Cholesterol-lowering Medications Research Articles

American Heart Association's Cholesterol CarePlan as a Smartphone-Delivered Web App for Patients Prescribed Cholesterol-Lowering Medication: Protocol for an Observational Feasibility Study.

BackgroundAdoption of healthy lifestyle and compliance with cholesterol-lowering medication reduces the risk of cardiovascular disease (CVD). The use of digital tools and mobile technology may be important for sustaining positive behavioral change.ObjectiveThe primary objective of this study is to evaluate the feasibility and acceptability of administering the Cholesterol CarePlan Web app developed by the American Heart Association aimed at improving lifestyle and medication adherence among patients prescribed cholesterol-lowering medication. The secondary objective is to assess the Web app’s efficacy.MethodsA prospective, observational feasibility study will be conducted to demonstrate whether the Web app may be successfully taken up by patients and will be associated with improved clinical and behavioral outcomes. The study will aim to recruit 180 study participants being prescribed cholesterol-lowering medication for at least 30 days across 14 general practices in London, England. Potentially eligible patients will be invited to use the Web app on a smartphone and visit general practice for three 20-minute clinical assessments of blood pressure, height, weight, smoking, and nonfasting cholesterol over 24 weeks. The feasibility of administering the Web app will be judged by recruitment and dropout statistics and the sociodemographic and comorbidity profile of consenting study participants, consenting nonparticipants, and all potentially eligible patients. Acceptability will be assessed using patients’ readiness to embrace new technologies, the usability of the Web app, and patient satisfaction. The efficacy of the Web app will be assessed by changes in medication adherence and clinical risk factors by levels of the Web app compliance.ResultsThis study is currently funded by the American Heart Association. Initial study recruitment will take place between February and July 2018 followed by patient follow-up. Patient level data will be obtained in January 2019. Data analysis will be completed by February 2019. Results will be submitted for publication in March 2019.ConclusionsThe potential of an app to improve patients’ lifestyle and management of cholesterol may inform the design of a randomized controlled trial and the delivery of more effective CVD prevention programs.International Registered Report Identifier (IRRID)PRR1-10.2196/9017

Development and Validation of the Real-World Progression in Diabetes (RAPIDS) Model.

To develop and validate the first real-world data-based type 2 diabetes progression model (RAPIDS) employing econometric techniques that can study the comparative effects of complex dynamic patterns of glucose-lowering drug use. The US Department of Veterans Affairs (VA) electronic medical record and claims databases were used to identify over 500,000 diabetes patients in 2003 with up to 9-year follow-up. The RAPIDS model contains interdependent first-order Markov processes over quarters for each of the micro- and macrovascular events, hypoglycemia, and death, as well as predictive models for 8 biomarker levels. Model parameters varied by static demographic factors and dynamic factors, such as age, duration of diabetes, 13 possible glucose-lowering treatment combinations, any blood pressure and any cholesterol-lowering medications, and cardiovascular history. To illustrate model capabilities, a simple comparative study was set up to compare observed treatment use patterns to alternate patterns if perfect adherence is assumed following initiating the use of any of these medications. Data were randomly split into 307,288, 105,195, and 105,081 patients to perform estimation, out-of-sample calibration, and validation, respectively. Model predictions in the validation sample closely aligned with the observed longitudinal trajectory of biomarkers and outcomes. Perfect adherence among initiators increased proportion of days covered by only 6 months. Most of this increase came from increased adherence to monotherapies and did not lead to meaningful changes in any of the outcomes over the 9-year period. Future value of increasing medication adherence among VA patients with diabetes may lie among those who never initiate treatment or are late in initiating treatment. The first-of-its-kind real-world data-based model has the potential to carry out many complex comparative-effectiveness research (CER) studies of dynamic glucose-lowering drug regimens.

Prostate cancer survival among statin users after prostatectomy in a Finnish nationwide cohort.

