L. Veronica Lee

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.

Efficacy of alirocumab according to background statin type and dose: pooled analysis of 8 ODYSSEY Phase 3 clinical trials

Low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 monoclonal antibody alirocumab may be affected by background statin dose due to increased PCSK9 levels with higher statin doses. Data from 8 Phase 3 trials conducted with background statin (n = 4629) were pooled by alirocumab dose (75 or 150 mg every 2 weeks) and control (placebo/ezetimibe), and analyzed by background statin type/dose. Overall, 58.4% received high-dose statins (atorvastatin 40–80 mg, rosuvastatin 20–40 mg, simvastatin 80 mg), 28.6% moderate-dose statins (atorvastatin 20–<40 mg, rosuvastatin 10–<20 mg, simvastatin 40–<80 mg), and 12.9% low-dose statins (atorvastatin <20 mg, rosuvastatin <10 mg, simvastatin <40 mg). Mean baseline PCSK9 levels were higher with high versus moderate and low statin doses (318.5 vs 280.6 ng/mL). Baseline LDL-C levels were similar across pools, regardless of statin intensity. No associations were observed between statin type/dose and LDL-C % change from baseline or % of patients achieving LDL-C goals at Week 24 for alirocumab versus control (interaction P-values non-significant). Incidence of adverse events was similar for alirocumab versus control, except for a higher rate of injection-site reactions with alirocumab. In summary, alirocumab provided consistent LDL-C reductions and was generally well tolerated independent of background statin type/dose.

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.

Association of Patient Perceptions of Cardiovascular Risk and Beliefs on Statin Drugs With Racial Differences in Statin Use: Insights From the Patient and Provider Assessment of Lipid Management Registry

Importance African American individuals face higher atherosclerotic cardiovascular disease risk than white individuals; reasons for these differences, including potential differences in patient beliefs regarding preventive care, remain unknown. Objective To evaluate differences in statin use between white and African American patients and identify the potential causes for any observed differences. Design, Setting, and Participants Using the 2015 Patient and Provider Assessment of Lipid Management (PALM) Registry data, we compared statin use and dosing between African American and white outpatient adults who were potentially eligible for primary or secondary prevention statins. A total of 138 US community health care practices contributed to the data. Data analysis was conducted from March 2017 to May 2018. Main Outcomes and Measures Primary outcomes were use and dosing of statin therapy according to the 2013 American College of Cardiology/American Heart Association guideline by African American or white race. Secondary outcomes included lipid levels and patient-reported beliefs. Poisson regression was used to evaluate the association between race and statin undertreatment, a category combining people who were not taking a statin or those taking a dose intensity lower than recommended. Results A total of 5689 patients (806 [14.2%] African American) in the PALM registry were eligible for statin therapy. African American individuals were less likely than white individuals to be treated with a statin (570/807 [70.6%] vs 3654/4883 [74.8%]; P = .02). Among those treated, African American patients were less likely than white patients to receive a statin at guideline-recommended intensity (269 [33.3%] vs 2145 [43.9%], respectively; P < .001; relative risk, 1.07 [95% CI, 1.00-1.15]; P = .05, after adjustment for demographic and clinical factors). The median (interquartile range) low-density lipoprotein cholesterol levels of patients receiving treatment were higher among African American than white individuals (97.0 [76.0-121.0] mg/dL vs 85.0 [68.0-105.0] mg/dL; P < .001). African American individuals were less likely than white individuals to believe statins were safe (292 [36.2%] vs 2800 [57.3%]; P < .001) or effective (564 [70.0%] vs 3635 [74.4%]; P = .008) and were less likely to trust their clinician (663 [82.3%] vs 4579 [93.8%]; P < .001). Group differences in statin undertreatment were not significant after adjusting for demographic, clinical, and clinician factors, socioeconomic status, and patient beliefs (final adjusted relative risk, 1.03 [95% CI 0.96–1.11]; P = .35). Conclusions and Relevance African American individuals were less likely to receive guideline-recommended statin therapy. Demographic, clinical, socioeconomic, belief-related, and clinician differences contributed to observed differences and represent potential targets for intervention.

Statin Use and Adverse Effects Among Adults >75 Years of Age: Insights From the Patient and Provider Assessment of Lipid Management (PALM) Registry

Background Current statin use and symptoms among older adults in routine community practice have not been well characterized since the release of the 2013 American College of Cardiology/American Heart Association guideline. Methods and Results We compared statin use and dosing between adults >75 and ≤75 years old who were eligible for primary or secondary prevention statin use without considering guideline‐recommended age criteria. The patients were treated at 138 US practices in the Patient and Provider Assessment of Lipid Management (PALM) registry in 2015. Patient surveys also evaluated reported symptoms while taking statins. Multivariable logistic regression models examined the association between older age and statin use and dosing. Among 6717 people enrolled, 1704 (25%) were >75 years old. For primary prevention, use of any statin or high‐dose statin did not vary by age group: any statin, 62.6% in those >75 years old versus 63.1% in those ≤75 years old (P=0.83); high‐dose statin, 10.2% versus 12.3% in the same groups (P=0.14). For secondary prevention, older patients were slightly less likely to receive any statin (80.1% versus 84.2% [P=0.003]; adjusted odds ratio, 0.81; 95% confidence interval, 0.66–1.01 [P=0.06]), but were much less likely to receive a high‐intensity statin (23.5% versus 36.2% [P<0.0001]; adjusted odds ratio, 0.54; 95% confidence interval, 0.45–0.65 [P=0.0001]). Among current statin users, older patients were slightly less likely to report any symptoms (41.3% versus 46.6%; P=0.003) or myalgias (27.3% versus 33.3%; P<0.001). Conclusions Overall use of statins was similar for primary prevention in those aged >75 years versus younger patients, yet older patients were less likely to receive high‐intensity statins for secondary prevention. Statins appear to be similarly tolerated in older and younger adults.

