full text was obtained for selected abstracts and screened for final inclusion. Data extraction included gender-specific targeting or analysis.ResultsThe search identified 6502 citations. After screening title and abstract, full text was obtained from 127 potentially eligible articles. Ultimately, 11 articles were included that analyzed gender differences in gender-neutral interventions. Two reported a gender-specific intervention effect. Using an electronic reminder device, one study increased statin adherence in women. The other found a larger increase in adherence to CVD medication following telephone counseling for men than women. Nine studies did not identify a gender-specific effect.ConclusionDespite differences in levels of and reasons for non-adherence, most studies addressing adherence did not analyze potential differences in effect by gender. Moreover, none of the identified studies used gender-specific adherence promoting interventions. Increasing awareness about gender differences in adherence might lead to better tailoring of interventions to gender-specific needs and better results in improving adherence.

A retrospective cohort study evaluating the relationship between statin medication adherence and economic outcomes in commercial health plans

Adherence to statin medications is suboptimal; however, the association of statin adherence, as defined in medication adherence quality measures, with healthcare service use and expenditure within one year has not been assessed in a commercially insured United States (US) population. To investigate the relationship between statin adherence, as specified in the Pharmacy Quality Alliance (PQA) statin medication adherence quality measure, and healthcare resource utilization and expenditures within commercial health plans over a one-year period. This one-year retrospective analysis involved a cohort of individuals from the Truven Health MarketScan Commercial Claims and Encounters Research Databases (2009-2015). Generalized linear models with log link and negative binomial distribution (use) or gamma distribution (expenditures) were used to assess relationships between medication adherence (≥80% proportion of days covered) and healthcare use and expenditures (adjusted to 2015 US dollars) while adjusting for covariates. Beta coefficients were used to compute cost ratios (CR) and rate ratios (RR). An alpha level of 0.001 was set a priori. Of 4,450,308 eligible individuals, 2,757,288 (61.9%) were classified as adherent. Multivariable analyses indicated adherent individuals had more outpatient (RR=1.009, 95% CI=1.007, 1.010) and fewer inpatient visits (RR=0.756, 95% CI=0.749, 0.762); and lower outpatient (CR=0.965, 95% CI=0.963, 0.967), inpatient (CR=0.780, 95% CI=0.779, 0.782), and total expenditures (CR=0.975, 95% CI=0.973, 0.977). Adherence was associated with lower per member per month total healthcare expenditures ($18.91) vs nonadherence. Within one year, statin adherence was associated with more outpatient and fewer inpatient visits, lower outpatient and inpatient expenditures, and lower total expenditures than nonadherence, within a commercially-insured population.

Interventions to Improve Statin Tolerance and Adherence in Patients at Risk for Cardiovascular Disease : A Systematic Review for the 2020 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Management of Dyslipidemia.

Strategies to improve patients' tolerance of and adherence to statins may enhance the effectiveness of dyslipidemia treatment in those at risk for cardiovascular disease (CVD). To assess the benefits and harms of interventions to improve statin adherence in patients at risk for CVD. MEDLINE, EMBASE, PubMed, and the Cochrane Library from December 2013 through May 2019 (English language only). Systematic reviews (SRs), randomized controlled trials (RCTs), and cohort studies that addressed interventions for improving statin tolerance and adherence. One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy. One SR, 1 RCT, and 4 cohort studies were included. The SR found that intensified patient care improved adherence and decreased levels of total serum cholesterol and low-density lipoprotein cholesterol (LDL-C) at 6 months or more of follow-up. Compared with statin treatment discontinuation, nondaily statin dosing lowered total cholesterol and LDL-C levels. One large cohort study suggested that more than 90% of patients who discontinued statin treatment could be rechallenged with the same or a different statin and be adherent 1 year after a statin-related adverse event led to discontinuation. Two small cohort studies reported that more than 90% of patients who were previously intolerant to statins and who had low baseline levels of vitamin D were able to adhere to statins 1 year after vitamin D supplementation. This is a qualitative synthesis of new evidence with existing meta-analyses, and studies had several methodological shortcomings. Although the strength of evidence for most interventions was low or very low, intensified patient care and rechallenge with the same or a different statin (or a lower dose) seem to be favorable options for improving statin adherence. U.S. Department of Veterans Affairs.