Improved prostate cancer (PCa) survival by statin use has been reported among PCa patients managed with radiation or androgen deprivation therapy (ADT), while results are controversial for men managed surgically. We evaluate the association between cholesterol-lowering medication with initiation of ADT and disease-specific death among PCa cases who underwent radical prostatectomy in Finland between 1995 and 2013. The study cohort included 14 424 men with PCa who underwent radical prostatectomy in Finland between 1995 and 2013. Cases were identified from national hospital discharge registry. Clinical data were amended from patient files of the treating hospitals. Information on co-morbidities, additional radiation- or chemotherapy, and causes of deaths were collected from national registries. Personal-level data on medication use during 1995-2014 were gathered from national prescription database. Registry linkages were carried out using personal identification number. Lipid-lowering drugs were categorized into statins and non-statin drugs. Risk of PCa death and initiation of ADT was analyzed using Cox-regression model with adjustment for age, radiation therapy, chemotherapy, co-morbidities and other drug use. Statin use was analyzed as time-dependent variable. Delayed risk associations were evaluated in lag-time analysis. Compared to non-users the risk of PCa death was significantly lower among statin users before PCa diagnosis (HR 0.70, 95%CIs 0.52-0.95). For statin use after PCa diagnosis the risk was lowered in age-adjusted analysis (HR 0.76 95%CIs 0.62-0.93) but not after multivariable-adjustment. Post-diagnostic statin use was associated with improved PCa-specific survival in 1, 3 and 5 years lag-time analyses. The risk reduction was clearest for statin use initiated 5 years earlier (HR 0.71 95%CIs 0.55-0.92). Use of statins both before and after PCa diagnosis was associated with reduced risk of ADT use (HR 0.72 95%CIs 0.65-0.80 and HR 0.73, 95%CI 0.67-0.80, respectively). The risk of ADT decreased by increasing intensity of statin use before diagnosis. Statin use among surgically treated PCa patients has significant association with decreased risk of starting ADT and PCa death. The risk is lowered especially among men with statin use before PCa diagnosis and in men who used statins at high-dose. Our results are hypothesis generating due to retrospective study design.

Clonal Hematopoiesis in Older Women with Extremely Skewed, Non-Random X-Inactivation Is Associated with Previous Cardiovascular and Cerebrovascular Events

Clonal Hematopoiesis in Older Women with Extremely Skewed, Non-Random X-Inactivation Is Associated with Previous Cardiovascular and Cerebrovascular Events

The Question of a Role for Statins in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in patients over the age of 65 years in industrialized countries. Epidemiologic studies suggest that high dietary fat intake is a risk factor for the development and progression of both vascular and retinal disease. These, and other associations, suggest a hypothesis linking elevated cholesterol and AMD progression. It follows, therefore, that cholesterol-lowering medications, such as statins, may influence the onset and progression of AMD. However, the findings have been inconclusive as to whether statins play a role in AMD. Due to the significant public health implications of a potential inhibitory effect of statins on the onset and progression of AMD, it is important to continually evaluate emerging findings germane to this question.

Disparities in Statin Use in New York City: Implications for Health Reform.

Heart disease is the leading cause of death in the USA, and there is an extensive literature describing disparities in the treatment of the disease. Cholesterol-lowering medications are an effective strategy for reducing the risk of cardiovascular diseases for many patients, but some who are prescribed these medications fail to take them. We examine data from the 2014 New York City Community Health Survey to investigate the factors that influence why patients are not compliant in following the prescribed regimen. We focus on adults age 45 and older who report that they are diagnosed with elevated cholesterol levels and were told by a health professional they needed to take cholesterol-lowering medication. We find that evident disparities: individuals with low incomes, those who rely on emergency departments for their healthcare, have not received medical care within the past year, are depressed, and identify as black non-Hispanic and Hispanic are less likely to adhere to a cholesterol-lowering medication program. Although Medicare beneficiaries are less likely to take cholesterol-lowering medication than those with private insurance, those who were on Medicaid or were uninsured did not report lower rates of adherence.

