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Head-to-head studies comparing COVID-19 mRNA vaccine effectiveness in immunocompromised individuals, who are vulnerable to severe disease are lacking, as large sample sizes are required to make meaningful inferences.This observational comparative effectiveness study was conducted in closed administrative claims data from the US HealthVerity database (December 11, 2020-January 10, 2022, before omicron). A 2-dose mRNA-1273 versus BNT162b2 regimen was assessed for preventing medically-attended breakthrough COVID-19 diagnosis and hospitalizations among immunocompromised adults. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) using weighted Cox proportional hazards models were calculated.Overall, 57,898 and 66,981 individuals received a 2-dose regimen of mRNA-1273 or BNT161b2, respectively. Among the weighted population, mean age was 51 years, 53 % were female, and baseline immunodeficiencies included prior blood transplant (8%-9%), prior organ transplant (7%), active cancer (12%-13%), primary immunodeficiency (5-6%), HIV (20%-21%), and immunosuppressive therapy use (60%-61%). Rates per 1,000 person-years (PYs; 95% confidence intervals [CI]s) of breakthrough medically-attended COVID-19 were 25.82 (23.83-27.97) with mRNA-1273 and 30.98 (28.93, 33.18) with BNT162b2 (HR, 0.83; 95% CI, 0.75-0.93). When requiring evidence of an antigen or polymerase chain reaction test before COVID-19 diagnosis, the HR for medically-attended COVID-19 was 0.78 (0.67-0.92). Breakthrough COVID-19 hospitalization rates per 1,000 PYs (95% CI) were 3.66 (2.96-4.51) for mRNA-1273 and 4.68 (3.91-5.59) for BNT162b2 (HR, 0.78; 0.59-1.03). Utilizing open and closed claims for outcome capture only, or both cohort entry/outcome capture, produced HRs (95% CIs) for COVID-19 hospitalization of 0.72 (0.57-0.92) and 0.66 (0.58-0.76), respectively.Among immunocompromised adults, a 2-dose mRNA-1273 regimen was more effective in preventing medically-attended COVID-19 in any setting (inpatient and outpatient) than 2-dose BNT162b2. Results were similar for COVID-19 hospitalization, although statistical power was limited when using closed claims only.NCT05366322.

Background Adults with atherosclerotic cardiovascular disease (ASCVD) at very high-risk for recurrent events who have low-density lipoprotein cholesterol ≥ 70 mg/dL despite maximally-tolerated statin therapy are recommended to initiate ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Objective Compare the initiation of ezetimibe and a PCSK9 inhibitor after a myocardial infarction (MI) among very high-risk ASCVD patients by race/ethnicity and sex. Methods We analyzed data from 374,786 adults ≥ 66 years of age with Medicare fee-for-service coverage who had an MI between July 1, 2015 and December 31, 2018, were not taking ezetimibe or a PCSK9 inhibitor, and had very high-risk ASCVD defined by the 2018 American Heart Association/American College of Cardiology multi-society cholesterol guideline. Pharmacy claims through December 31, 2018 were used to determine ezetimibe and PCSK9 inhibitor initiation. Results Overall, 6980 (1.9%) beneficiaries initiated ezetimibe, and 1433 (0.4%) initiated a PCSK9 inhibitor. Adjusted hazard ratios (aHR) for ezetimibe initiation among non-Hispanic Black, Hispanic, and Asian versus non-Hispanic White beneficiaries were 0.77 (95% confidence interval [95%CI]: 0.70–0.86), 0.92 (95%CI: 0.76–1.11) and 0.73 (95%CI: 0.59–0.89), respectively. Compared to non-Hispanic White beneficiaries, the aHRs for PCSK9 inhibitor initiation were 0.63 (95%CI: 0.48–0.81) among non-Hispanic Black, 0.70 (95%CI: 0.43–1.13) among Hispanic, and 0.93 (95%CI: 0.62–1.39) among Asian beneficiaries. The aHRs for ezetimibe and PCSK9 inhibitor initiation comparing women to men were 1.11 (95%CI: 1.06–1.17) and 1.13 (95%CI: 1.01–1.25), respectively. Conclusion There are race/ethnic and sex disparities in the initiation of ezetimibe and a PCSK9 inhibitor following MI among very high-risk ASCVD patients.

Rationale & Objective: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline uses risk stratification to guide the decision to initiate nonstatin lipid-lowering medication among adults with atherosclerotic cardiovascular disease (CVD). We determined atherosclerotic CVD (ASCVD) event rates among adults with chronic kidney disease (CKD) taking statin therapy within 2018 AHA/ACC cholesterol guideline risk categories. Study Design: Observational cohort study. Setting & Participants: Adults with CKD not on dialysis in the Chronic Renal Insufficiency Cohort (CRIC) study who were taking a moderate/high-intensity statin 1 year after enrollment (baseline for the current analysis, n = 1,753). Exposure: 2018 AHA/ACC cholesterol guideline risk categories: without a history of ASCVD, a history of 1 major ASCVD event and multiple high-risk conditions, and a history of ≥2 major ASCVD events. Outcome: Adjudicated ASCVD events after the year 1 study visit. Analytical Approach: We calculated age-sex standardized rates for ASCVD events and age-sex adjusted hazard ratios for ASCVD events accounting for the competing risk of death. Results: There were 394 ASCVD events over a median follow-up period of 8 years. The ASCVD event rates (with 95% CI) per 1,000 person-years among participants without a history of ASCVD, with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 21.7 (18.4-25.1), 45.0 (37.8-52.3), and 73.3 (53.3-93.4), respectively. Compared with participants without a history of ASCVD, the HR (95% CI) rates for ASCVD events among those with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 1.89 (1.52-2.36) and 2.50 (1.85-3.39), respectively. Limitations: Data on whether participants were taking a maximally tolerated statin dosage were unavailable. Conclusions: The 2018 AHA/ACC cholesterol guideline identifies adults with CKD who have very high ASCVD risk despite taking a moderate/high-intensity statin.

Author(s): Fonarow, Gregg C; Kosiborod, Mikhail N; Rane, Pallavi B; Nunna, Sasikiran; Villa, Guillermo; Habib, Mohdhar; Arellano, Jorge; Mues, Katherine E; Sun, Kainan; Wade, Rolin L | Abstract: BackgroundThe risk for subsequent major cardiovascular (CV) events among patients with very high-risk (VHR) atherosclerotic CV disease (ASCVD) remains to be fully elucidated.HypothesisWe assessed the characteristics and major CV event rates of patients with VHR versus non-VHR ASCVD in a real-world setting in the United States (US), hypothesizing that patients with VHR ASCVD would have higher CV event rates.MethodsThis was a retrospective cohort study conducted from January 01, 2011, to June 30, 2018, in the US using the Prognos LDL-C database linked to the IQVIA PharMetrics Plus® database supplemented with the IQVIA prescription claims (Dx/LRx) databases. Patients were ≥18 years old and had ≥2 non-ancillary medical claims in the linked databases at least 30 days apart. The study was conducted in 2 stages: (1) identification of patients with ASCVD who met the definition of VHR ASCVD and a matched cohort of non-VHR ASCVD patients using the incidence density sampling (IDS) approach; (2) estimation of the occurrence of major CV events.ResultsAmong patients with ≥1 major ASCVD event (N=147,679), most qualified as VHR ASCVD (79.5%). There were 115,460 patients each in IDS-matched VHR and non-VHR ASCVD cohorts. The composite myocardial infarction/ischemic stroke event rates in the VHR and non-VHR ASCVD cohorts were 8.04 (95% confidence interval [95% CI]: 7.87-8.22) and 0.82 (95% CI: 0.77-0.88) events per 100 patient-years, respectively, during the 1-year post-index period.ConclusionsMost patients with ≥1 previous major ASCVD event treated in real-world US clinical practice qualified as VHR ASCVD. Patients with VHR ASCVD had much higher rates of major CV events versus non-VHR ASCVD patients.

