Producing personalized statin treatment plans to optimize clinical outcomes using big data and machine learning.

Almost half of Americans 65 years of age and older take statins, which are highly effective in lowering low-density lipoprotein cholesterol, preventing atherosclerotic cardiovascular disease (ASCVD), and reducing all-cause mortality. Unfortunately, ∼50% of patients prescribed statins do not obtain these critical benefits because they discontinue use within one year of treatment initiation. Therefore, statin discontinuation has been identified as a major public health concern due to the increased morbidity, mortality, and healthcare costs associated with ASCVD. In clinical practice, statin-associated symptoms (SAS) often result in dose reduction or discontinuation of these life-saving medications. Currently, physician decision-making in statin prescribing typically relies on only a few patient data elements. Physicians then employ reactive strategies to manage SAS concerns after they manifest (e.g., offering an alternative statin treatment plan or a statin holiday). A preferred approach would be a proactive strategy to identify the optimal treatment plan (statin agent + dosage) to prevent/minimize SAS and statin discontinuation risks for a particular individual prior to initiating treatment. Given that using a single patient's data to identify the optimal statin regimen is inadequate to ensure that the harms of statin use are minimized, alternative tactics must be used to address this problem. In this proof-of-concept study, we explore the use of a machine-learning personalized statin treatment plan (PSTP) platform to assess the numerous statin treatment plans available and identify the optimal treatment plan to prevent/minimize harms (SAS and statin discontinuation) for an individual. Our study leveraged de-identified administrative insurance claims data from the OptumLabs® Data Warehouse, which includes medical and pharmacy claims, laboratory results, and enrollment records for more than 130 million commercial and Medicare Advantage (MA) enrollees, to successfully develop the PSTP platform. In this study, we found three results: (1) the PSTP platform recommends statin prescription with significantly lower risks of SAS and discontinuation compared with standard-practice, (2) because machine learning can consider many more dimensions of data, the performance of the proactive prescription strategy with machine-learning support is better, especially the artificial neural network approach, and (3) we demonstrate a method of incorporating optimization constraints for individualized patient-centered medicine and shared decision making. However, more research into its clinical use is needed. These promising results show the feasibility of using machine learning and big data approaches to produce personalized healthcare treatment plans and support the precision-health agenda.

Self-controlled assessment of thromboembolic event (TEE) risk following intravenous immune globulin (IGIV) in the U.S. (2006-2012).

Since 2013, the U.S. Food and Drug administration (FDA) has required that intravenous immune globulin (IGIV) products carry a boxed warning concerning the risk of thromboembolic events (TEEs). This study assessed the incidence of TEEs attributable to IGIV in a large population-based cohort. A self-controlled risk interval design was used to quantify the transient increase in TEE risk during the risk interval (days 0-2 and 0-13 following IGIV for arterial and venous TEEs, respectively) relative to a later control interval (days 14-27 following IGIV). Potential IGIV-exposed TEE cases from 2006 to 2012 were identified from the FDA-sponsored Sentinel Distributed Database and confirmed through medical record review. Inpatient IGIV exposures were not included in the venous TEE analysis due to concerns about time-varying confounding. 19,069 new users of IGIV who received 93,555 treatment episodes were included. Charts were retrieved for 62% and 70% of potential venous and arterial cases, respectively. There was a transient increase in the risk of arterial TEEs during days 0-2 following IGIV treatment (RR = 4.69; 95% CI 1.87, 11.90; absolute increase in risk = 8.86 events per 10,000 patients, 95% CI 3.25, 14.6), but no significant increase in venous TEE risk during days 0-13 following outpatient IGIV treatments (RR = 1.07, 95% CI 0.34, 3.48). Our results suggest there is a small increase in the absolute risk of arterial TEEs following IGIV. However, lower-than-expected chart retrieval rates and the possibility of time-varying confounding mean that our results should be interpreted cautiously. Continued pharmacovigilance efforts are warranted.

Challenges and Opportunities for the Prevention and Treatment of Cardiovascular Disease Among Young Adults: Report From a National Heart, Lung, and Blood Institute Working Group.