Primary Prevention Using Cholesterol-Lowering Medications in Patients Meeting New Treatment Guidelines: A Retrospective Cohort Analysis.

The American College of Cardiology and American Heart Association (ACC/AHA) issued new cholesterol treatment guidelines in 2013. Two of the groups designated for primary prevention were analyzed: patients with a low-density lipoprotein cholesterol (LDL-C) level ≥ 190 mg per dL and diabetic patients aged 40-75 years. To estimate the effects of primary prevention as specified in the 2013 guidelines on cardiovascular event risk and cost. Primary prevention patients were identified using laboratory and diagnostic data for Humana members from 2007 to 2013. Potential study patients were classified into 3 risk groups: elevated LDL-C, diabetes, and elevated LDL-C and diabetes. Patients receiving cholesterol-lowering medications before their index date were excluded. Eligible patients were divided into 2 treatment groups: (1) primary prevention patients who initiated treatment before experiencing any cardiovascular disease (CVD)-related event, and (2) patients who either did not initiate treatment until after experiencing a CVD event or never initiated treatment. The associations between initiating cholesterol-lowering medications for primary prevention and the risk for acute myocardial infarction, stroke, coronary angioplasty, or coronary artery bypass graft surgery were estimated using Cox proportional hazards models. The effect of primary prevention on health care costs was estimated using generalized linear models. 91,066 patients met study selection criteria. Primary prevention rates were the lowest in diabetic patients (35%), who were newly designated for treatment in the 2013 guidelines. Primary prevention rates were higher for patients designated for treatment under earlier guidelines: 65% for patients with elevated LDL-C and 78% for the combined LDL-C and diabetes group. Primary prevention treatment was associated with significant reductions in cardiovascular event risk (up to 37%) and lower total all-cause costs (by $673) in the first post-index year. Initiating cholesterol-lowering medications for primary prevention, as specified in the ACC/AHA 2013 guidelines, for patients with high LDL-C and diabetes is associated with reduced CVD event risks and lower health care costs. No outside funding supported this study. Han received fellowship support from the Pharmaceutical Research and Manufacturers Association Foundation (PhRMA) during the conduct of this study. Dougherty is employed by PhRMA. The authors have nothing to disclose.

Relationship of statins and other cholesterol-lowering medications and risk of amyotrophic lateral sclerosis in the US elderly

Objective: Statins are commonly prescribed drugs that have been inconsistently associated with amyotrophic lateral sclerosis (ALS) risk. We examined associations between ALS risk and overall statin use, statin categories based on lipophilicity and other cholesterol-lowering medications, in Medicare beneficiaries.Methods: In this nation-wide population-based case-control study, 10,450 Medicare participants (ages 66–89 years) diagnosed with ALS, using Medicare Parts A and B claims, between 1 January 2008 and 31 December 2014, were frequency-matched to 104,500 controls on age, sex, and selection year. Odds ratios (ORs) for the association between statins and ALS were estimated using logistic regression models. Covariates included dyslipidemia, other comorbidities, age, sex, race, proxies for smoking and obesity, Medicare use, and indicators of socioeconomic status. Statin use derived from Medicare Part D claims. Non–statin cholesterol–lowering drugs were evaluated as comparison drugs.Results: ALS risk was reduced with statin use (OR = 0.87 (95% confidence interval (CI) = 0.83–0.91)). While risk was unrelated to three cholesterol-lowering medications (nitrates, bile acid sequestrants, and ezetimibe), it was associated with fibrates (OR = 0.88 (95% CI = 0.80–0.97)). Risk for lipophilic statins was slightly lower than for other statins. ALS risk was lower in all statin categories for dyslipidemic individuals, but only lipophilic statins were associated with lower risk in non-dyslipidemic individuals and demonstrated an inverse trend with duration.Conclusions: Our findings suggest that statins are associated with lower ALS risk and offer new evidence that fibrates may be related to lower risk. However, we were unable to fully adjust for smoking and body mass index.