Prevalence and Management of Symptoms Associated With Statin Therapy in Community Practice: Insights From the PALM (Patient and Provider Assessment of Lipid Management) Registry

When compared against placebo in randomized trials, statins are extremely well tolerated, causing muscle-related side effects in 1% or fewer of treated patients.1 Yet in routine practice, patients often report having symptoms which are misattributed to their statin.2–4 Using data from the PALM Registry, we examined patient-reported rates of statin intolerance, characteristics of patients with perceived side effects, and response to perceived statin intolerance in contemporary practice. The data, analytic methods, and study materials will not be made available to other researchers for purposes of reproducing the results. The PALM Registry enrolled 7938 patients from 140 primary care, cardiology, and endocrinology practices in the United States (May 27, 2015 to November 12, 2015) and has been described in detail.5 Trained study coordinators identified eligible patients (patients on a statin, at risk for cardiovascular disease [CVD], or with prevalent CVD, in the Data Supplement) at the time of their visit, who were then sequentially enrolled. Of 9788 eligible patients, n=7937 (81%) consented and enrolled in the study. Patients were then surveyed on statin use, perceived statin-related symptoms and response to symptoms, beliefs about statins and CVD, and sociodemographic characteristics (response rate 95.3%, in the Data Supplement). Clinical characteristics and medications were abstracted from the medical record by study coordinators. All patients had core laboratory lipid levels (LabCorp, Burlington, NC). Categorical variables were compared with Mantel–Haenszel χ2 tests and continuous variables using Wilcoxon rank-sum tests. Multivariable logistic regression modeling was used to evaluate factors associated with symptoms using generalized estimating equations to account for clustering within site, with backward model selection at P <0.05 for variable retention. Candidate variables were chosen based on either associations with statin use (eg, demographics, atherosclerotic cardiovascular disease history, education, and insurance) or prior associations with statin intolerance (eg, thyroid …

Efficacy and safety of alirocumab in patients with or without prior coronary revascularization: Pooled analysis of eight ODYSSEY phase 3 trials

BACKGROUND AND AIMS Patients with atherosclerotic cardiovascular disease (ASCVD) and prior revascularization are at high risk of further cardiovascular events and may require additional lipid-lowering therapies beyond maximally tolerated statin therapy. We assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in patients with ASCVD, with or without prior coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]). METHODS Data from eight controlled (placebo/ezetimibe) phase 3 ODYSSEY trials were pooled and stratified by trial design: alirocumab 150 mg or 75 mg with possible dose increase to 150 mg (75/150 mg) every 2 weeks (Q2W) versus placebo, and alirocumab 75/150 mg Q2W versus ezetimibe. Most patients received background maximally tolerated statin therapy. RESULTS Among 4629 randomized patients with hypercholesterolemia, 3382 had ASCVD including 2191 with prior revascularization. Although baseline characteristics were comparable between alirocumab and control groups, revascularized patients were more likely to be male, have had prior myocardial infarction/stroke, have higher lipoprotein (a) and PCSK9 levels, and were more often treated with high-intensity statin therapy. Alirocumab significantly reduced low-density lipoprotein cholesterol (LDL-C; primary endpoint; p < 0.0001), lipoprotein (a), non-high-density lipoprotein cholesterol, and apolipoprotein B levels from baseline to week 24 (vs. control), regardless of stratified treatment group or revascularization status. On-treatment LDL-C levels with alirocumab ranged from 45.6 to 64.8 mg/dL. Alirocumab had a similar safety profile regardless of revascularization status, and higher rates of injection-site reactions versus controls. CONCLUSIONS Alirocumab is generally well-tolerated and effective with a similar safety profile in high-risk patients with or without prior revascularization (PCI/CABG).

PREVALENCE AND MANAGEMENT OF PATIENT-REPORTED SYMPTOMS ON STATIN THERAPY: INSIGHTS FROM THE PATIENT AND PROVIDER ASSESSMENT OF LIPID MANAGEMENT (PALM) REGISTRY

The definition of “statin intolerance” varies among patients and providers, with myalgia prevalence from 1-5% in clinical trials up to 29% in observational studies. The PALM Registry collected patient perspectives on statin-related symptoms and strategies used to continue treatment. We surveyed

PATIENTS’ PERCEIVED VERSUS PREDICTED CARDIOVASCULAR DISEASE RISK: CHALLENGES FOR SHARED DECISION-MAKING IN CHOLESTEROL MANAGEMENT

Current cholesterol management strategies for prevention of cardiovascular disease (CVD) emphasize risk assessment for patient engagement in shared decision-making. We asked 1011 patients ages 40+ free of CVD from 59 primary care, cardiology, and endocrine clinics in the Patient and Provider