Improvements in cardiovascular disease (CVD) rates among young adults in the past 2 decades have been offset by increasing racial/ethnic and gender disparities, persistence of unhealthy lifestyle habits, overweight and obesity, and other CVD risk factors. To enhance the promotion of cardiovascular health among young adults 18 to 39 years old, the medical and broader public health community must understand the biological, interpersonal, and behavioral features of this life stage. Therefore, the National Heart, Lung, and Blood Institute, with support from the Office of Behavioral and Social Science Research, convened a 2-day workshop in Bethesda, Maryland, in September 2017 to identify research challenges and opportunities related to the cardiovascular health of young adults. The current generation of young adults live in an environment undergoing substantial economic, social, and technological transformations, differentiating them from prior research cohorts of young adults. Although the accumulation of clinical and behavioral risk factors for CVD begins early in life, and research suggests early risk is an important determinant of future events, few trials have studied prevention and treatment of CVD in participants <40 years old. Building an evidence base for CVD prevention in this population will require the engagement of young adults, who are often disconnected from the healthcare system and may not prioritize long-term health. These changes demand a repositioning of existing evidence-based treatments to accommodate new sociotechnical contexts. In this article, the authors review the recent literature and current research opportunities to advance the cardiovascular health of today's young adults.

Enhancing the value of PCSK9 monoclonal antibodies by identifying patients most likely to benefit. A consensus statement from the National Lipid Association.

Acquisition costs and cost-effectiveness have limited access and recommendations to use proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibiting monoclonal antibodies (mAbs). Recently, prices were reduced by 60% for alirocumab and evolocumab. This statement systematically reviewed subgroup analyses from statin and PCSK9 mAb trials to identify higher risk groups for which PCSK9 mAbs at the new price could be considered a reasonable (

Practice-level variation in statin use and low-density lipoprotein cholesterol control in the United States: Results from the Patient and Provider Assessment of Lipid Management (PALM) registry.

BACKGROUND: Adherence to guideline-recommended statin recommendations in the United States is suboptimal. Patients' likelihood to be treated according to guidelines may vary by the practice in which they are treated. METHODS: Variation in the use of statin therapy in 5445 patients, with known or at high risk for atherosclerotic cardiovascular disease (ASCVD) and meeting a statin treatment indication, was examined across 74 US Patient and Provider Assessment of Lipid Management (PALM) Registry clinics. Multivariable generalized linear mixed modeling was used to determine the median odds ratio (MOR) for statin use and 2013 American College of Cardiology/American Heart Association guideline-recommended statin intensity by practice. MOR quantifies between-practice variation by comparing the odds of receiving guideline-recommended statin treatment in a patient from a randomly selected practice with a similar patient from another random practice. Risk-adjusted low-density lipoprotein cholesterol (LDL-C) control (<100 and <70 mg/dL) was compared among practice tertiles based on percentage of eligible patients receiving recommended statin intensity. RESULTS: Among 74 practices (43.2% cardiology) comprised of 300 healthcare providers enrolling 5445 patients (56.2% with ASCVD), statin use at the guideline-recommended intensity at practices varied widely (12.7-71.4%; adjusted MOR 1.45, 95% confidence interval [CI] 1.35-1.64). Results were consistent when evaluated for any statin use overall (adjusted MOR 1.75, 95% CI 1.48-1.99) and when stratified by primary versus secondary prevention patients. Relative to practices with lowest or mid-tertile statin use of statins, highest tertile clinics were more frequently cardiology practices (68.0% vs 48.0% vs 12.5%, P < .001). Compared with lowest tertile clinics, patients at highest tertile clinics were more likely to achieve LDL-C <70 mg/dL (adjusted odds ratio [OR] 1.49, 95% CI 1.08-2.04) and <100 mg/dL (adjusted OR 1.78, 95% CI 1.41-2.25). CONCLUSIONS: US clinics varied widely in their adherence to guideline recommendations for statin therapy, which contributed to significant differences in LDL-C levels.

Incidence of and Risk Factors for Severe Adverse Events in Elderly Patients Taking Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers after an Acute Myocardial Infarction.