Korea hypertension fact sheet 2018

BackgroundThe Korea Hypertension Fact Sheet 2018 aims to overview the magnitude and management status of hypertension, and their trends in Korea.MethodsThe Hypertension Epidemiology Research Group analyzed the 1998–2016 Korea National Health and Nutrition Examination Survey data and the 2002–2016 Korea National Health Insurance Big Data.ResultsThe population average of systolic/diastolic blood pressure was 118/77 mmHg among Korean adults (age 30+) in 2016, showing little change in recent 10 years. However, the number of people with hypertension increased steadily, exceeding 11 million. The number of people diagnosed with hypertension increased from 3 million in 2002 to 8.9 million in 2016. The number of people using antihypertensive medication increased from 2.5 million in 2002 to 8.2 million in 2016. However, only 5.7 million people are being treated constantly. Hypertension awareness, treatment, and control rates increased fast until 2007, but showed a plateau thereafter. More than half of the young hypertensive patients (30–49 years) did not know about and treat for their hypertension. Among patients prescribed antihypertensive medications, 45% was elderly people over the age of 65 years, 57% used anti-diabetic or cholesterol-lowering medications, and 60% were prescribed two or more class of antihypertensive medications simultaneously.ConclusionsIn Korea, the level of hypertension management has considerably improved over the last 20 years. In order to achieve further improvement in hypertension management status, we need to find the vulnerable subgroups and develop subgroup-specific intervention strategies. It is also becoming more important to manage hypertensive patients at older age and those with concurrent chronic diseases.

Effects of medication, treatment, and behavioral beliefs on intentions to take medication in patients with familial hypercholesterolemia

Background and aimsAlthough familial hypercholesterolemia (FH) can be effectively managed using cholesterol-lowering medication, patients often fall short of complete treatment adherence. Identifying the psychological factors associated with self-regulation of FH medication is important to inform interventions to maximize adherence. The aim of the present study was to test an integrated psychological model in predicting FH patients' intentions to take medication. MethodsFH patients attending clinics in seven countries were invited to participate in a cross-sectional survey study. Consenting patients (N = 551) completed self-report measures of generalized beliefs about medication overuse and harms, beliefs in treatment effectiveness, specific beliefs about taking medication (attitudes, subjective norms, perceived behavioral control), and intentions to take medication. Participants also completed measures of demographic variables (age, gender, education level, income, cardiovascular disease status). Data were analysed using path analysis controlling for country and demographic variables. ResultsAttitudes (β = .331, p<0.001), subjective norms (β = .121, p=0.009), and beliefs about medication overuse (β = −.160, p<0.001) were significant predictors of intentions to take medication. Treatment beliefs predicted intentions indirectly (β = .088, p<0.001) through attitudes and subjective norms. There was also an indirect effect of beliefs about medication overuse on intentions (β = −.045, p=0.056), but the effect was small compared with the direct effect. ConclusionsThe findings indicate the importance among FH patients of specific beliefs about taking medication and generalized beliefs about medication overuse and treatment in predicting medication intentions. When managing patients, clinicians should emphasize the efficacy of taking cholesterol-lowering drugs and the importance of treatment outcomes, and allay concerns about medication overuse.

Role of simvastatin in tumor lymphangiogenesis and lymph node metastasis.

Lymphangiogenesis plays a crucial role in promoting cancer metastasis to sentinel lymph nodes (LNs) and beyond. Increasing data have shown that simvastatin, a cholesterol-lowering medication for the prevention of cardiovascular diseases, is involved in tumor growth and dissemination, and endothelial functions. This study aimed to investigate the potential effect of simvastatin on lymphatic formation and LN metastasis. Tumor models were established by subcutaneous injection of B16-F10 melanoma cells into mouse hind footpads. Simvastatin was administered (0.2µg/g, intraperitoneal injection, IP) every other day for a total of eight times. Tissue samples were removed and examined by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) techniques. The lymphatics of LN, skin, liver, and lung exhibited morphological changes, and LN weight and metastatic area of the tumor group treated with simvastatin was lower than that of the untreated tumor group. Analysis of lymphatic size, area fraction, and lymphatic vessel density showed tissue specificity and variation to melanoma carcinogenesis in the simvastatin-treated group compared with the untreated group. In addition, LNs and cutaneous tissues showed altered expression of lymphangiogenic factors and inflammatory cytokines such as VEGF-A/-C/-D and TNF-α. These findings indicated that simvastatin may modify lymphangiogenesis and tumor progression in malignant melanoma.

