Browsing by Subject "Hydroxymethylglutaryl-CoA Reductase Inhibitors"

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Open Access
A protocol to evaluate the efficacy, perceptions, and cost of a cholesterol packaging approach to improve medication adherence.
(Contemporary clinical trials, 2014-09) Zullig, Leah L; Pathman, Joshua; Melnyk, S Dee; Brown, Jamie N; Sanders, Linda L; Koropchak, Celine; Howard, Teresa; Danus, Susanne; McCant, Felicia; Bosworth, Hayden B
Purpose
Elevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor for cardiovascular disease (CVD), a leading cause of death in the United States. Despite clinical practice guidelines aimed at facilitating LDL-C control, many Veterans do not achieve guideline-recommended LDL-C levels.
Methods
We describe a study focused on VA healthcare system users at risk for CVD (i.e., LDL-C level >130 mg/dl and/or <80% cholesterol pill refill adherence in the last 12 months). We are conducting a two and a half year randomized controlled trial (i.e., intervention administered over 12 months) among Veterans with uncontrolled cholesterol receiving care at select VA-affiliated primary care clinics in North Carolina. We anticipate enrolling 250 diverse patients (10% women; 40% African American). Patients are randomized to an educational control group or intervention group. Intervention group participants' medication is provided in special blister packaging labeled for daily use that includes reminders; MeadWestvaco Corporation's pre-filled DosePak® contains standard doses of statins in accordance with the existing prescriptions.
Conclusions
Pre-filled blister packaging may provide an inexpensive solution to improve medication adherence. Our study enrolls a diverse sample and provides information about whether an adherence packaging intervention can: 1) improve medication adherence; 2) improve patients' LDL-C levels; 3) be well received by patients and providers; and 4) provide a cost effective solution to improve medication adherence.
Open Access
Co-occurring reasons for medication nonadherence within subgroups of patients with hyperlipidemia.
(Journal of behavioral medicine, 2019-04) Blalock, Dan V; Bosworth, Hayden B; Reeve, Bryce B; Voils, Corrine I
Medication nonadherence is a significant clinical problem among individuals taking statins. Poor adherence is often attributable to several reasons, yet most adherence interventions target a single reason. Baseline data were examined from a randomized clinical trial of 236 patients with hyperlipidemia. A latent class analysis was then performed on patients reporting any nonadherence (n = 109). A 4-class solution provided the most optimal fit and differentiation of classes. Class 1 (N = 59, 54%) included patients who reported occasionally forgetting. Class 2 (N = 16, 14%) represented patients who were concerned about side effects. Class 3 (N = 17, 16%) represented patients who reported out-of-routine life events as contributing to nonadherence. Class 4 (N = 17, 16%) represented patients who endorsed a large number reasons indiscriminately. Class membership was almost uniformly unrelated to any patient demographic factors or treatment arm. Each cluster of reasons defining these patients may be best addressed through different intervention strategies.
Open Access
Comparison of Clinical Care and In-Hospital Outcomes of Asian American and White Patients With Acute Ischemic Stroke.
(JAMA neurology, 2019-04) Song, Sarah; Liang, Li; Fonarow, Gregg C; Smith, Eric E; Bhatt, Deepak L; Matsouaka, Roland A; Xian, Ying; Schwamm, Lee H; Saver, Jeffrey L
Importance:Although overall stroke incidence and mortality in the United States is improving, little is known about the characteristics and clinical outcomes of acute ischemic stroke in Asian American individuals. Objective:To compare the characteristics, care, and outcomes of Asian American and white patients with acute ischemic stroke. Design, Setting, Participants:Retrospective analysis of Asian American and white patients admitted with a primary diagnosis of acute ischemic stroke to hospitals participating in the Get With The Guidelines-Stroke (GWTG-Stroke) program between April 1, 2004, and July 31, 2016. The GWTG-Stroke database is a prospectively collected stroke quality improvement registry sponsored by the American Heart Association/American Stroke Association. Main Outcomes and Measures:Multivariable logistic regression