STUDY OBJECTIVE: To assess the incidence of and risk factors associated with severe adverse events in elderly patients who used angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) after an acute myocardial infarction (AMI). DESIGN: Retrospective cohort study. DATA SOURCES: Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse (Medicare service claims database), American Community Survey of the U.S. Census Bureau, and Multum Lexicon Drug database. PATIENTS: A total of 101,588 eligible Medicare fee-for-service beneficiaries 66 years or older, who were hospitalized for AMI between January 1, 2008, and December 31, 2009, and used ACEIs or ARBs within 30 days after discharge. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were hospitalizations for acute renal failure (ARF) and hyperkalemia. The secondary outcome was discontinuation or suspension of ACEI/ARB therapy after a visit to a health care provider. The primary risk factors of interest were age, sex, race/ethnicity, and chronic kidney disease (CKD). Cumulative incidence curves and multivariable Fine-Gray proportional hazards models with 95% confidence intervals (CIs) were used with death as a competing risk in both intention-to-treat (ITT) and as-treated (AT) analyses. In the study cohort, 2.8% experienced ARF, 0.5% experienced hyperkalemia, and 63.7% discontinued ACEI/ARB therapy within 1 year after hospital discharge. Approximately half of the incidence of ARF and hyperkalemia occurred within 6 months after hospital discharge, but the cumulative incidence increased after 6 months. Patients older than 85 years had a higher rate of ARF (ITT hazard ratio [HR] 1.15, 95% CI 1.04-1.28) and hyperkalemia (ITT HR 1.33, 95% CI 1.05-1.68) compared with those aged 65-74 years. Patients with baseline CKD had higher rates of ARF (ITT HR 1.61, 95% CI 1.42-1.82), hyperkalemia (ITT HR 1.41, 95% CI 1.11-1.77), and ACEI/ARB therapy discontinuation or suspension (ITT HR 1.05, 95% CI 1.02-1.09). CONCLUSION: We found a low incidence of ARF and hyperkalemia in elderly patients treated with ACEIs or ARBs after AMI hospitalization. However, a high rate of treatment discontinuation might prevent a higher rate of occurrence of these events. Long-term careful monitoring of severe adverse events and timely discontinuation of ACEIs or ARBs among elderly patients with advancing age and CKD after an AMI is warranted in clinical practice.

Lipid management in contemporary community practice: Results from the Provider Assessment of Lipid Management (PALM) Registry.

BACKGROUND: The latest cholesterol guidelines have shifted focus from achieving low-density lipoprotein cholesterol (LDL-C) targets toward statin use and intensity guided by atherosclerotic cardiovascular disease (ASCVD) risk. METHODS: Statin use and intensity were evaluated in 5,905 statin-eligible primary or secondary prevention patients from 138 PALM Registry practices. RESULTS: Overall, 74.7% of eligible adults were on statins; only 42.4% were on guideline-recommended intensity. Relative to primary prevention patients, ASCVD patients were more likely to be on a statin (83.6% vs 63.4%, P<.0001) and guideline-recommended intensity (47.3% vs 36.0%, P<.0001). Men were more likely than women to be prescribed recommended intensity for primary (odds ratio [OR] 1.87, 95% CI 1.49-2.34) and secondary (OR 1.47, 95% CI 1.26-1.70) prevention. In primary prevention, increasing age, diabetes, obesity, hypertension, and lower 10-year ASCVD risk were associated with increased odds of receiving recommended intensity. Among ASCVD patients, those with coronary artery disease were more likely to be on recommended intensity than cerebrovascular or peripheral vascular disease patients (OR 1.71, 95% CI 1.41-2.09), as were those seen by cardiologists (OR 1.43, 95% CI 1.12-1.83). Median LDL-C levels were highest among patients not on statins (124.0 mg/dL) and slightly higher among those on lower-than-recommended intensity compared with recommended-therapy recipients (88.0 and 84.0 mg/dL, respectively; P≤.0001). CONCLUSIONS: In routine contemporary practice, 1 in 4 guideline-eligible patients was not on a statin; less than half were on the recommended statin intensity. Untreated and undertreated patients had significantly higher LDL-C levels than those receiving guideline-directed statin treatment.

Changes in Statin Adherence Following an Acute Myocardial Infarction Among Older Adults: Patient Predictors and the Association With Follow-Up With Primary Care Providers and/or Cardiologists.