Evaluation of Aspirin and Statin Therapy Use and Adherence in Patients With Premature Atherosclerotic Cardiovascular Disease

Studies on the use of and adherence to secondary prevention therapies in patients with premature and extremely premature atherosclerotic cardiovascular disease (ASCVD) are lacking. To evaluate and compare aspirin use, any statin use, high-intensity statin use, and statin adherence among patients with premature or extremely premature ASCVD compared with patients with nonpremature ASCVD. This multicenter cross-sectional study used the clinical and administrative data sets of the US Department of Veterans Affairs (VA) to identify adult patients with at least 1 primary care visit in the VA health care system between October 1, 2014, and September 30, 2015. The study cohort comprised patients with ASCVD (ischemic heart disease, peripheral arterial disease, or ischemic cerebrovascular disease) who were enrolled in the Veterans With Premature Atherosclerosis (VITAL) registry. Patients with missing data for date of birth or sex and those with limited life expectancy were excluded. Data were analyzed from November 1, 2019, to January 1, 2020. Premature (the first ASCVD event occurred at age <55 years for men and age <65 years for women) vs nonpremature (the first ASCVD event occurred at age ≥55 years for men or age ≥65 years for women) ASCVD and extremely premature (the first ASCVD event occurred at age <40 years) vs nonpremature ASCVD. The primary outcomes were aspirin use, any statin use, high-intensity statin use, and statin adherence (measured by proportion of days covered [PDC] ≥0.8). Of the 1 248 158 patients identified, 135 703 (10.9%) had premature ASCVD (mean [SD] age, 49.6 [5.8] years; 116 739 men [86.0%]), 1 112 455 (89.1%) had nonpremature ASCVD (mean [SD] age, 69.6 [8.9] years; 1 104 318 men [99.3%]), and 7716 (0.6%) had extremely premature ASCVD (mean [SD] age, 34.2 [4.3] years; 6576 men [85.2%]). Patients with premature ASCVD vs those with nonpremature ASCVD had lower rates of aspirin use (96 468 [71.1%] vs 860 726 [77.4%]; P < .001) and any statin use (98 908 [72.9%] vs 894 931 [80.5%]; P < .001); had a statin PDC of 0.8 or higher (57 306 [57.9%] vs 644 357 [72.0%]; P < .001); and a higher rate of high-intensity statin use (49 354 [36.4%] vs 332 820 [29.9%]; P < .001). Similarly, patients with extremely premature ASCVD were less likely to use aspirin (odds ratio [OR], 0.27; 95% CI, 0.26-0.29), any statin (OR, 0.25; 95% CI, 0.24-0.27), or high-intensity statin (OR, 0.78; 95% CI, 0.74-0.82) and to be statin adherent (OR, 0.44; 95% CI, 0.41-0.47). In this study, patients with premature or extremely premature ASCVD appeared to be less likely to use aspirin or statins and to adhere to statin therapy. This finding warrants further investigation into premature ASCVD and initiatives, including clinician and patient education, to better understand and mitigate the disparities in medication use and adherence.

Statin adherence and risk of all-cause, cancer, and cardiovascular mortality among dyslipidemia patients: A time-dependent analysis

Background and aimResults have been mixed and uncertainty still remains regarding the impact of statin adherence on premature deaths. Thus, we investigated the association between statin adherence and risks of all-cause, cancer, and cardiovascular mortality among dyslipidemia patients in South Korea. Methods and resultsWe used data from the National Health Insurance Service (NHIS) National Sample Cohort for the years 2003–2013, which included data on 107,954 middle-aged and elderly dyslipidemia patients. Among these patients, a time-dependent Cox proportional hazards model was used to estimate the hazard ratios (HRs) of all-cause, cancer, and cardiovascular mortality depending on proportion of days covered (PDC) by statin medication. A total of 3073 (2.85%) individuals died within the study period. Of these individuals, 1143 (1.06%) died from cancer, and 687 (0.64%) died from cardiovascular diseases. Relative to good medication adherence (>80%), moderate (50–80%) (hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.14–1.43) and poor (<50%) (HR: 1.58, 95% CI: 1.41–1.78) adherence were associated with increased risk of all-cause mortality. Poor adherence was also associated with increased risk of cancer (HR: 1.33, 95% CI: 1.16–1.52) and cardiovascular (HR: 1.27, 95% CI: 1.06–1.51) mortality. ConclusionSuch findings reveal that relative to good statin adherence, moderate and/poor adherence is associated with increased risks of all-cause, cancer, and cardiovascular mortality. Clinicians should assess for dyslipidemia, link statin adherence problems to potential mortality risk, and monitor outcomes in both medication adherence and disease complications.