Engineering Saccharomyces cerevisiae for production of simvastatin

Simvastatin is a semisynthetic cholesterol-lowering medication and one of the top-selling statins in the world. Currently, industrial production of simvastatin acid (SVA) is a multistep process starting from the natural product lovastatin. For this reason, there is significant interest in direct production of simvastatin from a microbial host. In this study, six heterologous biosynthetic genes were introduced into Saccharomyces cerevisiae and the acyl-donor dimethylbutyryl-S-methyl mercaptopropionate (DMB-SMMP) was added, resulting in initial production of 0.5 mg/L SVA. Switching the yeast strain from JHY686 to BJ5464-NpgA increased total polyketide production to over 60 mg/L and conversion from dihydromonacolin L acid to monacolin J acid (MJA) was increased from 60% to 90% by tuning the copy number of the P450 lovA. Increasing the media pH to 8.7 led to a further 10-fold increase in SVA production. Optimized chemical lysis of the cell walls in situ after maximum MJA production led to 55 mg/L SVA titer, representing nearly complete conversion from MJA and a 110-fold increase in titer from the initial SVA production strain. The yeast strains developed in this work can be used as an alternative production method for SVA, and the strategies employed can be broadly applied for heterologous production of other fungal polyketides and semisynthetic compounds in yeast.

Hair dyes in pregnant women; is it safe?

Statins (3-hydroxy-3 methyl-glutaryl coenzyme-A reductase inhibitors) are the most commonly prescribed cholesterol-lowering medications due to their efficacy in reducing cardiovascular mortality and morbidities, tolerability, and safety profiles. Based on pathophysiologic similarities between cardiovascular disease and preeclampsia, a common and dangerous complication of pregnancy, there is an increasing interest in studying this class of medications during pregnancy to prevent and/or treat preeclampsia. Undergoing such a study, which entails the use of a pregnancy class X medication for an off-label indication in pregnancy, requires intensive multidisciplinary involvement of a group of experts in basic and clinical pharmacology, research methods, pregnancy physiology and maternal–fetal medicine, as well as U.S. Food and Drug Administration (FDA) regulatory guidelines and practice. Issues of potential fetal risk, altered maternal–fetal pharmacokinetics and pharmacodynamics, and regulatory challenges are real, and must be carefully considered in the process of research in this arena.

Optimising treatment of hyperlipidaemia: Quantitative evaluation of UK, USA and European guidelines taking account of both LDL cholesterol levels and cardiovascular disease risk

Background and aimsGuidelines for cholesterol-lowering medication either advocate fixed dose statin treatment without low density lipoprotein (LDL) cholesterol targets or treatment aimed at LDL cholesterol goals. The decrease in LDL cholesterol concentration determines the reduction in atherosclerotic cardiovascular disease (CVD) risk. MethodsAs indices of the effectiveness of reductions in LDL cholesterol concentration achieved by the various guidelines, the number of CVD events prevented in 100 people during 10 years of treatment (N100) and the number of people, who must be treated for 10 years to prevent one CVD event (NNT), were calculated taking into account both CVD risk and pretreatment LDL cholesterol concentration. That our method of calculating NNT and N100, could be extended to statin regimens of different intensity or of statin combined with adjunctive cholesterol-lowering medication was demonstrated by meta-analysis. ResultsReductions in LDL-cholesterol concentration are determined by the choice and dose of medication and by the pre-treatment LDL-cholesterol concentration. At similar CVD risk, whatever cholesterol-lowering strategy is adopted, people with higher pre-treatment LDL cholesterol benefit more than those with lower levels. Fixed dose statin regimens are less effective than target LDL cholesterol levels of 1.8 or 1.4 mmol/l when pre-treatment LDL-cholesterol levels exceed 4 mmol/l. However, fixed dose statin is more effective in people with lower initial LDL cholesterol. The predicted NNT and N100 were closely related to the observed reduction in CVD risk in our meta-analysis. ConclusionsIn hypercholesterolaemia, aiming for LDL cholesterol targets with statin dose titration (and when necessary adjunctive medication) is essential to optimise benefit.