models assessed the association of Asian American race/ethnicity, clinical outcomes, and quality measures. Results:The study population of 1 772 299 patients (mean [SD] age, 72.4 [14.2] years; 51.3% female) consisted of 64 337 Asian American patients (3.6%) and 1 707 962 white patients (96.4%) admitted to 2171 GWTG-Stroke hospitals with acute ischemic stroke. After adjustment for patient and hospital variables, Asian American patients were seen with greater stroke severity compared with white patients (National Institutes of Health Stroke Scale [NIHSS] score ≥16) (odds ratio [OR], 1.35; 95% CI, 1.30-1.40; P < .001), manifested higher in-hospital mortality (OR, 1.14; 95% CI, 1.09-1.19; P < .001), had longer length of stay (OR, 1.17; 95% CI, 1.14-1.20; P < .001), and were less likely to ambulate independently at discharge (OR, 0.84; 95% CI, 0.79-0.90; P < .001). Although Asian American patients had fewer intravenous tissue plasminogen activator (IV tPA) administrations than white patients (OR, 0.95; 95% CI, 0.91-0.98; P = .003), they had more symptomatic hemorrhage after tPA (OR, 1.36; 95% CI, 1.20-1.55; P < .001) and overall post-tPA complications (OR, 1.31; 95% CI, 1.18-1.46; P < .001). Asian American patients had better quality measure adherence overall than white patients, including rehabilitation (OR, 1.27; 95% CI, 1.18-1.36; P < .001), door to tPA within 60 minutes (OR, 1.14; 95% CI, 1.06-1.22; P < .001), and intensive statin therapy (OR, 1.14; 95% CI, 1.10-1.18; P < .001). After adjustment for stroke severity, Asian American patients had lower in-hospital mortality than white patients (OR, 0.95; 95% CI, 0.91-0.99; P = .008). Conclusions and Relevance:Asian American patients manifested more severe ischemic strokes, were less likely to receive IV tPA, and had worse functional outcomes than white patients. These findings warrant additional research toward improving clinical outcomes for Asian American patients with acute ischemic stroke.
Open Access
Design and rationale of the LAPLACE-TIMI 57 trial: a phase II, double-blind, placebo-controlled study of the efficacy and tolerability of a monoclonal antibody inhibitor of PCSK9 in subjects with hypercholesterolemia on background statin therapy.
(Clinical cardiology, 2012-01) Kohli, Payal; Desai, Nihar R; Giugliano, Robert P; Kim, Jae B; Somaratne, Ransi; Huang, Fannie; Knusel, Beat; McDonald, Shannon; Abrahamsen, Timothy; Wasserman, Scott M; Scott, Robert; Sabatine, Marc S
Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone for the prevention of atherosclerotic heart disease, improving clinical outcomes and reducing vascular mortality in patients with hypercholesterolemia. The clinical benefits of LDL-C reduction appear to extend even to patients starting with LDL-C as low as 60-80 mg/dL prior to initiating therapy. Statins are the first-line agents for treating hypercholesterolemia and are effective in reducing LDL-C, but many patients are unable to achieve their optimal lipid targets despite intensive statin therapy. Therefore, there has been a strong impetus for the development of novel pharmacologic agents designed to lower LDL-C further in patients already on statin therapy. Genetic mutations resulting in altered cholesterol homeostasis provide valuable information regarding novel approaches for treating hypercholesterolemia. To that end, mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) were linked to altered levels of LDL-C, illustrating this protein's role in lipid metabolism. PCSK9 promotes degradation of the LDL receptor, preventing its transport back to the cell surface and thereby increasing circulating LDL-C. Conversely, inhibition of PCSK9 can profoundly decrease circulating LDL-C, and thus is an attractive new target for LDL-C-lowering therapy. AMG 145 is a fully human monoclonal immunoglobulin G2 antibody that binds specifically to human PCSK9 and inhibits its interaction with the low-density lipoprotein receptor. In this manuscript, we describe the rationale and design of LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-Thrombolysis In Myocardial Infarction 57 (LAPLACE-TIMI 57; NCT01380730), a 12-week, randomized, double-blind, dose-ranging, placebo-controlled study designed to assess the safety and efficacy of AMG 145 when added to statin therapy in patients with hypercholesterolemia.
Open Access
Evaluation of a packaging approach to improve cholesterol medication adherence.