BACKGROUND: Hospitalizations for acute myocardial infarctions (AMIs) are associated with changes in statin adherence. It is unclear to what extent adherence changes, which patients are likely to change, and how post-discharge follow-up is associated with statin adherence change. METHODS AND RESULTS: This retrospective study used Medicare data for all fee-for-service beneficiaries 66 years and older with an AMI hospitalization in 2008-2010 and statin use before their index AMI. Multivariable multinomial logistic regression models (odds ratio [OR] and 99% confidence interval [CI]) were applied to assess associations between both patient characteristics and follow-up with a primary care provider and/or cardiologist with the outcome of statin adherence change (increase or decrease) from the 6-month pre- to 6-month post-AMI periods. Of 113 296 patients, 64.0% had no change in adherence, while 19.7% had increased and 16.3% had decreased adherence after AMI hospitalization. Black and Hispanic patients were more likely to have either increased or decreased adherence than white patients. Patients who required coronary artery bypass graft surgery (OR, 1.34; 99% CI, 1.21-1.49) or percutaneous transluminal coronary angioplasty/stent procedure (OR, 1.25; 99% CI, 1.17-1.32) during their index hospitalization were more likely to have increased adherence. Follow-up with a primary care provider was only mildly associated with increased adherence (OR, 1.08; 99% CI, 1.00-1.16), while follow-up with a cardiologist (OR, 1.15; 99% CI, 1.05-1.25) or both provider types (OR, 1.21; 99% CI, 1.12-1.30) had stronger associations with increased adherence. CONCLUSIONS: Post-AMI changes in statin adherence varied by patient characteristics, and improved adherence was associated with post-discharge follow-up care, particularly with a cardiologist or both a primary care provider and a cardiologist.

Adherence Tradeoff to Multiple Preventive Therapies and All-Cause Mortality After Acute Myocardial Infarction.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARB), beta-blockers and statins are recommended after acute myocardial infarction (AMI). Patients may adhere to some, but not all, therapies. OBJECTIVES: The authors investigated the effect of tradeoffs in adherence to ACE inhibitors/ARBs, beta-blockers, and statins on survival among older people after AMI. METHODS: The authors identified 90,869 Medicare beneficiaries ≥65 years of age who had prescriptions for ACE inhibitors/ARBs, beta-blockers, and statins, and survived ≥180 days after AMI hospitalization in 2008 to 2010. Adherence was measured by proportion of days covered (PDC) during 180 days following hospital discharge. Mortality follow-up extended up to 18 months after this period. The authors used Cox proportional hazards models to estimate hazard ratios of mortality for groups adherent to 2, 1, or none of the therapies versus group adherent to all 3 therapies. RESULTS: Only 49% of the patients adhered (PDC ≥80%) to all 3 therapies. Compared with being adherent to all 3 therapies, multivariable-adjusted hazard ratios (95% confidence intervals [CIs]) for mortality were 1.12 (95% CI: 1.04 to 1.21) for being adherent to ACE inhibitors/ARBs and beta-blockers only, 0.98 (95% CI: 0.91 to 1.07) for ACEI/ARBs and statins only, 1.17 (95% CI: 1.10 to 1.25) beta-blockers and statins only, 1.19 (95% CI: 1.07 to 1.32) for ACE inhibitors/ARBs only, 1.32 (95% CI: 1.21 to 1.44) for beta-blockers only, 1.26 (95% CI: 1.15 to 1.38) statins only, and 1.65 (95% CI: 1.54 to 1.76) for being nonadherent (PDC <80%) to all 3 therapies. CONCLUSIONS: Patients adherent to ACE inhibitors/ARBs and statins only had similar mortality rates as those adherent to all 3 therapies, suggesting limited additional benefit for beta-blockers in patients who were adherent to statins and ACE inhibitors/ARBs. Nonadherence to ACE inhibitors/ARBs and/or statins was associated with higher mortality.

Determining When to Add Nonstatin Therapy: A Quantitative Approach.

BACKGROUND: Costs and uncertainty about the benefits of nonstatin therapies limit their use. OBJECTIVES: The authors sought to identify patients who might benefit from the addition of a nonstatin to background statin therapy. METHODS: We performed systematic reviews of subgroup analyses from randomized trials and observational studies with statin-treated participants to determine estimated 10-year absolute risk of atherosclerotic cardiovascular disease (ASCVD) and to define high-risk and very high-risk patients. We used the relative risk reductions for the addition of a nonstatin to lower low-density lipoprotein (LDL-C) used to determine the number needed to treat (NNT) to prevent 1 ASCVD event over 5 years for each patient group and to allow comparisons with 5-year cost analyses. RESULTS: The 10-year ASCVD risk is at least 30% (very high risk) for statin-treated participants with clinical ASCVD and comorbidities, and 20% to 29% (high risk) for those with ASCVD without comorbidities or who have heterozygous familial hypercholesterolemia. Adding ezetimibe to reduce low-density LDL-C by 20% would provide a 5-year NNT ≤50 for very high-risk patients with LDL-C ≥130 mg/dl or for high-risk patients with LDL-C ≥190 mg/dl, and an NNT ≤30 for very high-risk patients with LDL-C ≥160 mg/dl. Adding a PCSK9 monoclonal antibody to lower LDL-C by at least 50% would provide an NNT ≤50 for very high-risk and high-risk patients with LDL-C ≥70 mg/dl, and an NNT ≤30 for very high-risk and high-risk patients with an LDL-C ≥130 mg/dl. CONCLUSIONS: Adding ezetimibe or PCSK9 monoclonal antibodies to maximally tolerated statin therapy may be cost effective in very high-risk and high-risk patients, depending on baseline LDL-C levels.