Association of APOL1 With Heart Failure With Preserved Ejection Fraction in Postmenopausal African American Women

APOL1 genotypes are associated with kidney diseases in African American individuals and may influence cardiovascular disease and mortality risk, but findings have been inconsistent. To discern whether high-risk APOL1 genotypes are associated with cardiovascular disease and stroke in postmenopausal African American women, who are at high risk for these outcomes. The Women's Health Initiative is a prospective cohort that enrolled 161 838 postmenopausal women into clinical trials and an observational study between 1993 and 1998. This study includes 11 137 African American women participants who had a clinical event from enrollment to June 2014. Data analyses were completed from January 2017 to August 2017. The variants of APOL1 were genotyped or imputed from whole-exome sequencing. Incident coronary heart disease, stroke and heart failure subtypes, and overall and cause-specific mortality were adjudicated from hospital records and death certificates. Estimated incidence rates were determined for each outcome and hazard ratios (HR) and 95% CIs for the associations of APOL1 groups with outcomes. The mean (SD) age of participants was 61.7 (7.1) years. Carriers of high-risk APOL1 variants (n = 1370; 12.3%) had higher prevalence of hypertension, use of cholesterol-lowering medications, and reduced estimated glomerular filtration rate (eGFR). After a mean (SD) of 11.0 (3.6) years, carriers of high-risk APOL1 variants had a higher incidence rate of hospitalized heart failure with preserved ejection fraction (HFpEF) than low-risk carriers did but showed no differences for other outcomes. In adjusted models, there was a significant 58% increased hazard of hospitalized HFpEF (HR, 1.58 [95% CI, 1.03-2.41]) among carriers of high-risk APOL1 variants compared with carriers of low-risk APOL1 variants. The association with HFpEF was attenuated (HR = 1.50 [95% CI, 0.98-2.30]) and no longer significant when adjusting for baseline eGFR. Status as a carrier of a high-risk APOL1 genotype was associated with HFpEF hospitalization among postmenopausal women, which is partly accounted for by baseline kidney function. These findings do not support an association of high-risk APOL1 genotypes with coronary heart disease, stroke, or mortality in postmenopausal African American women.

Abstract 5257: Prevalence and trends of obesity and metabolic syndrome among U.S. adults diagnosed with cancer, NHANES 1999-2014

