High-intensity Statin Use Research Articles

Abstract 17323: Personalizing Cholesterol Management Therapy Using Electronic Medical Records and Machine Learning

Introduction: Optimal statin treatment decisions for primary prevention of atherosclerotic cardiovascular disease (ASCVD) rely on shared decision-making between patient and provider. We sought to develop a machine learning-based algorithm to personalize cholesterol treatment decisions using electronic medical record (EMR) data. Methods: We included EMR data for adults aged 40 to 79 with no prior ASCVD or statin therapy from an outpatient Northern California system between January 1, 2009 and December 31, 2018 with at least two visits at least 1 year apart and at least two low density lipoprotein cholesterol (LDL-C) values. The outcome was the LDL-C measured closest to one year after a patient’s second visit. We modeled four different treatment decisions: no statin use, low-intensity statin use, moderate-intensity statin use, and high-intensity statin use. We trained weighted-K-nearest-neighbor (wKNN) regression models to identify similar patients using each line of therapy to a candidate patient. The algorithm compared outcomes of these similar patients and recommended the treatment which predicted the lowest LDL-C after one year. Results: Our study cohort consisted of 50,911 patients (age 54.6 ± 9.84 years, baseline LDL-C 122 ± 34.2 mg/dL, follow-up LDL-C 121 ± 35.9 mg/dL) including 54% female, 47% Non-Hispanic White, 32% Asian, and 7.5% Hispanic patients. Among 8,551 test patients visiting in 2015 or later, 96.9%, 3.08%, and 0.05% were recommended to begin high-intensity, moderate-intensity, and low-intensity statins, respectively. With these recommendations, the LDL-C values at 1-year follow-up were predicted to be 21.5 ± 43.5 mg/dL (17.6%) lower per patient, on average (Figure). Conclusions: EMR-trained wKNN models are able to determine patient LDL-C trajectories under different lines of statin therapy. Machine learning models leveraging real-world datasets may provide useful statin therapy treatment recommendations for primary ASCVD prevention.

Recommendations and associated levels of evidence for statin use in primary prevention of cardiovascular disease: a comparison at population level of the ESC, ACC/AHA, USPSTF, and CCS Guidelines

Abstract Background It is unclear to what extent the 2019 European Society of Cardiology (ESC), 2018 American College of Cardiology/ American Heart Association (ACC/AHA), 2016 US Preventive Services Task Force (USPSTF), and 2016 Canadian Cardiovascular Society (CCS) guidelines differ in assigning levels of evidence and classes of recommendations (LOE/class) to lipid-lowering treatment recommendations in primary prevention of cardiovascular disease (CVD). Purpose To compare LOE/class from four commonly used guidelines at population level. Methods A total of 7262 participants, aged 45–75 years of age and without history of CVD, from the prospective population-based Rotterdam Study were included. Per guideline, proportions of the population recommended statin therapy by LOE/class, sensitivity and specificity, and numbers needed to treat at 10 years (NNT10y) were calculated. Results Mean age was 61.1 (SD 6.9) years, and 58.2% were women. ESC, ACC/AHA, USPSTF and CCS strongly recommended statin use for a respective 33.8%, 48.1%, and 40.2% and 73.0% of the eligible population based on high-quality evidence, while in an additional 55.3%, 7.1%, 8.4% and 9.2% of participants statins use could or should be considered based on varying LOE/class. The sensitivity for treatment recommendations supported with strong, high quality evidence was 61.6% for ESC (“IA”), 74.6% for ACC/AHA (“IA or IB”), 69.4% for USPSTF (“USPSTF-B”) and 92.5% for CCS (“strong”). Specificity was highest for the ACC/AHA at 46.8% and lowest for ESC at 11.4%. Estimated NNT10y for those with the strongest LOE/class were comparable across all guidelines, ranging from 18 to 26 for moderate-intensity statin use, and 11 to 16 for high-intensity statin use. NNT10y reflective of recommendations supported with moderate strength of LOE/class varied substantially among guidelines for both moderate-intensity and high-intensity statin use, ranging from 33 for ESC and USPSTF to 91 for CCS. Conclusions Assigned LOE/class varied greatly among four clinical practice guidelines for primary prevention of CVD. Efforts for harmonized and comparable evidence grading system for clinical practice guidelines in primary prevention of CVD may reduce ambiguity, and reinforce updated evidence-based recommendations for appropriate treatment of populations for whom clear evidence for benefit of statin use is available. Funding Acknowledgement Type of funding source: None

A longitudinal evaluation of cardiovascular risk factors, treatment patterns, and outcomes in patients with documented cardiovascular disease treated with lipid lowering therapy in the United Kingdom