(The American journal of managed care, 2017-09) Bosworth, Hayden B; Brown, Jamie N; Danus, Susanne; Sanders, Linda L; McCant, Felicia; Zullig, Leah L; Olsen, Maren K
Elevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor for cardiovascular disease, a leading cause of death in the United States. Our goal was to evaluate a simple, scalable, and affordable medication packaging method for improving cholesterol medication adherence and subsequently lowering LDL-C levels.Mixed-method study.This mixed-method study involved US military veterans with LDL-C levels greater than 130 mg/dL and/or less than 80% refill adherence of cholesterol-lowering medication in the last 12 months; they were randomized to an education-only (control) group or an adherence packaging intervention group. Adherence packaging group participants' statin medication was provided in special blister packaging labeled for daily use that included written reminder prompts. Outcomes included 12-month cholesterol medication possession ratio (MPR) for medication refills; baseline, 6-, and 12-month self-reported cholesterol medication use; LDL-C and high-density lipoprotein cholesterol (HDL-C) levels; and total cholesterol changes over 12 months. Qualitative evaluation of the intervention is presented as well.We enrolled 240 individuals (120 intervention, 120 control). Overall, 54.2% of the adherence packaging intervention group was adherent per MPR over 12 months compared with 46.6% of the education-only group (difference = 7.6%; 95% confidence interval, -5% to 20%; P ≤.24). Both arms reported improvements in self-reported cholesterol adherence at 12 months, and decreases in LDL-C, HDL-C, and total cholesterol were observed, but differences in change between arms were not statistically significant. Qualitatively, patients reported high levels of satisfaction with the blister package.In a sample of US veterans, prefilled calendared blister packaging provided an inexpensive method for improving cholesterol medication adherence.
Open Access
HIV and Hepatitis C-Coinfected Patients Have Lower Low-Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent "PCSK9-Lipid Paradox".
(Journal of the American Heart Association, 2016-04) Kohli, Payal; Ganz, Peter; Ma, Yifei; Scherzer, Rebecca; Hur, Sophia; Weigel, Bernard; Grunfeld, Carl; Deeks, Steven; Wasserman, Scott; Scott, Rob; Hsue, Priscilla Y
Background
Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and improve outcomes in the general population. HIV-infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus (HCV) coinfection, making PCSK9 inhibition a potentially attractive therapy.
Methods and results
We studied 567 participants from a clinic-based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL-C level was 100 mg/dL (IQR 77-124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol, LDL-C, and high-density lipoprotein cholesterol levels were lower in coinfected patients compared with controls (P<0.001). PCSK9 was 21% higher in HIV/HCV-coinfected patients versus controls (95% CI 9-34%, P<0.001) and 11% higher in coinfected individuals versus those with HIV infection alone (95% CI 3-20%, P=0.008). After adjustment for cardiovascular risk factors, HIV/HCV coinfection remained significantly associated with 20% higher PCSK9 levels versus controls (95% CI 8-33%, P=0.001). Interleukin-6 levels increased in a stepwise fashion from controls (lowest) to HIV-infected to HIV/HCV-coinfected individuals (highest) and correlated with PCSK9 (r=0.11, P=0.018).
Conclusions
Despite having lower LDL-C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin-6. Clinical trials should be conducted to determine the efficacy of targeted PCSK9 inhibition in the setting of HIV/HCV coinfection.
Open Access
ImPlementation REsearCh to DEvelop Interventions for People Living with HIV (the PRECluDE consortium): Combatting chronic disease comorbidities in HIV populations through implementation research.
(Progress in cardiovascular diseases, 2020-03) Gamble-George, Joyonna Carrie; Longenecker, Christopher T; Webel, Allison R; Au, David H; Brown, Arleen F; Bosworth, Hayden; Crothers, Kristina; Cunningham, William E; Fiscella, Kevin A; Hamilton, Alison B; Helfrich, Christian D; Ladapo, Joseph A; Luque, Amneris; Tobin, Jonathan N; Wyatt, Gail E; Implementation Research to Develop Interventions for People Living with HIV (PRECluDE) Consortium
Antiretroviral therapy (ART) prevented premature mortality and improved the quality of life among people living with the human immunodeficiency virus (PLWH), such that now more than half of PLWH in the United States are 50 years of age and older. Increased longevity among PLWH has resulted in a significant rise in chronic, comorbid diseases. However, the implementation of guideline-based interventions for preventing, treating, and managing such age-related, chronic conditions among the HIV population is lacking. The PRECluDE consortium supported by the Center for Translation Research and Implementation Science at the National Heart, Lung, and Blood Institute catalyzes implementation research on proven-effective interventions for co-occurring heart, lung, blood, and sleep diseases and conditions among PLWH. These collaborative research studies use novel implementation frameworks with HIV, mental health, cardiovascular, and pulmonary care to advance comprehensive HIV and chronic disease healthcare in a variety of settings and among diverse populations.
Open Access
Meta-analysis of Placebo-Controlled Randomized Controlled Trials on the Prevalence of Statin Intolerance.