Chronic kidney disease (CKD) is a known risk factor of atherosclerotic cardiovascular disease (ASCVD). Per the 2018 American Heart Association/American College of Cardiology cholesterol guidelines, high-risk ASCVD patients with CKD and low-density lipoprotein cholesterol (LDL-C) levels We examined the changes in use of lipid lowering therapies (LLT) over two years in 3304 patients with ASCVD and CKD in the Getting to an imprOved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) observational cohort study.Of those with eGFR60 ml/min/1.73 mDespite the recommendations of multiscociety guidelines, statin use, while high, is not ubiquitous and rates of high-intensity statin and ezetimibe use remain low in patients with CKD. There remains a significant opportunity to optimize LLT and achieve atheroprotective cholesterol levels in the CKD population.

PURPOSE: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline defines very high atherosclerotic cardiovascular disease (ASCVD) risk as a history of ≥2 major ASCVD events or 1 major ASCVD event and multiple high-risk conditions. We tested if a simplified approach, having a history of a major ASCVD event, would identify a high proportion of patients that meet the 2018 AHA/ACC cholesterol guideline criteria for very high risk. METHODS: We analyzed data from US adults with health insurance in the MarketScan database who had experienced an acute coronary syndrome in the past year (recent ACS, n=3,626), a myocardial infarction (MI) other than a recent ACS (n=7,572), an ischemic stroke (n=3,551) or symptomatic peripheral artery disease (PAD, n=5,919). Patients were followed from January 1, 2016 through December 31, 2017 for recurrent ASCVD events. RESULTS: Among 16,344 patients with a history of a major ASCVD event, 94.0% met the 2018 AHA/ACC cholesterol guideline definition for very high risk including 92.9%, 96.5%, 93.1%, and 96.2% with a recent ACS, history of MI, history of stroke and symptomatic PAD, respectively. The incidence of ASCVD events per 1,000 person-years was 50.4 (95% CI: 47.6-53.3) among all patients with a history of a major ASCVD event versus 53.1 (95% CI: 50.1-56.1) among patients who met the 2018 AHA/ACC cholesterol guideline definition of very high risk. CONCLUSION: The vast majority of patients with a recent ACS, history of MI, ischemic stroke or symptomatic PAD meet the 2018 AHA/ACC cholesterol guideline definition of very high risk.

Background Guidelines recommend adults who discontinue statin therapy because of statin-associated symptoms be reinitiated. Low-density lipoprotein cholesterol (LDL-C) levels achieved after statin reinitiation are unknown. Objective The objective of this study was to determine LDL-C levels after statin reinitiation. Methods We analyzed data from 5498 participants in the REasons for Geographic And Racial Differences in Stroke study who reported ever taking a statin. We categorized participants according to their pattern of statin use including those taking a statin who did not experience statin-associated symptoms and continued treatment, and those who discontinued statins because of statin-associated symptoms and were not reinitiated, reinitiated and remained on treatment, and discontinued treatment after being reinitiated. Mortality and vascular event reduction with statin reinitiation was estimated using data from the Cholesterol-Lowering Treatment Trialists Collaboration. Results After multivariable adjustment, LDL-C was 14.1 (95% CI: 9.9–18.3) mg/dL higher among participants reinitiated and taking a statin compared with those without statin-associated symptoms who continued statin therapy. Mean LDL-C was 18.1 mg/dL (95% CI: 13.0–23.1) and 27.5 mg/dL (95% CI: 20.7–34.4) lower among participants reinitiated and taking a statin compared with those who discontinued statin therapy and were not reinitiated and those who discontinued statins after being reinitiated, respectively. An LDL-C reduction of 18.1 mg/dL with statin reinitiation was projected to reduce all-cause and coronary heart disease mortality by 5.6% and 8.9%, respectively, and myocardial infarction or coronary heart disease death and major vascular events by 10.7% and 9.8%, respectively, over 5 years. Conclusion Reinitiating individuals who discontinue statin therapy may reduce LDL-C and cardiovascular risk.

IntroductionHead-to-head studies comparing COVID-19 mRNA vaccine effectiveness in immunocompromised individuals, who are vulnerable to severe disease are lacking, as large sample sizes are required to make meaningful inferences.MethodsThis observational comparative effectiveness study was conducted in closed administrative claims data from the US HealthVerity database (December 11, 2020-January 10, 2022, before omicron). A 2-dose mRNA-1273 versus BNT162b2 regimen was assessed for preventing medically-attended breakthrough COVID-19 diagnosis and hospitalizations among immunocompromised adults. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) using weighted Cox proportional hazards models were calculated.ResultsOverall, 57,898 and 66,981 individuals received a 2-dose regimen of mRNA-1273 or BNT161b2, respectively. Among the weighted population, mean age was 51 years, 53% were female, and baseline immunodeficiencies included prior blood transplant (8%-9%), prior organ transplant (7%), active cancer (12%-13%), primary immunodeficiency (25%-26%), HIV (20%-21%), and immunosuppressive therapy use (60%-61%). Rates per 1,000 person-years (PYs; 95% confidence intervals [CI]s) of breakthrough medically-attended COVID-19 were 25.82 (23.83-27.97) with mRNA-1273 and 30.98 (28.93, 33.18) with BNT162b2 (HR, 0.83; 95% CI, 0.75-0.93). When requiring evidence of an antigen or polymerase chain reaction test before COVID-19 diagnosis, the HR for medically-attended COVID-19 was 0.78 (0.67-0.92). Breakthrough COVID-19 hospitalization rates per 1,000 PYs (95% CI) were 3.66 (2.96-4.51) for mRNA-1273 and 4.68 (3.91-5.59) for BNT162b2 (HR, 0.78; 0.59-1.03). Utilizing open and closed claims for outcome capture only, or both cohort entry/outcome capture, produced HRs (95% CIs) for COVID-19 hospitalization of 0.72 (0.57-0.92) and 0.66 (0.58-0.76), respectively.ConclusionsAmong immunocompromised adults, a 2-dose mRNA-1273 regimen was more effective in preventing medically-attended COVID-19 in any setting (inpatient and outpatient) than 2-dose BNT162b2. Results were similar for COVID-19 hospitalization, although statistical power was limited when using closed claims only.Study RegistrationNCT05366322

Guidelines for managing patients with atherosclerotic cardiovascular disease (ASCVD) recommend statin therapy initially. Target levels/goals for low-density lipoprotein-cholesterol (LDL-C) were initially included, subsequently de-emphasized in 2013, and then re-introduced as thresholds, leading to confusion in clinical practice. We designed a multicenter, observational registry of patients with ASCVD, to describe and track LDL-C treatment patterns in the United States over time.Patients with ASCVD receiving any pharmacologic lipid-lowering therapy were eligible for enrollment in one of three cohorts: 1) currently receiving a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), or not receiving PCSK9i with 2) LDL-C 70-99 mg/dL, or 3) LDL-C ≥100 mg/dL. Patients undergo a 1-year retrospective chart review, followed by chart reviews and phone interviews every 6 months for 2 years.A total of 5006 patients were enrolled at 119 centers. Mean age was 68 years, 40% of patients were female, 86% were white, 80% had coronary artery disease, and 33% had type 2 diabetes mellitus. Among those not on a PCSK9i, high-intensity statins and ezetimibe were utilized in only 44% and 9%, respectively. Among women vs men, only 36.6% vs 48.2% received high-intensity statins (P .001). Among patients on a PCSK9i, only one-third were receiving a statin, suggesting statin intolerance is a driver of PCSK9i use at present.Our data on current practice in the US continue to illustrate that high-intensity statins and ezetimibe are underutilized in at-risk patients outside of clinical trials, particularly women. This study will track temporal changes in treatment patterns and identify opportunities for improvement in lipid management in patients with ASCVD.