Abstract Background Over time, guidelines for dyslipidemia management in patients at high risk of atherosclerotic cardiovascular disease (CVD) changed with the goal of improving patient outcomes. Guidelines have been released by the European Joint Task Force in 2007, 2012 and 2016, European Society of Cardiology in 2011, 2016 and 2019, Joint British Societies in 2014, and National Institute for Health and Care Excellence in 2014. Purpose Evaluate cardiovascular risk factors, treatment patterns, and cardiovascular outcomes over time related to dyslipidemia management. Methods Ten prevalent cohorts of patients with documented CVD receiving lipid-lowering therapy (LLT) were created using Clinical Research Practice Datalink (CPRD) records as of January 1, each year from 2008 through 2017. For each cohort, we identified CVD risk factors and LLT, and estimated the 1-year composite rate of fatal and nonfatal myocardial infarction (MI), ischemic stroke (IS), or revascularization. Patient follow-up was censored at the earliest of one year, end of data, or the outcome of interest. Patients in each cohort were required to be ≥18 years old, have ≥1 years of available medical history, and have received ≥2 LLT prescriptions in the prior year. Documented CVD was defined as MI, IS, angina, revascularization, transient ischemic attack, carotid stenosis, abdominal aortic aneurysm, or peripheral arterial disease. Patients could be in multiple cohorts. Results Annual patient counts ranged from 170,501 to 179,137 through 2013 and declined to 94,418 by 2017 (due to fewer patients in the overall CPRD data). Comparing 2008, 2011 (when ESC guidelines were revised) and 2017 showed the following for CVD risk factors: mean age was 71.6, 72.3, and 72.5 years; males were 59.9%, 61.1%, and 63.1%; current smoking was 15.1%, 15.2%, and 13.9%; type 2 diabetes was 18.4%, 20.2%, and 22.4%; stage 3–5 chronic kidney disease was 22.4%, 25.1%, and 22.8%; history of MI was 22.5%, 23.9%, and 27.4%; history of IS was 5.5%, 6.6%, and 7.9%; LDL <1.8 mmol/L was 27.8%, 29.2% and 37.2%; and LDL <1.4 mmol/L was 9.9%, 10.1%, and 15.6%. In terms of treatment, high intensity statin use increased from 12.9% to 15.7% to 30.8%; atorvastatin 40–80 mg use increased from 12.9% to 15.5% to 30.5%; while simvastatin 20–40 mg use decreased from 55.4% to 58.8% to 36.7%. The 1-year cardiovascular event rate declined from 2.54 to 2.35 to 1.96 events per 100 person-years (Figure). Conclusions After 2011 in the UK, there was an increased use of high intensity statins, a greater proportion of patients with LDL levels <1.8 and <1.4 mmol/L, and lower 1-year cardiovascular event rates. While improved CVD management likely contributed to the event rate decline, less than 40% of very high-risk patients achieved an LDL <1.8 mmol/L, and the proportion with LDL <1.4 mmol/L, as recommended by the 2019 ESC guidelines, was less than 20%. Clinicians should continue their efforts to reduce LDL in these patients. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

Apabetalone, a selective BET protein inhibitor, reduces ischemic cardiovascular events and hospitalization for heart failure in patients with acute coronary syndrome and type 2 diabetes

Abstract Background Despite established treatments, patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS) are at higher risk of ischemic cardiovascular (CV) events and hospitalization for heart failure (HHF) compared to those without T2DM. LDL-C lowering or use of GLP-1 agonists predominantly affects ischemic CV events, with little effect on HHF. Conversely, treatment with SGLT-2 inhibitors reduces HHF, with less effect on ischemic CV events. Preclinical studies indicate that bromodomain and extra-terminal (BET) proteins coordinate gene transcription for pathways that promote atherothrombotic events as well as heart failure. We assessed the clinical effect of apabetalone (APB), a novel BET protein inhibitor, on a composite of non-fatal ischemic CV events, HHF, and CV death in a post hoc analysis of the BETonMACE trial Methods BETonMACE was a double-blind, placebo-controlled phase 3 study in patients with T2DM and recent acute coronary syndrome receiving standard of care risk factor management. In 13 countries, 2425 patients were enrolled. We conducted a time-to-event analysis for first adjudicated CV death or non-fatal MI, stroke, or HHF using a log-rank test and Cox proportional hazards model. Results At baseline median age was 62 years, 25.6% were female, 87.6% white, and use of high intensity statin, ACE inhibitors/ angiotensin II blockers, dual antiplatelet therapy and beta blocker were 90, 88, 92 and 91% respectively. A total of 312 subjects had an endpoint event, with 139 (11.5%) patients in the ABP group and 173 (14.3%) among PBO (HR 0.78, 95% CI 0.63–0.98, p=0.03, Figure). At 26 months, the absolute risk reduction was 3.2% and number needed to treat was 31. Numerically favorable HRs were observed for each component endpoint except for stroke (Table). Conclusion This present analysis suggests that BET inhibition with APB may be a novel pathway through which to reduce both HHF and ischemic CV events in high risk patients with T2DM thus impacting broader clinical outcomes with potentially large benefits for patients and healthcare systems. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Resverlogix Corp