Nonstatins and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors: Role in Non-Familial Hypercholesterolemia.

After maximizing statin and lifestyle adherence, some patients may benefit from additional low-density lipoprotein cholesterol (LDL-C) lowering. The potential for net benefit from added therapy can inform nonstatin decision-making. Considering patient risk and the LDL-C level on statin, the additional potential cardiovascular disease (CVD) risk reduction benefit from further lowering LDL-C depends on the magnitude of LDL-C lowering from the nonstatin. Ezetimibe is the only nonstatin shown to reduce atherosclerotic CVD events added to a statin, albeit modestly, since it modestly reduces LDL-C by about 20%. Proprotein Convertase Subtilisin-Like/Kexin Type 9 mononclonal antibodies lower LDL-Cby 45-65%, but definitive CVD outcomes and safety trials are pending. Niacin and fenofibrate do not clearly reduce CVD events in statin-treated patients, and may increase adverse events. Bile acid sequestrants have not been evaluated in CVD outcome trials in statin-treated patients, and have an excess of adverse effects. Cost also plays a role in access to nonstatin therapy. These considerations may inform shared decision-making.

Evidence-Based Policy Making: Assessment of the American Heart Association's Strategic Policy Portfolio: A Policy Statement From the American Heart Association.

BACKGROUND: American Heart Association (AHA) public policy advocacy strategies are based on its Strategic Impact Goals. The writing group appraised the evidence behind AHA's policies to determine how well they address the association's 2020 cardiovascular health (CVH) metrics and cardiovascular disease (CVD) management indicators and identified research needed to fill gaps in policy and support further policy development. METHODS AND RESULTS: The AHA policy research department first identified current AHA policies specific to each CVH metric and CVD management indicator and the evidence underlying each policy. Writing group members then reviewed each policy and the related metrics and indicators. The results of each review were summarized, and topic-specific priorities and overarching themes for future policy research were proposed. There was generally close alignment between current AHA policies and the 2020 CVH metrics and CVD management indicators; however, certain specific policies still lack a robust evidence base. For CVH metrics, the distinction between policies for adults (age ≥20 years) and children (<20 years) was often not considered, although policy approaches may differ importantly by age. Inclusion of all those <20 years of age as a single group also ignores important differences in policy needs for infants, children, adolescents, and young adults. For CVD management indicators, specific quantitative targets analogous to criteria for ideal, intermediate, and poor CVH are lacking but needed to assess progress toward the 2020 goal to reduce deaths from CVDs and stroke. New research in support of current policies needs to focus on the evaluation of their translation and implementation through expanded application of implementation science. Focused basic, clinical, and population research is required to expand and strengthen the evidence base for the development of new policies. Evaluation of the impact of targeted improvements in population health through strengthened surveillance of CVD and stroke events, determination of the cost-effectiveness of policy interventions, and measurement of the extent to which vulnerable populations are reached must be assessed for all policies. Additional attention should be paid to the social determinants of health outcomes. CONCLUSIONS: AHA's public policies are generally robust and well aligned with its 2020 CVH metrics and CVD indicators. Areas for further policy development to fill gaps, overarching research strategies, and topic-specific priority areas are proposed.

Association Between Preadmission Functional Status and Use and Effectiveness of Secondary Prevention Medications in Elderly Survivors of Acute Myocardial Infarction.