Background Because of an increasing number and complexity of treatment options for lipid‐lowering therapy in patients with atherosclerotic cardiovascular disease, guidelines recommend greater active involvement of patients in shared decision‐making. However, patients' understanding and perceptions of the benefits, risks, and treatment objectives of lipid‐lowering therapy are unknown. Methods and Results Structured questionnaires were conducted in 5006 US outpatients with atherosclerotic cardiovascular disease and suboptimal low‐density lipoprotein cholesterol (LDL‐C) control (LDL‐C ≥70 mg/dL) or on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor and in 113 physician providers as a part of the GOULD (Getting to an Improved Understanding of Low‐Density Lipoprotein Cholesterol and Dyslipidemia Management) Registry. Mean age of the patients was 68±10 years, 60% were men, and 86% were White race. Across all patients, 63% believed heart disease was the leading cause of death in men and 46% the leading cause of death in women. Only 28% of patients thought the primary reason they were taking lipid‐lowering medication was to lower the risk of heart attack or stroke, 68% did not know their approximate LDL‐C level, and 69% did not know their LDL‐C goal. Patients on PCSK9 inhibitors (versus LDL‐C cohort), younger patients (versus age ≥65 years), and men (versus women) were somewhat more knowledgeable about their disease and its management. Most physicians (66%) felt that a lack of understanding of the importance and efficacy of statins was the primary factor contributing to nonadherence, as opposed to costs (9%) or side effects (1%). More education was the most commonly used strategy to address patient‐reported side effects. Conclusions A large proportion of patients with atherosclerotic cardiovascular disease remain unaware of their underlying atherosclerotic cardiovascular disease risk, reasons for taking lipid‐lowering medications, current LDL‐C levels, or treatment goals. These data highlight a large education gap which, if addressed, may improve shared decision‐making and treatment adherence. Registration URL: https://www.clinicaltrials.org ; Unique identifier: NCT02993120.

Background Low‐density lipoprotein cholesterol (LDL‐C) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited real‐world data on LDL‐C lowering with evolocumab in United States clinical practice. Hypothesis We assessed LDL‐C lowering during 1 year of evolocumab therapy. Methods This retrospective cohort study used linked laboratory (Prognos) and medical claims (IQVIA Dx/LRx and PharMetrics Plus®) data. Patients with a first fill for evolocumab between 7/1/2015 and 10/31/2019 (index event) and LDL‐C ≥ 70 mg/dL were included (overall cohort; N = 5897). Additionally, a patient subgroup with a recent myocardial infarction (MI) within 12 months (median 130 days) before the first evolocumab fill was identified (N = 152). Reduction from baseline LDL‐C was calculated based on the lowest LDL‐C value recorded during a 12‐month follow‐up period. Results The mean (SD) age was 65 (10) years; 61.9% of patients had ASCVD diagnoses and 70.7% of patients were in receipt of lipid‐lowering therapy. Following evolocumab treatment, changes in LDL‐C from baseline were −60% in the overall cohort (median [interquartile range (IQR)] 146 [115–180] mg/dL to 58 [36–84] mg/dL) and −65% in the recent MI subgroup (median [IQR] 137 [109–165] mg/dL to 48 [30–78] mg/dL). In the overall cohort and recent MI subgroup, 62.1% and 69.7% of patients achieved LDL‐C

Low-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in peripheral artery disease (PAD). Lipid-lowering therapies (LLT) that reduce LDL-C decrease this risk.The authors examined LLT use and actual achieved LDL-C in PAD.PAD patients in MarketScan from 2014 to 2018 were identified. Outcomes included LLT use, defined as high-intensity (HI) (high-intensity statin, statin plus ezetimibe, or PCSK9 inhibitor), low-intensity (any other lipid regimen), or no therapy, and follow-up LDL-C. Factors associated with LDL-C70 mg/dl were identified with multivariable logistic regression.Among 250,103 PAD patients, 20.5% and 39.5% were treated at baseline with HI and low-intensity LLT, respectively; 40.0% were on no LLT. Over a 15-month median follow-up period, HI LLT use increased by 1.5%. Among 18,747 patients with LDL-C data, at baseline, 25.1% were on HI LLT, median LDL-C was 91 mg/dl, and 24.5% had LDL-C 70 mg/dl. Within the HI LLT subgroup, median LDL-C was 81 mg/dl, and 64% had LDL-C ≥70 mg/dl. At follow-up, HI LLT use increased by 3.7%, median LDL-C decreased by 4.0 mg/dl, and an additional 4.1% of patients had LDL-C 70 mg/dl. HI LLT use was greater after follow-up MACE (55.0%) or MALE (41.0%) versus no ischemic event (26.1%). After MACE or MALE, LDL-C was 70 mg/dl in 41.5% and 36.1% of patients, respectively, versus 27.1% in those without an event. Factors associated with follow-up LDL-C 70 mg/dl included smoking, hypertension, diabetes, prior lower extremity revascularization, and prior myocardial infarction but not prior acute or critical limb ischemia.In PAD, LLT use is suboptimal, LDL-C remains elevated, and LLT intensity is a poor surrogate for achieved LDL-C. Less aggressive lipid management was observed in PAD versus cardiovascular disease, highlighting missed opportunities for implementation of proven therapies in PAD.

Introduction: Low-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Strategies that lower LDL-C levels reduce this risk. Hypothesis: We hypothesized that real-world PAD patients are overall undertreated with lipid lowering therapies (LLT) but that LLT use and achieved LDL-C are improved in high risk patients with ischemic events. Methods: Patients with PAD in the MarketScan database linked to PROGNOS lab data from January 1, 2014 through December 31, 2018 were examined. Outcomes included use of LLT, defined as high intensity (HI) (high intensity statin, any statin plus ezetimibe, or any use of a PCSK9 inhibitor), low intensity (LI) (any other lipid regimen), or no therapy, and follow up LDL-C level. Goal LDL-C was defined as Results: Among 18,747 PAD patients, 25% were on HI LLT, 43% were on LI LLT, and 32% were on no therapy at baseline (Figure A). The median LDL-C was 91 mg/dl (IQR 70, 118), and 25% of patients were at goal (Figure B). After a median follow up of 18 months, use of HI LLT increased by 4%, the median LDL-C decreased by 5 mg/dl, and an additional 3% of patients were at goal LDL-C. Greater use of HI LLT was observed among patients with a MACE (55%) or MALE (41%) event during follow up compared with patients without an ischemic event (26%) during follow up (Figure C). Follow up LDL-C levels remained above goal for most patients (post-MACE: median LDL-C 77 mg/dl, 42% patients at goal; post-MALE: median LDL-C 80 mg/dl, 36% patients at goal). Conclusions: In PAD patients, use of LLT is suboptimal, and LDL-C levels remain elevated. After an ischemic event, LLT use is intensified, with greater use of HI LLT observed after MACE than MALE. Despite this, LLT remains underutilized, with >50% of patients not at goal LDL-C. Strategies to better implement proven therapies to reduce risk in this high risk population are needed.