(Am J Cardiol, 2017-09-01) Riaz, Haris; Khan, Abdur Rahman; Khan, Muhammad Shahzeb; Rehman, Karim Abdur; Alansari, Shehab Ahmad Redha; Gheyath, Bashaer; Raza, Sajjad; Barakat, Amr; Luni, Faraz Khan; Ahmed, Haitham; Krasuski, Richard A
The prevalence of intolerance varies widely. Stopping statin therapy is associated with worse outcomes in patients with cardiovascular disease. Despite extensive studies, the benefits and risks of statins continue to be debated by clinicians and the lay public. We searched the PubMed, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials of statins compared with placebo. Studies were included if they had ≥1,000 participants, had patients who were followed up for ≥1 year, and reported rates of drug discontinuation. Studies were pooled as per the random effects model. A total of 22 studies (statins = 66,024, placebo = 63,656) met the inclusion criteria. The pooled analysis showed that, over a mean follow-up of 4.1 years, the rates of discontinuation were 13.3% (8,872 patients) for statin-treated patients and 13.9% (8,898 patients) for placebo-treated patients. The random effects model showed no significant difference between the placebo and statin arms (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.93 to 1.06). The results were similar for both primary prevention (OR = 0.98, 95% CI = 0.92 to 1.05, p = 0.39) and secondary prevention (OR = 0.92, 95% CI = 0.83 to 1.05, p = 0.43) studies. The pooled analysis suggested that the rates of myopathy were also similar between the statins and placebos (OR = 1.2, 95% CI = 0.88 to 1.62, p = 0.25). In conclusion, this meta-analysis of >125,000 patients suggests that the rate of drug discontinuation and myopathy does not significantly differ between statin- and placebo-treated patients in randomized controlled trials. These findings are limited by the heterogeneity of results, the variable duration of follow-up, and the lower doses of statins compared with contemporary clinical practice.
Open Access
Metabolic Markers to Predict Incident Diabetes Mellitus in Statin-Treated Patients (from the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trials).
(The American journal of cardiology, 2016-11) Kohli, Payal; Knowles, Joshua W; Sarraju, Ashish; Waters, David D; Reaven, Gerald
The goal of this analysis was to evaluate the ability of insulin resistance, identified by the presence of prediabetes mellitus (PreDM) combined with either an elevated triglyceride (TG >1.7 mmol/l) or body mass index (BMI ≥27.0 kg/m²), to identify increased risk of statin-associated type 2 diabetes mellitus (T2DM). Consequently, a retrospective analysis of data from subjects without diabetes in the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels randomized controlled trials was performed, subdividing participants into 4 experimental groups: (1) normal fasting glucose (NFG) and TG ≤1.7 mmol/l (42%); (2) NFG and TG >1.7 mmol/l (22%); (3) PreDM and TG ≤1.7 mmol/l (20%); and (4) PreDM and TG >1.7 mmol/l (15%). Comparable groupings were created substituting BMI values (kg/m² <27.0 and ≥27.0) for TG concentrations. Patients received atorvastatin or placebo for a median duration of 4.9 years. Incident T2DM, defined by developing at least 2 fasting plasma glucose (FPG) concentrations ≥126 mg/dl, an increase in FPG ≥37 mg/dl, or a clinical diagnosis of T2DM, was observed in 8.2% of the total population. T2DM event rates (statin or placebo) varied from a low of 2.8%/3.2% (NFG and TG ≤1.7 mmol/l) to a high of 22.8%/7.6% (PreDM and TG >1.7 mmol/l) with intermediate values for only an elevated TG >1.7 mmol/l (5.2%/4.3%) or only PreDM (12.8%/7.6%). Comparable differences were observed when BMI values were substituted for TG concentrations. In conclusion, these data suggest that (1) the diabetogenic impact of statin treatment is relatively modest in general; (2) the diabetogenic impact is accentuated relatively dramatically as FPG and TG concentrations and BMI increase; and (3) PreDM, TG concentrations, and BMI identify people at highest risk of statin-associated T2DM.
Open Access
Novel application of approaches to predicting medication adherence using medical claims data.
(Health services research, 2019-12) Zullig, Leah L; Jazowski, Shelley A; Wang, Tracy Y; Hellkamp, Anne; Wojdyla, Daniel; Thomas, Laine; Egbuonu-Davis, Lisa; Beal, Anne; Bosworth, Hayden B
Objective
To compare predictive analytic approaches to characterize medication nonadherence and determine under which circumstances each method may be best applied.
Data sources/study setting
Medicare Parts A, B, and D claims from 2007 to 2013.
Study design
We evaluated three statistical techniques to predict statin adherence (proportion of days covered [PDC ≥ 80 percent]) in the year following discharge: standard logistic regression with backward selection of covariates, least absolute shrinkage and selection operator (LASSO), and random forest. We used the C-index to assess model discrimination and decile plots comparing predicted values to observed event rates to evaluate model performance.