Abstract Background: The prevalence of obesity and Metabolic syndrome (MetS) in the general population has been documented extensively. While obesity and MetS are associated with cancer risk and may persist after diagnosis, the prevalence and the secular trends of obesity and MetS among cancer survivors has not been examined in a nationally representative cohort. Objective: To compare adults diagnosed with cancer and those without cancer on the prevalence of obesity and MetS in 2013-2014, and on the time trends over the past years from 1999 through 2014. Methods: A sample of 39,608 adults, aged 20+ who participated in National Health and Nutrition Examination Survey (NHANES) surveys from 1999-2014 were included. Of those surveyed, 2,811 subjects had been diagnosed with non-skin cancers, and 1,770 with obesity-linked cancers (colorectal, liver, kidney, esophageal, stomach, pancreatic, gallbladder, breast, endometrial, ovarian and prostate). MetS was defined as having at least three of the following five factors: elevated levels of (1) triglyceride, (2) systolic or diastolic blood pressure, or use of anti-hypertensive medication, (3) blood glucose or self-reported diabetes or use of insulin, (4) enlarged waist circumference and (5) lower levels of high-density lipoprotein (HDL) cholesterol or use of cholesterol lowering medication. Results: In 2013-2014, the prevalence of obesity was 41.1%, 40.5% and 37.8% among adults diagnosed with obesity-linked cancers, total-cancer, and no cancer diagnosis, respectively. The prevalence of obesity have significantly increased over the last 16 years for all three groups. Relative to adults without a cancer diagnosis, the 16-year increase in obesity prevalence was significantly higher for those with obesity-linked cancers (p=0.019), but not with total cancer (p=0.35). In relation to MetS, the 2013-2014 prevalence was significantly higher among adults with obesity-linked cancers (52.7%) and total cancer (50.3%) compared to adults without cancer (29.2%). Over the 16-year period from 1999-2014, the prevalence of MetS has increased among adults with obesity-linked cancers (p=0.008), total cancer (p=&amp;lt;.0001), and those without a cancer diagnosis (p=0.005), respectively. Compared to the adults without a cancer diagnosis, the prevalence of MetS over the years has significantly increased among adults with obesity-linked cancers (p=0.004) and total cancer (p=0.05) were significantly higher. Conclusion: U.S. adults diagnosed with obesity-linked cancers had a higher prevalence of obesity and MetS, and the prevalence have significantly increased over the last 16 years, compared to those without a cancer diagnosis. The findings of this study underscore the urgent need for clinicians and public health workers to recognize and address cardiometabolic health problems among cancer survivors. Citation Format: Wambui Grace Gathirua-Mwangi. Prevalence and trends of obesity and metabolic syndrome among U.S. adults diagnosed with cancer, NHANES 1999-2014 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5257.

Rationale and design of a cluster randomized trial of a multifaceted intervention in people with hypertension: The Heart Outcomes Prevention and Evaluation 4 (HOPE-4) Study

BackgroundCardiovascular disease is the leading cause of death throughout the world, with the majority of deaths occurring in low- and middle-income countries. Despite clear evidence for the benefits of blood pressure reduction and availability of safe and low-cost medications, most individuals are either unaware of their condition or not adequately treated. ObjectiveThe primary objective of this study is to evaluate whether a community-based, multifaceted intervention package primarily provided by nonphysician health workers can improve long-term cardiovascular risk in people with hypertension by addressing identified barriers at the patient, health care provider, and health system levels. Methods/designHOPE-4 is a community-based, parallel-group, cluster randomized controlled trial involving 30 communities (1,376 participants) in Colombia and Malaysia. Participants ≥50 years old and with newly diagnosed or poorly controlled hypertension were included. Communities were randomized to usual care or to a multifaceted intervention package that entails (1) detection, treatment, and control of cardiovascular risk factors by nonphysician health workers in the community, who use tablet-based simplified management algorithms, decision support, and counseling programs; (2) free dispensation of combination antihypertensive and cholesterol-lowering medications, supervised by local physicians; and (3) support from a participant-nominated treatment supporter (either a friend or family member). The primary outcome is the change in Framingham Risk Score after 12 months between the intervention and control communities. Secondary outcomes including change in blood pressure, lipid levels, and Interheart Risk Score will be evaluated. SignificanceIf successful, the study could serve as a model to develop low-cost, effective, and scalable strategies to reduce cardiovascular risk in people with hypertension.

CV2 - Secondary Prevention Using Cholesterol-Lowering Medications in Patients Meeting New Treatment Guidelines: A Retrospective Cohort Analysis