Background: Among people with ASCVD, those with T2D have excess CVD risk and derive greater absolute benefit from CVD risk reduction therapies. We describe the use of evidence-based therapies for secondary prevention in participants (pts) with T2D. Methods: We report a registry to longitudinally describe LDL-C treatment patterns among U.S. pts with ASCVD and LDL-C ≥70mg/dL taking lipid-lowering therapy. Pts (n=5006) were enrolled in 1 of 3 cohorts: taking PCSK9i (11%); LDL-C 70-99mg/dL (53%); and LDL-C ≥100mg/dL (36%). Results: Overall, 1655 (33%) had diabetes (96% with T2D): 146 in the PCSK9i cohort, 874 in the LDL-C 70-99mg/dL cohort, and 635 in the LDL-C ≥100mg/dL cohort. Mean age among pts with diabetes was 68 y, 60% were male, 81% had CAD (including 33% with prior MI), 17% with PAD, and 17% had HF. Mean LDL-C was 100mg/dL. Although overall statin use was at 87%, high-intensity statins were used in only 45% and ezetimibe in only 9.5% of pts. Aspirin and ACE-I/ARB were each used in 72% and beta blockers in 71% of pts. The most commonly used glucose-lowering medications among patients with T2D were metformin (56%), insulin (34%), and sulfonylurea (22%). Only 10% and 8% of pts with T2D were treated with SGLT2i or GLP-1RA, respectively. The proportion of pts with T2D that were receiving all guideline-recommended therapies for optimal risk reduction (high-intensity statins, aspirin, ACE-I/ARB, and either SGLT2i or GLP-1RA) was just 3%. Conclusion: In GOULD, among pts with T2D, ASCVD, and LDL-C ≥70mg/dL, most are not receiving high intensity statin therapy at baseline and few receive ezetimibe. Furthermore, less than 20% are treated with glucose-lowering therapies that have a proven CVD benefit, and a strikingly low proportion receive all guideline-recommended risk reduction strategies. These results highlight an opportunity to improve care and outcomes. Disclosure M.N. Kosiborod: Consultant; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eisai Co., Ltd., GlaxoSmithKline plc., Glytec, LLC, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis AG, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. J. De Lemos: Other Relationship; Self; Amgen Inc., Novo Nordisk A/S, Regeneron Pharmaceuticals. R.S. Rosenson: Consultant; Self; CVS/Caremark, Regeneron Pharmaceuticals. Research Support; Self; Akcea Therapeutics, Amgen Inc., Medicines Company, Regeneron Pharmaceuticals. Other Relationship; Self; Amgen Inc., Kowa Pharmaceutical Europe Co. Ltd. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Esperion, Gilead Sciences, Inc., Matinas BioPharma, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., Esperion, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Other Relationship; Self; Roche Diagnostic USA. K. Philip: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. Y. Liu: None. K.E. Mues: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. S. Alam: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. M. Elliott: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. D.L. Bhatt: Research Support; Self; Abbott, Amarin Corporation, Amgen Inc., AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Chiesi USA, Inc., Eisai Inc., Eli Lilly and Company, Ethicon, Inc., FlowCo, Forest Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Inc., Ischemix, Medicines Company, Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma, Regeneron Pharmaceuticals, Roche Pharma, Sanofi, Synaptic, Takeda Pharmaceutical Company Limited. C.P. Cannon: Consultant; Self; Alnylam, Amarin Corporation, Amgen Inc., Corvia Medical, Inc., Eisai Inc., Kowa Pharmaceutical Europe Co. Ltd., Pfizer Inc., Regeneron Pharmaceuticals, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Funding Amgen Inc.

This cohort study describes the use of drug therapies to prevent the progression of atherosclerotic cardiovascular disease in US patients with prior myocardial infarction and elevated low-density lipoprotein cholesterol levels.

Background Peripheral artery disease (PAD) is associated with increased risk for atherosclerotic cardiovascular disease (ASCVD) events. Objectives The goal of this study was to compare the risk for ASCVD events and the use of statins among patients with PAD versus those with coronary heart disease (CHD) or cerebrovascular disease. Methods The authors conducted a retrospective cohort study of adults age ≥19 years with commercial or Medicare health insurance who had a history of PAD, CHD, or cerebrovascular disease on December 31, 2014. Patients were followed for ASCVD events comprising CHD, cerebrovascular disease, and PAD events until December 31, 2017. Results Among 943,232 patients included in the analysis, the age-standardized ASCVD event rate per 1,000 person-years for those with a history of 1, 2, and 3 conditions including PAD, CHD, and cerebrovascular disease was 40.8 (95% confidence interval [CI]: 40.3 to 41.3), 68.9 (95% CI: 67.9 to 70.0), and 119.5 (95% CI: 117.0 to 122.0), respectively. The ASCVD event rate among patients with PAD only, CHD only, and cerebrovascular disease only was 34.7 (95% CI: 33.2 to 36.2), 42.2 (95% CI: 41.5 to 42.8), and 38.9 (95% CI: 37.6 to 40.1), respectively. Among patients with PAD and CHD, with PAD and cerebrovascular disease, and with CHD and cerebrovascular disease, the ASCVD event rate was 72.8 (95% CI: 71.0 to 74.7), 63.9 (95% CI: 60.6 to 67.4), and 67.9 (95% CI: 66.4 to 69.3), respectively. Statin use was lower in patients with PAD only (33.9%) versus those with cerebrovascular disease only (43.0%) or CHD only (51.7%). Conclusions Despite having high risk for ASCVD events, patients with PAD were less likely to be taking a statin versus those with CHD or cerebrovascular disease. ASCVD risk-reduction interventions including statin therapy in patients with PAD are warranted.

Background Proprotein convertase subtilisin/kexin type 9 inhibitors ( PCSK 9i) are used to reduce low‐density lipoprotein ( LDL ) cholesterol. PCSK 9i use after initiation, as well as persistence with or alterations to other LDL ‐lowering therapy after PCSK 9i initiation, is not well understood. Methods and Results We conducted a retrospective study of alirocumab or evolocumab ( PCSK 9i) new users from July 2015 to December 2017 in the MarketScan Early View database of US commercial insurance beneficiaries. We determined the prevalence of PCSK 9i interruption (≥30‐day gap in supply) and LDL ‐lowering therapy use in the year after PCSK 9i initiation. The average age of 6151 patients initiating PCSK 9i therapy was 63 years, 44.4% were women, and 76.8% had atherosclerotic cardiovascular disease. Overall, 52.2% (95% CI , 50.8%–53.7%) of patients had an interruption in PCSK 9i therapy in the first year after treatment initiation and 62.5% remained on PCSK 9i therapy at 1‐year postinitiation. Also, 27.7% of patients were taking a statin at the time of PCSK 9i initiation, with only 22.4% on statin therapy at 1 year after PCSK 9i initiation. Ezetimibe use decreased from 20.9% at the time of PCSK 9i initiation to 12.0% a year later. By 1 year after PCSK 9i initiation, 44.0% of patients had experienced an interruption in all LDL ‐lowering therapies, and 26.6% were no longer on any LDL ‐lowering therapies. Conclusions After PCSK 9i initiation, statins were often discontinued, whereas more than half of patients experienced an interruption in PCSK 9i therapy. These results suggest that many new PCSK 9i users may remain at high risk for cardiovascular events because of interruptions in LDL ‐lowering therapy.

Evidence suggests that statin therapy in patients with peripheral artery disease (PAD) is beneficial yet use remains suboptimal. We examined trends in statin use, intensity, and discontinuation among adults aged ⩾ 40 years with incident severe PAD and a subset with critical limb ischemia (CLI) between 2002 and 2015 within an integrated healthcare delivery system. Discontinuation of statin therapy was defined as the first 90-day gap in treatment within 1 year following PAD diagnosis. We identified 11,059 patients with incident severe PAD: 31.1% ( n = 3442) with CLI and 68.9% ( n = 7617) without CLI. Mean (SD) age was 68.6 (11.3) years, 60.5% were male, 54.2% white, 23.2% Hispanic, and 16.2% black. Statin use in the year before diagnosis increased from 50.4% in 2002 to 66.0% in 2015 (CLI: 43.7% to 68.0%; without CLI: 53.1% to 64.2%, respectively). The proportion of patients on high-intensity statins increased from 7.3% in 2002 to 41.9% in 2015 (CLI: 7.2% to 39.4%; without CLI: 7.4% to 44.2%, respectively). Of the 40.5% ( n = 4481) who were not on a statin in the year before diagnosis, 13.5% ( n = 607) newly initiated therapy within 1 month (CLI: 10.1% ( n = 150); without CLI: 15.3% ( n = 457)). Following diagnosis, 12.5% ( n = 660) discontinued statin therapy within 1 year (CLI: 15.5% ( n = 202); without CLI: 11.5% ( n = 458)). Although use of statins increased from 2002 to 2015, a substantial proportion of the overall PAD and CLI subpopulation remained untreated with statins, representing a significant treatment gap in a population at high risk for cardiovascular events and adverse limb outcomes.