Consumption and market share of cholesterol-lowering drugs in high-risk patients before and after the release of the 2013 ACC/AHA cholesterol guidelines: a retrospective observational study

ObjectiveWe examined the use of cholesterol-lowering drugs in Taiwan in high-risk patients before and after the release of the 2013 American College of Cardiology and the American Heart Association (ACC/AHA)...

High risk US adults with untreated hyperlipidaemia in NHANES: estimated reduction in cardiovascular events with statin treatment

Abstract Introduction Dyslipidemia is widely prevalent. Despite guidelines that recommend statin therapy for high-risk patients, many of these patents are untreated. This gap in care must be urgently closed. Purpose We analyzed data from the National Health and Nutrition Examination Survey (NHANES) in order to: (1) ascertain the number of high-risk individuals with dyslipidaemia not receiving lipid lowering therapy in the United States; and (2) estimate the reduction in acute cardiovascular (CV) events if those individuals were treated with either moderate or high potency statins in order to achieve at minimum a 30% or 50% reduction in LDL-C levels. Methods Data from NHANES participants who had fasting blood serum data available, including lipids, were included in our analysis (n=14,888). Statistical analyses were performed in the R language. Coronary heart disease (CHD) risk was assessed using NCEP ATP III criteria, and participants were categorized as being at high, intermediate, or low CHD risk. Data from seven surveys from 2003–4 to 2015–6 was used and extrapolations to the US adult population (50 states plus the District of Columbia) were performed using the direct method to the US Census 2000 population. Results We identified 1162 adults (age 20–79) who were high-risk and untreated despite being hyperlipidaemic (LDLC ≥100mg/dL). We estimated they represent 12.8 million individuals in the US 2015–16 population. Without lipid modification and hypothecating 10-year risks of CV events in this group of 20, 25, 30, 35 and 40%, respectively, predicted numbers of CV events are 2.6M, 3.2M, 3.9M, 4.5M, and 5.1M. Moderate-intensity statins reduce LDLC by 30–40% and high-intensity statins by 50–60%. Using untreated LDL-C values from all NHANES surveys we calculated predicted absolute reductions in LDL-C would be at least 42 mg/dL if a moderate-intensity statin was used and at least 70 mg/dL if a high-intensity statin was used, with reductions in CV risk of at least 27% and 46%, respectively. In this group of untreated high-risk individuals, predicted numbers of CV events that could be prevented by moderate-intensity statin for 10 years range from at least 0.7M to at least 1.4M, and with high-intensity statin use for 10 years from at least 1.2M to at least 2.3M, depending on the level of untreated risk. With Numbers Needed to Treat (NTT) between 5 and 18, use of statin treatment in this group would be highly beneficial and cost-effective. Conclusions There are a large number of untreated high-risk individuals with dyslipidaemia in the US. Use of moderate and high dose statin therapy in these patients for 10 years would reduce CV risk by at least 27% and 47%, respectively. Among untreated high-risk patients, the NNTs for moderate and high dose statin therapy are 9–18 and 5–11, respectively, depending on 10-year level of CV risk. The quality of life and socioeconomic implications of these estimates are substantial. Funding Acknowledgement Type of funding source: None

Impact of lipid levels and high-intensity statins on vein graft patency after CABG: Midterm results of the ACTIVE trial.