OBJECTIVES: To determine whether function-related indicators (FRIs), derived from preadmission claims data, help explain the frequent practice of forgoing secondary prevention medications observed in Medicare. DESIGN: Retrospective cohort. SETTING: National Medicare data. PARTICIPANTS: Elderly Medicare beneficiaries discharged alive from an acute myocardial infarction (AMI) hospitalization in 2007-2008 (N = 184,156). MEASUREMENTS: Study outcomes were number of guideline-recommended secondary prevention medications (statins, beta-blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) used after discharge and 12-month survival. Preadmission data (FRIs, cardiovascular conditions, comorbid conditions), type of AMI (non-ST-elevation myocardial infarction, anterior, other), and procedures and complications during the hospitalization were from claims data. RESULTS: Function-related indicators (FRIs) were common before admission; 50% of individuals had at least one (range 0-11). After discharge, 85.8% used at least one class of guideline medication, and 30.2% used all three; 19.6% died within 12 months. Each additional FRI reduced the likelihood of receiving all three medication classes by 5% (adjusted odds ratio = 0.95, 95% confidence interval (CI) = 0.94-0.96) and increased 12-month mortality by 20% (adjusted hazard ratio (aHR) = 1.20, 95% CI = 1.19-1.21). Individuals taking all three classes of medication were 30% less likely to die within 12 months than those not taking guideline medications (aHR = 0.70, 95% CI = 0.67-0.73). Similar survival benefit was observed in individuals with and without functional impairments. CONCLUSION: Greater impairment in preadmission functional status, using a measure derived from claims data, was associated with less use of secondary prevention medications after AMI. Survival benefits of taking these medications were consistent across functional impairment levels.

Correlates of Successful Aging in Racial and Ethnic Minority Women Age 80 Years and Older: Findings from the Women's Health Initiative.

BACKGROUND: Most research has focused on definitions and predictors of successful aging. However, racial/ethnic minorities are often under represented in this research. Given that the U.S. population is aging and becoming more racially diverse, we examined correlates of "successful aging," as defined by physical functioning and overall quality of life (QOL), among racial/ethnic minority women aged 80 years and older in the Women's Health Initiative. METHODS: Participants included 1,924 racial/ethnic minority women (African Americans, Asian/Pacific Islanders, Hispanic/Latinos, and American Indian/Alaskan Natives) 80 years of age and older who are enrolled in the Women's Health Initiative and have physical functioning data after turning 80 years of age. Analysis of covariance was used to examine between and within group differences in physical functioning and selfrated overall QOL for African Americans, Asian/Pacific Islanders, and Hispanic/Latinos. RESULTS: We found no significant differences in physical functioning between racial/ethnic minority groups in adjusted analyses. However, overall QOL was significantly different between racial/ethnic minority groups. Age, recreational physical activity, and overall selfrated health were independent correlates of physical functioning across racial/ethnic minority groups, whereas overall selfrated health was the only consistent correlate of overall QOL across the minority groups for the within minority group comparisons. CONCLUSIONS: Between racial/ethnic minority group differences in physical functioning are largely explained by demographic, psychosocial, behavioral, and health-related variables. We found statistically significant differences in selfrated overall QOL between racial/ethnic minority groups.

Embedding clinical interventions into observational studies.

Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed.

Design and rationale for the Patient and Provider Assessment of Lipid Management (PALM) registry.

BACKGROUND: Despite improvements in diagnosis and treatment, the prevalence of hyperlipidemia among adults in the United States remains high. Data are limited on treatment patterns and patient perceptions of cardiovascular disease risk since the release of new lipid guidelines. OBJECTIVES: The objectives of the PALM registry are to assess contemporary patterns of lipid-lowering therapy use among adults receiving care in a nationally representative cohort of community clinics, determine consistency of treatment with varying lipid guidelines, identify factors affecting use of lipid-lowering therapy including patient-reported statin intolerance, and assess patient and provider knowledge of cardiovascular risk reduction goals. STUDY DESIGN: The PALM registry will enroll 7,500 patients likely to be considered for lipid-lowering therapy from 175 cardiology, primary care, and endocrinology practices across the United States. In this cross-sectional, observational registry, a novel tablet-based platform will be used to collect patient-reported knowledge, attitudes, and beliefs regarding cardiovascular risk reduction and lipid management. Chart abstraction and core laboratory lipid levels will describe current lipid management. Provider surveys will assess perception of current lipid-lowering goals and barriers to optimal cardiovascular risk reduction. CONCLUSION: The PALM registry will allow for better understanding of current practice patterns, patient experiences, and patient and provider attitudes toward cholesterol management for cardiovascular disease risk reduction. These data can be used to better understand gaps in care and design targeted interventions to improve uptake of lipid-lowering therapies for cardiovascular risk reduction.