Background The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline includes recommendations for intensive lipid-lowering therapy in patients at very high risk for atherosclerotic cardiovascular disease (ASCVD) events. Objectives This study sought to estimate event rates among adults with a history of ASCVD who met and did not meet the definition of very high risk in the 2018 AHA/ACC cholesterol guideline. Methods Data from U.S. adults with health insurance in the MarketScan database who had a history of ASCVD on January 1, 2016 (n = 27,775) were analyzed. Very high risk for ASCVD events was defined as a history of ≥2 major ASCVD events or 1 event and ≥2 high-risk conditions. Patients were followed through December 31, 2017, for ASCVD events, including myocardial infarction, ischemic stroke, and major adverse limb events. Results Overall, 15,366 patients (55.3%) with ASCVD met the definition of very high risk. Among patients with and without very high risk, the ASCVD event rate per 1,000 person-years was 53.1 (95% confidence interval [CI]: 50.1 to 56.1) and 17.0 (95% CI: 15.2 to 18.9), respectively. Among patients with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions, the ASCVD event rate per 1,000 person-years was 89.8 (95% CI: 82.2 to 98.0) and 41.3 (95% CI: 38.3 to 44.4), respectively. The age- and sex-adjusted hazard ratios for ASCVD events among patients with very high risk, overall, with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions versus those without very high risk were 2.98 (95% CI: 2.63 to 3.37), 4.89 (95% CI: 4.22 to 5.66), and 2.33 (95% CI: 2.04 to 2.66), respectively. Conclusions The 2018 AHA/ACC cholesterol guideline directs intensive lipid-lowering therapy to adults with a very high ASCVD event rate.

Background: Among people with ASCVD, those with T2D have excess CVD risk and derive greater absolute benefit from CVD risk reduction therapies. We describe the use of evidence-based therapies for secondary prevention in participants (pts) with T2D. Methods: We report a registry to longitudinally describe LDL-C treatment patterns among U.S. pts with ASCVD and LDL-C ≥70mg/dL taking lipid-lowering therapy. Pts (n=5006) were enrolled in 1 of 3 cohorts: taking PCSK9i (11%); LDL-C 70-99mg/dL (53%); and LDL-C ≥100mg/dL (36%). Results: Overall, 1655 (33%) had diabetes (96% with T2D): 146 in the PCSK9i cohort, 874 in the LDL-C 70-99mg/dL cohort, and 635 in the LDL-C ≥100mg/dL cohort. Mean age among pts with diabetes was 68 y, 60% were male, 81% had CAD (including 33% with prior MI), 17% with PAD, and 17% had HF. Mean LDL-C was 100mg/dL. Although overall statin use was at 87%, high-intensity statins were used in only 45% and ezetimibe in only 9.5% of pts. Aspirin and ACE-I/ARB were each used in 72% and beta blockers in 71% of pts. The most commonly used glucose-lowering medications among patients with T2D were metformin (56%), insulin (34%), and sulfonylurea (22%). Only 10% and 8% of pts with T2D were treated with SGLT2i or GLP-1RA, respectively. The proportion of pts with T2D that were receiving all guideline-recommended therapies for optimal risk reduction (high-intensity statins, aspirin, ACE-I/ARB, and either SGLT2i or GLP-1RA) was just 3%. Conclusion: In GOULD, among pts with T2D, ASCVD, and LDL-C ≥70mg/dL, most are not receiving high intensity statin therapy at baseline and few receive ezetimibe. Furthermore, less than 20% are treated with glucose-lowering therapies that have a proven CVD benefit, and a strikingly low proportion receive all guideline-recommended risk reduction strategies. These results highlight an opportunity to improve care and outcomes. Disclosure M.N. Kosiborod: Consultant; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eisai Co., Ltd., GlaxoSmithKline plc., Glytec, LLC, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis AG, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. J. De Lemos: Other Relationship; Self; Amgen Inc., Novo Nordisk A/S, Regeneron Pharmaceuticals. R.S. Rosenson: Consultant; Self; CVS/Caremark, Regeneron Pharmaceuticals. Research Support; Self; Akcea Therapeutics, Amgen Inc., Medicines Company, Regeneron Pharmaceuticals. Other Relationship; Self; Amgen Inc., Kowa Pharmaceutical Europe Co. Ltd. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Esperion, Gilead Sciences, Inc., Matinas BioPharma, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., Esperion, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Other Relationship; Self; Roche Diagnostic USA. K. Philip: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. Y. Liu: None. K.E. Mues: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. S. Alam: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. M. Elliott: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. D.L. Bhatt: Research Support; Self; Abbott, Amarin Corporation, Amgen Inc., AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Chiesi USA, Inc., Eisai Inc., Eli Lilly and Company, Ethicon, Inc., FlowCo, Forest Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Inc., Ischemix, Medicines Company, Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma, Regeneron Pharmaceuticals, Roche Pharma, Sanofi, Synaptic, Takeda Pharmaceutical Company Limited. C.P. Cannon: Consultant; Self; Alnylam, Amarin Corporation, Amgen Inc., Corvia Medical, Inc., Eisai Inc., Kowa Pharmaceutical Europe Co. Ltd., Pfizer Inc., Regeneron Pharmaceuticals, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Funding Amgen Inc.

PURPOSE: Determine the risk for cardiovascular disease (CVD) events among adults with clinically evident CVD who meet the inclusion criteria for the FOURIER clinical trial on PCSK9 inhibition in a real-world database. METHODS: We analyzed data from 2,072 African-American and 2,972 white REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants 45-85 years of age with clinically evident CVD. Study participants meeting the FOURIER inclusion criteria (one major or two minor cardiovascular risk factors, fasting LDL cholesterol ≥70 mg/dL or non-HDL cholesterol ≥100 mg/dL, triglycerides ≤400 mg/dL, and taking statin) were followed for CVD events (myocardial infarction, stroke, coronary revascularization and CVD death) from baseline in 2003-2007 through 2014. RESULTS: Overall, 771 (37.2%) African Americans and 1,200 (40.4%) whites met the FOURIER inclusion criteria. The CVD event rate per 1,000 person-years was 60.6 (95%CI 53.6-67.6) among African Americans and 63.5 (95%CI 57.7-69.3) among whites. The risk for CVD events among adults meeting the FOURIER inclusion criteria was higher for those with a history of multiple cardiovascular events (hazard ratios among African Americans and whites 1.34 [95%CI 1.05-1.71] and 1.34 [1.10-1.63], respectively), a prior coronary revascularization (1.44 [1.13-1.84] and 1.23 [1.00-1.52], respectively), diabetes (1.38 [1.08-1.76] and 1.41 [1.15-1.72], respectively), reduced glomerular filtration rate (1.63 [1.26-2.11] and 1.29 [1.03-1.62], respectively) and albuminuria (1.77 [1.37-2.27] and 1.33 [1.07-1.65], respectively). CONCLUSIONS: The CVD event rate is high among African Americans and whites meeting the FOURIER inclusion criteria. Characteristics associated with a higher CVD risk may inform the decision to initiate PCSK9 inhibition.

IMPORTANCE: Guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) recommend intensive statin therapy and adding nonstatin therapy if low-density lipoprotein cholesterol (LDL-C) levels are 70 mg/dL or more. Compliance with guidelines is often low. OBJECTIVE: To track LDL-C treatment patterns in the US over 2 years. DESIGN, SETTING, AND PARTICIPANTS: GOULD is a prospective observational registry study involving multiple centers. Patients with ASCVD receiving any lipid-lowering therapy (LLT) were eligible. Between December 2016 and July 2018, patients were enrolled in 1 of 3 cohorts: (1) those currently receiving proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) and 2 groups not receiving PCSK9i drugs, with (2) LDL-C levels of 100 mg/dL or more or (3) LDL-C levels of 70 to 99 mg/dL. Patients had medical record reviews and telephone interviews every 6 months. Analysis was done on data collected as of October 5, 2020. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in LLT use in 2 years. Secondary outcomes included the number of LDL-C measurements, LDL-C levels, and responses to structured physician and patient questionnaires over 2 years. RESULTS: A total of 5006 patients were enrolled (mean [SD] age, 67.8 [9.9] years; 1985 women [39.7%]; 4312 White individuals [86.1%]). At 2 years, 885 (17.1%) had LLT intensification. In the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, LLT intensification occurred in 403 (22.4%) and 383 (14.4%), respectively; statins were intensified in 115 (6.4%) and 168 (6.3%), ezetimibe added in 123 (6.8%) and 118 (4.5%), and PCSK9i added in 114 (6.3%) and 58 (2.2%), respectively. In the PCSK9i cohort, 508 of 554 (91.7%) were still taking PCSK9i at 2 years. Lipid panels were measured at least once over 2 years in 3768 patients (88.5%; PCSK9i cohort, 492 [96.1%]; LDL-C levels ≥100 mg/dL or more, 1294 [85.9%]; 70-99 mg/dL, 1982 [88.6%]). Levels of LDL-C fell from medians (interquartile ranges) of 120 (108-141) mg/dL to 95 (73-118) mg/dL in the cohort with LDL-C levels of 100 mg/dL or more, 82 (75-89) to 77 (65-90) mg/dL in the cohort with LDL-C levels of 70 to 99 mg/dL, and 67 (42-104) mg/dL to 67 (42-96) mg/dL in the PCSK9i cohort. Levels of LDL-C less than 70 mg/dL at 2 years were achieved by 308 patients (21.0%) and 758 patients (33.9%) in the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, respectively, and 272 patients (52.4%) in the PCSK9i cohort. At 2 years, practice characteristics were associated with more LLT intensification (teaching vs nonteaching hospitals, 148 of 589 [25.1%] vs 600 of 3607 [16.6%]; lipid protocols or none, 359 of 1612 [22.3%] vs 389 of 2584 [15.1%]; cardiology, 452 of 2087 [21.7%] vs internal or family medicine, 204 of 1745 [11.7%] and other, 92 of 364 [25.3%]; all P