High-dose atorvastatin did not improve 1-year vein graft patency in the recent Aggressive Cholesterol Therapy to Inhibit Vein Graft Events trial. However, it remains unknown whether high-intensity statins may impact graft disease in the years that follow. In the trial, patients (N = 173) were randomized to receive atorvastatin 10 or 80 mg for 1 year after coronary bypass surgery (CABG). Beyond 1 year, the choice of statin was left to the patient's physician. In this study of participants who agreed to follow-up (N = 76), low-density lipoprotein (LDL) levels were measured and graft patency was assessed 3 years after surgery. The rate of vein graft disease 3 years after surgery was not significantly reduced with atorvastatin 80 mg during the first postoperative year or the use of open-label high-intensity statin thereafter (p = NS). However, a trend was observed between higher LDL levels during the first postoperative year and a greater incidence of vein graft disease at 3 years (p = .12). Among patients who had LDL levels more than 90 mg/dl in the first year after CABG, 38.5% had vein graft disease at 3 years, compared to 19.0% for those with LDL levels less than 90 mg/dl (p = .15). Higher mean LDL levels during the first postoperative year were associated with a higher rate of vein disease 3 years after surgery both at the graft level (p = .03) and at the patient level (p = .03) in multivariate analysis. Higher LDL levels during the first postoperative year were associated with significantly greater vein graft disease 3 years after CABG.

S1423 Lipoprotein Lipase Deficiency as a Rare Cause of Acute Pancreatitis

INTRODUCTION: Hypertriglyceridemia (HTG)-induced pancreatitis comprises 1 to 14 % of all cases of acute pancreatitis. Generally, primary HTG refers to a genetic disorder that includes type 1, 4 and 5 dyslipidemia. Familial lipoprotein lipase (LPL) deficiency is a rare condition of primary HTG with autosomal recessive transmission and a prevalence of 1-2:1,000,000. This case describes a patient with acute pancreatitis attributed secondary to LPL deficiency. CASE DESCRIPTION/METHODS: A 28 year old female with a history of type 1 diabetes mellitus complicated by diabetic gastroparesis s/p gastrojejunal bypass, HTN, HTG, recurrent pancreatitis presented to ED with abdominal pain. She had numerous admissions in the past due to recurrent pancreatitis secondary to HTG , one of which was complicated by necrotizing pancreatitis and wall off necrosis for which she underwent partial pancreatectomy. The patient also has an extensive family history of early onset type 1 diabetes and HTG. Despite the use of high intensity statin, fenofibrate, diet restriction and insulin pump, triglyceride levels has been very difficult to control. On physical examination, multiple red-yellowish bumps are noted on the arms consistent with xathomas. Labs were significant for elevated triglycerides and lipase (4500 and 400 respectively). Abdomen and pelvis CT scan showed evidence suggestive of acute pancreatitis, splenic vein thrombosis and hepatosplenomegaly. Due to high suspicion, molecular genetic testing for LPL deficiency was sent and came back positive. DISCUSSION: Patients with LPL are classically found to have high serum plasma triglycerides, low HDL-cholesterol, and presence of fasting chylomicrons in the plasma due to mutation of the enzyme that is responsible for hydrolysis and removal of triglycerides from the plasma. The most feared complication of the disease is recurrent and potentially life threatening acute pancreatitis. Although this is a very rare condition, it is an important differential diagnosis to consider due to refractoriness of conventional medical therapies including statins, fibrates and reduced fat intake(less than 20 g/day). There have been some studies that suggested high dose antioxidant therapy could potentially help lower the level of triglycerides and prevent recurrent episodes of acute pancreatitis in that particular group of patients. It is also critical to make the diagnosis as soon as possible for early medical interventions during childhood and genetic counseling and testing for family members.

Utilization of High-Intensity Statins in Patients at Risk for Cardiovascular Events: A National Cross-Sectional Study.

The 2013 American College of Cardiology/American Heart Association cholesterol guidelines, which identified four groups of patients at risk for atherosclerotic cardiovascular disease events, departed from the target-based approach to managing cholesterol. The impact of these guidelines on high-intensity statin use across the United States is unclear. The primary objective was to evaluate the rate of high-intensity potential (HIP) statin use before and after the 2013 guidelines. The secondary objective was to identify predictors of HIP statin use within the study population. A national cross-sectional study was conducted using data from the National Ambulatory Medical Care Survey. Office visits involving patients aged 21-75 years where criteria for HIP statin therapy were met were included. Visits involving pregnant patients were excluded. Prescribing trends of HIP statins were measured from National Ambulatory Medical Care Survey data before and after the 2013 guidelines. Multivariate logistic regression identified variables associated with prescribing HIP statins. A total of 48,884 visits were included, representing more than 940 million office visits nationally. HIP statins were listed in 9.5% and 16.5% of visits before and after 2013, respectively (odds ratio [OR] 1.88; 95% confidence interval [CI] 1.62-2.20). The strongest predictors of HIP statin use were antihypertensive use (OR 5.38, 95% CI 4.67-6.20), comorbid hyperlipidemia (OR 2.93, 95% CI 2.62-3.29), Black race (OR 0.63, 95% CI 0.49-0.81), and Hispanic ethnicity (OR 0.65, 95% CI 0.52-0.80). Prescribing rates for HIP statins increased after the release of the 2013 guidelines. The prescribing rates were lower than expected, especially in Black and Hispanic patients. These observations signify opportunities to improve the quality of care for patients who are at risk for atherosclerotic cardiovascular disease events in the United States.