Data extraction
We identified 11 969 beneficiaries with an acute myocardial infarction (MI)-related admission from 2007 to 2012, who filled a statin prescription at, or shortly after, discharge.
Principal findings
In all models, prior statin use was the most important predictor of future adherence (OR = 3.65, 95% CI: 3.34-3.98; OR = 3.55). Although the LASSO regression model selected nearly 90 percent of all candidate predictors, all three analytic approaches had moderate discrimination (C-index ranging from 0.664 to 0.673).
Conclusions
Although none of the models emerged as clearly superior, predictive analytics could proactively determine which patients are at risk of nonadherence, thus allowing for timely engagement in adherence-improving interventions.
Open Access
Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.
(BJU Int, 2014-11) Allott, EH; Howard, LE; Cooperberg, MR; Kane, CJ; Aronson, WJ; Terris, MK; Amling, CL; Freedland, SJ
OBJECTIVE: To investigate the effect of statin use after radical prostatectomy (RP) on biochemical recurrence (BCR) in patients with prostate cancer who never received statins before RP. PATIENTS AND METHODS: We conducted a retrospective analysis of 1146 RP patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analyses were used to examine differences in risk of BCR between post-RP statin users vs nonusers. To account for varying start dates and duration of statin use during follow-up, post-RP statin use was treated as a time-dependent variable. In a secondary analysis, models were stratified by race to examine the association of post-RP statin use with BCR among black and non-black men. RESULTS: After adjusting for clinical and pathological characteristics, post-RP statin use was significantly associated with 36% reduced risk of BCR (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47-0.87; P = 0.004). Post-RP statin use remained associated with reduced risk of BCR after adjusting for preoperative serum cholesterol levels. In secondary analysis, after stratification by race, this protective association was significant in non-black (HR 0.49, 95% CI 0.32-0.75; P = 0.001) but not black men (HR 0.82, 95% CI 0.53-1.28; P = 0.384). CONCLUSION: In this retrospective cohort of men undergoing RP, post-RP statin use was significantly associated with reduced risk of BCR. Whether the association between post-RP statin use and BCR differs by race requires further study. Given these findings, coupled with other studies suggesting that statins may reduce risk of advanced prostate cancer, randomised controlled trials are warranted to formally test the hypothesis that statins slow prostate cancer progression.
Open Access
Statin Adherence: Does Gender Matter?
(Current atherosclerosis reports, 2016-11) Goldstein, Karen M; Zullig, Leah L; Bastian, Lori A; Bosworth, Hayden B
Purpose of review
Cardiovascular disease (CVD) continues to be the leading cause of death for men and women in the USA. Statins have contributed significantly to noted declines in cardiovascular-related mortality in the last decade; however, the benefit of statins is inequitable across genders. Women continue to be less likely to take statins and to meet target LDL goals than men. As a possible contributing factor to this disparity, we explore the evidence for gender-based differences in provision of, and adherence to statins.
Recent findings
Compared with men, women are less likely to adhere to statins. Potential reasons for this gender difference in use of statins can be observed across all phases of adherence including both intentional and unintentional non-adherence. Notable gender-specific contributing factors for statin non-adherence include decreased provider and patient awareness of CVD risk among women, higher risk of statin intolerance among women, and competing demands associated with family caregiving responsibilities. Similar to limitations in the broader CVD literature, there is inadequate inclusion of gender-specific analyses in statin-related trials. Gender-based disparities in statin adherence can be linked to both provider level, psychosocial, and medication intolerance factors. Interventions designed to improve statin adherence should take gender-specific challenges into consideration such as women being older at the time of increased CVD risk, higher rates of statin intolerance, and potentially greater caregiving responsibilities.
Open Access
The Importance of Considering Clinical Inertia and Implementation Science When Addressing Medication Adherence.
(JAMA network open, 2020-10) Bosworth, Hayden B
Open Access
Therapy and clinical trials.
(Curr Opin Lipidol, 2011-12) Elmallah, Wael; Krasuski, Richard A
Open Access
Therapy and clinical trials.
(Curr Opin Lipidol, 2014-10) Chongthammakun, Vasutakarn; Krasuski, Richard A
Open Access
Therapy and clinical trials.
(Curr Opin Lipidol, 2013-06) Sodhi, Nishtha; Krasuski, Richard A
Open Access
Therapy and clinical trials.
(Curr Opin Lipidol, 2010-10) Devendra, Ganesh P; Krasuski, Richard A

Browsing by Subject "Hydroxymethylglutaryl-CoA Reductase Inhibitors"

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