Rationale & Objective The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline uses risk stratification to guide the decision to initiate nonstatin lipid-lowering medication among adults with atherosclerotic cardiovascular disease (CVD). We determined atherosclerotic CVD (ASCVD) event rates among adults with chronic kidney disease (CKD) taking statin therapy within 2018 AHA/ACC cholesterol guideline risk categories. Study Design Observational cohort study. Setting & Participants Adults with CKD not on dialysis in the Chronic Renal Insufficiency Cohort (CRIC) study who were taking a moderate/high-intensity statin 1 year after enrollment (baseline for the current analysis, n = 1,753). Exposure 2018 AHA/ACC cholesterol guideline risk categories: without a history of ASCVD, a history of 1 major ASCVD event and multiple high-risk conditions, and a history of ≥2 major ASCVD events. Outcome Adjudicated ASCVD events after the year 1 study visit. Analytical Approach We calculated age-sex standardized rates for ASCVD events and age-sex adjusted hazard ratios for ASCVD events accounting for the competing risk of death. Results There were 394 ASCVD events over a median follow-up period of 8 years. The ASCVD event rates (with 95% CI) per 1,000 person-years among participants without a history of ASCVD, with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 21.7 (18.4-25.1), 45.0 (37.8-52.3), and 73.3 (53.3-93.4), respectively. Compared with participants without a history of ASCVD, the HR (95% CI) rates for ASCVD events among those with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 1.89 (1.52-2.36) and 2.50 (1.85-3.39), respectively. Limitations Data on whether participants were taking a maximally tolerated statin dosage were unavailable. Conclusions The 2018 AHA/ACC cholesterol guideline identifies adults with CKD who have very high ASCVD risk despite taking a moderate/high-intensity statin., Graphical abstract

Background The 2013 American College of Cardiology/American Heart Association cholesterol guidelines recognize cardiovascular disease and diabetes mellitus but not chronic kidney disease ( CKD ) as high‐risk conditions warranting statin therapy. Statin use may be lower for adults with CKD compared with adults with conditions that have guideline indications for statin use. Methods and Results We analyzed data from the National Health and Nutrition Examination Surveys from 1999–2002 through 2011–2014 to determine trends in the percentage of US adults ≥20 years of age with and without CKD taking statins. CKD was defined by an estimated glomerular filtration rate 2 or albumin‐to‐creatinine ratio ≥30 mg/g. Statin use was identified through a medication inventory. Between 1999–2002 and 2011–2014, the percentage of adults taking statins increased from 17.6% to 35.7% among those with CKD and from 6.8% to 14.7% among those without CKD . After multivariable adjustment, adults with CKD were not more likely to be taking statins compared with those without CKD (prevalence ratio, 1.01; 95% CI] 0.96–1.08). Among adults without a history of cardiovascular disease, those with CKD but not diabetes mellitus were less likely to be taking statins compared with those with diabetes mellitus but not CKD (prevalence ratio, 0.54; 95% CI , 0.44–0.66). Among adults with a history of cardiovascular disease, there was no difference in statin use between those with CKD but not diabetes mellitus versus those with diabetes mellitus but not CKD (prevalence ratio, 0.95; 95% CI , 0.79–1.15). Conclusions CKD does not appear to be a major stimulus for statin use among US adults.

Background Prior studies suggest that persistence with and adherence to statin therapy is low. Interventions to improve statin persistence and adherence have been developed over the past decade. Methods and Results This was a retrospective cohort study of adults aged ≥21 y with commercial or government health insurance in the MarketScan (Truven Health Analytics) and Medicare databases who initiated statins in 2007–2014 and (1) started treatment after a myocardial infarction (n=201 573), (2) had diabetes mellitus but without coronary heart disease (CHD; n=610 049), or (3) did not have CHD or diabetes mellitus (n=2 244 868). Persistence with (ie, not discontinuing treatment) and high adherence to statin therapy were assessed using pharmacy fills in the year following treatment initiation. In 2007 and 2014, the proportions of patients persistent with statin therapy were 78.1% and 79.1%, respectively, among those initiating treatment following myocardial infarction; 66.5% and 67.3%, respectively, for those with diabetes mellitus but without CHD; and 64.3% and 63.9%, respectively, for those without CHD or diabetes mellitus. Between 2007 and 2014, high adherence to statin therapy increased from 57.9% to 63.8% among patients initiating treatment following myocardial infarction and from 34.9% to 37.6% among those with diabetes mellitus but without CHD (each P trend P trend =0.14). In 2014, statin adherence was lower among younger, black, and Hispanic patients versus white patients and those initiating a high‐intensity statin dosage. Statin adherence was higher among men and patients with cardiologist care following treatment initiation. Conclusions Persistence with and adherence to statin therapy remain low, particularly among those without CHD.

Katherine E Mues,1 Alina N Bogdanov,2 Keri L Monda,1 Larisa Yedigarova,3 Alexander Liede,1 Lee Kallenbach2 1Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA; 2Practice Fusion, San Francisco, CA,USA; 3US Medical Affairs, Amgen Inc., Thousand Oaks, CA, USA Background: Familial hypercholesterolemia (FH) is a condition characterized by high cholesterol levels and increased risk for coronary heart disease (CHD) that often goes undiagnosed. The Dutch Lipid Network Criteria (DLNC) are used to identify FH in clinical settings via physical examination, personal and family history of CHD, in addition to the presence of deleterious mutations of the LDLR, ApoB, and PCSK9 genes. Agreement between clinical and genetic diagnosis of FH varies. While an ICD diagnosis code was not available for coding FH until 2016, Systematized Nomenclature of Medicine (SNOMED) clinical concept codes, including genetic diagnoses, for FH have been utilized in electronic health records (EHRs). Objective: To evaluate the concordance of identifying FH via SNOMED and ICD-10 CM codes vs the DLNC in an EHR database. Methods: Using the Practice Fusion EHR database, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated comparing an FH cohort identified via SNOMED and ICD-10 CM codes to one identified via the DLNC. Results: Among 907,616 patients with hypercholesterolemia, 2,180 were identified as FH via SNOMED code (zero were identified via ICD-10 CM), 259 had a DLNC score 6–8 (probable FH), and 45 had a DLNC score >8 (definite FH). Compared to DLNC score >8, the sensitivity, specificity, and PPV of the FH SNOMED code were 84.4%, 99.4%, and 6.4%, respectively. Compared to DLNC score ≥6, the sensitivity was 36.8% and the specificity was 99.5% with a PPV of 18.7%. Conclusion: Compared to the clinical criteria for FH, identification of FH patients via SNOMED diagnosis codes had high sensitivity and specificity, but low PPV. The discordance of these two techniques in identifying FH patients speaks to the challenges in identifying FH patients in large electronic databases such as administrative claims and EHR. Keywords: familial hypercholesterolemia, Dutch Lipid Network Criteria, electronic health record, SNOMED