The risk groups designated for cardiovascular disease (CVD) secondary prevention were updated in the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines. This study estimated the impact of initiating secondary prevention using cholesterol-lowering medications on the risk of CVD-related hospitalization and on healthcare costs in patients qualifying for secondary prevention under the ACC/AHA Guidelines of 2013. The high-risk patients qualifying for secondary prevention under the 2013 guidelines were identified using diagnostic and hospitalization data for Humana [2007-2013]. Patients with an atherosclerotic cardiovascular event (ASCVD) were assumed eligible for secondary prevention. Patients with prior use of cholesterol-lowering medications before their index ASCVD date were then excluded. Patients were classified into ASCVD risk groups based on the CVD events that defined their index date. Patients were further designated into two treatment groups: [1] secondary prevention patients who initiated treatment before experiencing a second CVD-related hospitalization and [2] patients who did not initiate treatment until after experiencing a second CVD admission or who never initiated treatment. The impact of secondary prevention on the risk for cardiovascular hospitalization was estimated using Cox proportional hazards models. The impact of secondary prevention on healthcare costs was estimated using generalized linear models [GLM]. 208,402 patients met eligibility requirements and all other study inclusion criteria. Only 21% of eligible patients initiated secondary prevention during 2007-2013. Initiating secondary prevention using a cholesterol-lowering treatment decreased the likelihood of having a second cardiovascular-related hospitalization by 47%. Secondary prevention increased prescription drug costs per patient in the first year by $222, but the impact on medical service costs was not significant. Few patients designated for secondary prevention under the 2013 guidelines initiated treatment in the pre-guideline period [21%]. Patients who initiated secondary prevention experienced significantly reduced risks of a second CVD-related hospitalization.

PCV84 - Primary Prevention Using Cholesterol-Lowering Medications in Patients Meeting New Treatment Guidelines: A Retrospective Cohort Analysis

The 2013 American College of Cardiology/American Heart Association (ACC /AHA) guidelines expanded primary prevention using cholesterol-lowering therapy to all diabetic patients. Our research documents the potential for expanded primary prevention eligibility to improve cardiovascular outcomes and reduce cost. Patients meeting 2013 guidelines for primary prevention were identified using laboratory and diagnostic data from Humana [2007-2013]. Patients were classified into three risk groups: LDL levels ≥ 190 mg/dL, patients with diabetes (aged 40 to 75), and patients with both elevated LDL-C and diabetes. Patients with no pre-classification cholesterol treatment were then selected and divided in two treatment groups: [1] patients who initiated treatment before experiencing any cardiovascular disease-related event and [2] patients who did not initiate treatment until after experiencing a CVD event (or who never initiated treatment). Clinical outcomes measured were the time to four separate events: AMI, stroke, coronary angioplasty, coronary artery bypass graft surgery (CABG). Costs were measured over the first year following a risk classification. Clinical outcomes were analyzed using Cox proportional hazards models. Costs were analyzed using generalized linear models [GLM]. 91,066 patients were selected according to ACC/AHA guidelines and met study selection criteria. Primary prevention treatment rates were the lowest in diabetic patients [35%], most of whom were newly designated for treatment in the 2013 guidelines. Primary prevention treatment rates were higher for patients identified in earlier guidelines: 65% for patients with elevated LDL and 78% for the combined LDL+diabetes group. Primary prevention was associated with significant reductions in cardiovascular event risk (up to 37%) and lower total all-cause costs in the first post-index year (by $673). Primary prevention using cholesterol-lowering medications, as specified in the new 2013 guidelines for patients with high-LDL or/and diabetes, is projected here to both reduce CVD event risk and lower healthcare costs.

Nonadherence to statins: individualized intervention strategies outside the pill box.

Poor adherence to statin therapy is linked to significantly increased risk of cardiovascular events and death. Unfortunately, adherence to statins is far from optimal. This is an alarming concern for patients prescribed potentially life-saving cholesterol-lowering medication, especially for those at high risk of cardiovascular events. Research on statin adherence has only recently garnered broader attention; hence, major reasons unique to adherence to statin therapy need to be identified as well as suggestions for countermeasures. An integrated approach to minimizing barriers and enhancing facilitation at the levels of the patient, provider, and health system can help address adherence issues. Health care professionals including physicians, pharmacists, and nurses have an obligation to improve patient adherence, as routine care. In order to achieve sustained results, a multifaceted approach is indispensable.