Background: Statins are effective for the primary and secondary prevention of coronary heart disease (CHD) events. However, studies from the early 2000s have suggested that many patients have low adherence to statin therapy. Objective: To analyze trends in adherence among US adults initiating treatment with a statin. Methods: We identified US adults 21-64 years of age with commercial health insurance in Marketscan and ≥65 years of age with government health insurance through Medicare who initiated statin therapy in 2007-2014. Three populations were analyzed, those initiating statin therapy 1) following myocardial infarction (n=52,828 in Marketscan, n=148,745 in Medicare), 2) with diabetes without a history of CHD (n=565,573 in Marketscan, n=42,411 in Medicare), and 3) without diabetes or a history of CHD (n=2,134,501 in Marketscan, n=105,948 in Medicare). Adherence to statin therapy was defined by having a statin available to take for ≥80% of the 365 days following treatment initiation. Results: Adherence to statin therapy increased in each population analyzed ( Figure ). In 2014, 68.1% and 62.7% of patients initiating treatment following myocardial infarction in Marketscan and Medicare, respectively were adherent to their statin. Less than half of patients initiating treatment with diabetes without CHD and without diabetes or CHD in Marketscan and Medicare were adherent to their statin. Adherence to statin therapy in the overall Marketscan and Medicare populations was higher among men (relative risk [95% CI] 1.16 [1.15, 1.18] and 1.10 [1.08, 1.12], respectively), and those with cardiologist visits (1.22 [1.21, 1.24] and 1.27 [1.25, 1.30], respectively), and lower among those with kidney disease diagnosed after treatment initiation (0.89 [0.85, 0.94] and 0.92 [0.88, 0.96], respectively). Conclusion: Adherence to statins improved slightly between 2007 and 2014 but remains suboptimal. Management by a cardiologist is associated with better adherence to statins.

Proprotein convertase subtilisin/kexin type 9 inhibitor antibodies (PCSK9i) have been shown prevent cardiovascular disease events in patients with atherosclerotic cardiovascular disease (ASCVD). Analyzing the characteristics of patients who initiate and do not initiate a PCSK9i may identify

Lipid control is a key pillar of secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD). Prior analyses have shown suboptimal use of high intensity statins, even among the highest risk patients with ASCVD (e.g., diabetes, prior MI). We surveyed patients with ASCVD and

Background Nutrition rehabilitation centers (NRCs) have shown mixed results in reducing morbidity and mortality among undernourished children in the developing world. Follow-up on children after leaving these programs remains undocumented. Objective To assess the nutritional improvement of children attending the Centro de Rehabilitación Infantil Nutricional (CRIN), a residential NRC in rural Bolivia, from entrance to exit and to a household follow-up visit 1 month to 6 years later, and to identify factors associated with nutritional improvement. Methods A retrospective analysis was conducted of clinical records collected by CRIN staff from 135 children under 3 years of age attending CRIN in rural Cochabamba, Bolivia, from 2003 to 2009, and of clinical records of household follow-up measurements on a subset of 26 children that were taken between 1 month and 6 years postexit. Nutritional status was evaluated by calculating z-scores for weight-for-height (WHZ), weight-for-age (WAZ), and height-for-age (HAZ). Children with z-scores < −2 were considered to be wasted, underweight, or stunted, respectively. Results The prevalence of wasting decreased significantly, while the prevalence of stunting did not change significantly between entrance and exit from the program. From entrance to exit, the mean changes in WHZ (0.79) and WAZ (1.08) were statistically significant, while the mean change in HAZ (–0.02) was not significant. Linear regression analysis suggested that nutritional status and diarrhea at entrance had the greatest effect on WHZ and HAZ changes between entrance and exit. Children maintained their nutritional gains from the program between exit and follow-up and showed statistically significant improvement in WAZ (but not HAZ). Conclusions CRIN is effective at rehabilitating nutritional deficits associated with wasting, but not those associated with stunting.

GeoSentinel is a global surveillance network of travel medicine clinics that collect data from ill international travelers. Analyses have relied on proportionate morbidity calculations, but proportionate morbidity cannot estimate disease risk because healthy travelers are not included in the denominator. The authors evaluated the use of a case-control design, controlling for GeoSentinel site and date of clinic visit, to calculate a reporting odds ratio (ROR). The association between region of travel and acute gastrointestinal illness was evaluated. All analyses found that the association with acute gastrointestinal illness was greatest among those who traveled to North Africa and South-Central Asia. There was consistency in the magnitude of the ROR and proportionate morbidity ratio (PMR) in regions such as the Caribbean. However, in other regions, the matched ROR was noticeably different than the PMR. The case-control ROR may be preferred for single-disease/syndrome analytical studies using GeoSentinel surveillance data or other surveillance data.

OBJECTIVE: To assess factors influencing perspectives on Brazil's national Family Health Program (PSF) by exploring satisfaction with PSF units and home-visit community health agents and perceptions about PSF unit accessibility among frequent users (primary caretakers of children under age 5) in Vespasiano, Minas Gerais. METHODS: Data were collected though cross-sectional household surveys to determine pro grammatic and demographic factors affecting user satisfaction with the PSF. Multivariate logistic modeling was used to estimate users' satisfaction with PSF units and agents and perceived access to PSF unit services. Chi-square and analysis of variance (ANOVA) tests were used to estimate statistical differences. RESULTS: The majority of caretakers were satisfied with both their PSF unit and their PSF community health agent and had received at least one monthly home visit from the health agent. Satisfaction with both the health agent and the unit was positively associated with per ceived access to the unit and frequency of agent home visits. Caretakers who reported that their PSF agent made one or more home visits per month were more likely to perceive the PSF unit as being "accessible" (or "sometimes accessible"). CONCLUSIONS: The current data are important indicators of population health in Minas Gerais, Brazil, and suggest that users' satisfaction with the PSF and perceptions about its accessibility can be improved by ensuring that all households receive at least one health agent home visit per month. These results could be applied to other parts of Brazil or Latin America to improve understanding of user perceptions of health systems.OBJETIVO: Evaluar los factores que influyen en las perspectivas sobre el Programa de Salud Familiar (PSF) del Brasil, mediante el análisis de la satisfacción de los usuarios frecuentes del PSF (cuidadores primarios de niños menores de 5 años) con las unidades y los agentes de salud comunitarios que efectúan las visitas a domicilio, y de la percepción de dichos usuarios respecto de la accesibilidad a la unidad del PSF en Vespasiano, Minas Gerais. MÉTODOS: Se recopilaron datos mediante encuestas transversales de hogares para determinar los factores programáticos y demográficos que afectaban la satisfacción de los usuarios con el PSF. Para estimar la satisfacción de los usuarios con las unidades y los agentes de salud del PSF y su percepción sobre el acceso a los servicios prestados por la unidad del PSF se usó un modelo logístico multifactorial. Para calcular las diferencias estadísticas se usaron las pruebas de ji al cuadrado y análisis de la varianza (ANOVA). RESULTADOS: La mayoría de los cuidadores estuvieron satisfechos tanto con su unidad del PSF como con su agente de salud comunitario del programa, de quien habían recibido al menos una visita a domicilio mensual. La satisfacción con este y con la unidad se asoció positivamente con la percepción de acceso a la unidad y con la frecuencia de las visitas a domicilio del agente. Los cuidadores que informaron que su agente del PSF hizo una o más visitas al domicilio por mes presentaron mayores probabilidades de considerar a la unidad del PSF como "accesible" (o "a veces accesible"). CONCLUSIONES: Los datos actuales son indicadores importantes del estado de salud de la población en Minas Gerais, Brasil, y sugieren que la satisfacción de los usuarios con el PSF y su percepción acerca de la accesibilidad a este pueden mejorarse si se garantiza que todos los hogares reciban al menos una visita a domicilio mensual del agente de salud. Estos resultados podrían aplicarse a otras zonas del Brasil o de América Latina para comprender mejor la percepción de los usuarios sobre los sistemas de salud.

OBJECTIVE: To assess factors influencing perspectives on Brazil's national Family Health Program (PSF) by exploring satisfaction with PSF units and home-visit community health agents and perceptions about PSF unit accessibility among frequent users (primary caretakers of children under age 5) in Vespasiano, Minas Gerais. METHODS: Data were collected though cross-sectional household surveys to determine pro grammatic and demographic factors affecting user satisfaction with the PSF. Multivariate logistic modeling was used to estimate users' satisfaction with PSF units and agents and perceived access to PSF unit services. Chi-square and analysis of variance (ANOVA) tests were used to estimate statistical differences. RESULTS: The majority of caretakers were satisfied with both their PSF unit and their PSF community health agent and had received at least one monthly home visit from the health agent. Satisfaction with both the health agent and the unit was positively associated with per ceived access to the unit and frequency of agent home visits. Caretakers who reported that their PSF agent made one or more home visits per month were more likely to perceive the PSF unit as being "accessible" (or "sometimes accessible"). CONCLUSIONS: The current data are important indicators of population health in Minas Gerais, Brazil, and suggest that users' satisfaction with the PSF and perceptions about its accessibility can be improved by ensuring that all households receive at least one health agent home visit per month. These results could be applied to other parts of Brazil or Latin America to improve understanding of user perceptions of health systems.

Despite national cholesterol treatment guidelines, many patients with atherosclerotic cardiovascular disease (ASCVD) do not receive guideline-recommended therapy. In the multicenter, observational Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia

During the 2008 Olympic and Paralympic Games, we conducted surveillance of illnesses among travelers at six Beijing clinics. Surveys asked about demographic, pre-travel, and vaccination information, and physician-provided diagnoses. Of 807 respondents, 38% and 57% were classified as foreign visitors (FV) and expatriates, respectively. Less than one-half of FV sought pre-travel advice; sources included health-care providers and friends/family. FV vaccination rate was also low; however, most vaccines given were recommended by the Centers for Disease Control and Prevention. The most common FV diagnoses were respiratory, injury/musculoskeletal, and gastrointestinal illnesses; for expatriates, injury/musculoskeletal, respiratory, and dermatologic were the most common illnesses. Respiratory illnesses in expatriates were significantly less in 2008 than during 2004-2007 (chi(2) = 10.2; P = 0.0014), suggesting that control programs may have reduced pollutants/respiratory irritants during the 2008 Games. We found no previous studies of health outcomes among expatriates living in cities with mass travel events. These findings highlight the need to continuously disseminate information to health-care providers advising travelers.

Clinical trials in atherosclerotic cardiovascular disease (ASCVD) patients have shown that high-intensity statin effectively reduces CV events. In high-risk patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL, adding a second LDL-C agent to statin therapy further reduces CVD events

Episodes of adenolymphangitis (ADL) are a recurrent clinical aspect of lymphatic filariasis (LF) and a risk factor for progression of lymphedema. Inter-digital entry lesions, often found on the web spaces between the toes of those suffering from lymphedema, have been shown to contribute to the occurrence of ADL episodes. Use of antifungal cream on lesions is often promoted as a critical component of lymphedema management. Our objective was to estimate the observed effect of antifungal cream use on ADL episodes according to treatment regimen among a cohort of lymphedema patients enrolled in a morbidity management program. We estimated this effect using marginal structural models for time varying confounding. In this longitudinal study, we estimate that for every one-unit increase in the number of times one was compliant to cream use through 12 months, there was a 23% (RR = 0.77 (0.62, 0.96)) decrease in the number of ADL episodes at 18 months, however the RR’s were not statistically significant at other study time points. Traditionally adjusted models produced a non-significant RR closer to the null at all time points. This is the first study to estimate the effect of a regimen of antifungal cream on the frequency of ADL episodes. This study also highlights the importance of the consideration and proper handling of time-varying confounders in longitudinal observational studies.

Background Lymphedema management programs have been shown to decrease episodes of adenolymphangitis (ADLA), but the impact on lymphedema progression and of program compliance have not been thoroughly explored. Our objectives were to determine the rate of ADLA episodes and lymphedema progression over time for patients enrolled in a community-based lymphedema management program. We explored the association between program compliance and ADLA episodes as well as lymphedema progression. Methodology/Principal Findings A lymphedema management program was implemented in Odisha State, India from 2007–2010 by the non-governmental organization, Church's Auxiliary for Social Action, in consultation with the Centers for Disease Control and Prevention. A cohort of patients was followed over 24 months. The crude 30-day rate of ADLA episodes decreased from 0.35 episodes per person-month at baseline to 0.23 at 24 months. Over the study period, the percentage of patients who progressed to more severe lymphedema decreased (P-value = 0.0004), while those whose lymphedema regressed increased over time (P-value, Author Summary Lymphatic filariasis (LF) is characterized by clinical manifestations of limb swelling, lymphedema, and elephantiasis. LF is the world's second-leading cause of disability, with up to 15 million people with limb lymphedema or elephantiasis. The Global Programme to Eliminate LF aims to eliminate the disease through two pillars: (1) interruption of transmission and (2) treatment of clinical disease among those already affected. The Church's Auxiliary for Social Action (CASA), an Indian NGO, began a lymphedema management program in Khurda District, Odisha State, India in 2007. We evaluated the impact of the program on two clinical LF outcomes: acute episodes of adenolymphangitis (ADLA) and chronic lymphedema progression. The monthly rate of ADLA episodes decreased significantly after enrollment for two years in the program. Additionally, program compliance was found to be associated with ADLA rate among some clinically distinct groups. Compliance to soap was associated with a decreased rate of ADLA episodes among those without inter-digital entry lesions. The percentage of patients who progressed to more severe lymphedema decreased significantly over time, while those whose lymphedema regressed increased significantly. These results indicate that a community-based lymphedema management program is beneficial for lymphedema patients for both ADLA episodes and lymphedema. It is one of the first studies to demonstrate an association between program compliance and ADLA episodes.

Background Lymphatic filariasis (LF) infects approximately 120 million people worldwide. As many as 40 million have symptoms of LF disease, including lymphedema, elephantiasis, and hydrocele. India constitutes approximately 45% of the world's burden of LF. The Indian NGO Church's Auxiliary for Social Action (CASA) has been conducting a community-based lymphedema management program in Orissa State since 2007 that aims to reduce the morbidity associated with lymphedema and elephantiasis. The objective of this analysis is to evaluate the effects of this program on lymphedema patients' perceived disability. Methodology/Principal Findings For this prospective cohort study, 370 patients ≥14 years of age, who reported lymphedema lasting more than three months in one or both legs, were recruited from villages in the Bolagarh sub-district, Khurda District, Orissa, India. The World Health Organization Disability Assessment Schedule II was administered to participants at baseline (July, 2009), and then at regular intervals through 24 months (July, 2011), to assess patients' perceived disability. Disability scores decreased significantly (p, Author Summary Lymphatic filariasis (LF) is the world's second-leading cause of disability and causes limb lymphedema and elephantiasis in up to 15 million people and lymphedema or hydrocele in over 40 million people, worldwide. A massive global effort has been undertaken to eliminate LF as a public health problem. LF elimination is based on two pillars: (1) interruption of transmission and (2) treatment of clinical disease among those already affected. The Indian NGO, Church's Auxiliary for Social Action (CASA), has been providing community-based treatment of lymphedema in Khurda District, Orissa State, India, since 2007. We evaluated the impact of this treatment program on the participating patients' perceived disability using the WHO Disability Assessment Schedule II (WHO-DAS II). After two years of enrollment in the program, patients had significantly lower levels of perceived disability. We found that being employed and time enrolled in the program were associated with significant reductions in disability scores. Compared to baseline, patients enrolled in the program for at least 12 months reported 2.5 fewer days of work lost in the previous 30 days due to their lymphedema. These findings indicate that participation in a community-based lymphedema management program can reduce patients' disability and prevent days of work lost due to lymphedema.