Evaluation of Aspirin and Statin Therapy Use and Adherence in Patients With Premature Atherosclerotic Cardiovascular Disease

Studies on the use of and adherence to secondary prevention therapies in patients with premature and extremely premature atherosclerotic cardiovascular disease (ASCVD) are lacking. To evaluate and compare aspirin use, any statin use, high-intensity statin use, and statin adherence among patients with premature or extremely premature ASCVD compared with patients with nonpremature ASCVD. This multicenter cross-sectional study used the clinical and administrative data sets of the US Department of Veterans Affairs (VA) to identify adult patients with at least 1 primary care visit in the VA health care system between October 1, 2014, and September 30, 2015. The study cohort comprised patients with ASCVD (ischemic heart disease, peripheral arterial disease, or ischemic cerebrovascular disease) who were enrolled in the Veterans With Premature Atherosclerosis (VITAL) registry. Patients with missing data for date of birth or sex and those with limited life expectancy were excluded. Data were analyzed from November 1, 2019, to January 1, 2020. Premature (the first ASCVD event occurred at age <55 years for men and age <65 years for women) vs nonpremature (the first ASCVD event occurred at age ≥55 years for men or age ≥65 years for women) ASCVD and extremely premature (the first ASCVD event occurred at age <40 years) vs nonpremature ASCVD. The primary outcomes were aspirin use, any statin use, high-intensity statin use, and statin adherence (measured by proportion of days covered [PDC] ≥0.8). Of the 1 248 158 patients identified, 135 703 (10.9%) had premature ASCVD (mean [SD] age, 49.6 [5.8] years; 116 739 men [86.0%]), 1 112 455 (89.1%) had nonpremature ASCVD (mean [SD] age, 69.6 [8.9] years; 1 104 318 men [99.3%]), and 7716 (0.6%) had extremely premature ASCVD (mean [SD] age, 34.2 [4.3] years; 6576 men [85.2%]). Patients with premature ASCVD vs those with nonpremature ASCVD had lower rates of aspirin use (96 468 [71.1%] vs 860 726 [77.4%]; P < .001) and any statin use (98 908 [72.9%] vs 894 931 [80.5%]; P < .001); had a statin PDC of 0.8 or higher (57 306 [57.9%] vs 644 357 [72.0%]; P < .001); and a higher rate of high-intensity statin use (49 354 [36.4%] vs 332 820 [29.9%]; P < .001). Similarly, patients with extremely premature ASCVD were less likely to use aspirin (odds ratio [OR], 0.27; 95% CI, 0.26-0.29), any statin (OR, 0.25; 95% CI, 0.24-0.27), or high-intensity statin (OR, 0.78; 95% CI, 0.74-0.82) and to be statin adherent (OR, 0.44; 95% CI, 0.41-0.47). In this study, patients with premature or extremely premature ASCVD appeared to be less likely to use aspirin or statins and to adhere to statin therapy. This finding warrants further investigation into premature ASCVD and initiatives, including clinician and patient education, to better understand and mitigate the disparities in medication use and adherence.

Prevalence and Characteristics of Patients With Primary Severe Hypercholesterolemia in a Multidisciplinary Healthcare System

Severe hypercholesterolemia (SH) includes individuals with LDL-C ≥ 190 mg/dl, regardless of cause. These individuals have a fivefold increased long-term risk for coronary artery disease. Although systematic SH screening can trigger early treatment, current treatment guidelines may not be fully implemented or followed by patients. To further understand this treatment gap, we used electronic health record data to retrospectively assess SH prevalence, characteristics, and treatment in a midwest US healthcare system, between 2009 and 2020. Comorbidities, tobacco exposure, and prescribed lipid-lowering therapies were assessed. Statistical analyses were conducted to identify differences between individuals with primary SH (LDL-C ≥ 190 mg/dl, group 1) and those without primary SH (LDL-C < 190 mg/dl, group 2). Of 265,220 records analyzed, 7.4% met the definition for primary SH. These group 1 cases had more comorbidities than group 2 cases, including premature coronary artery disease (5.8% vs 2.7%). Results showed most individuals in group 1 were treated by primary care providers (43.2% to 45.7%), than by specialty providers (2.5% to 3.3%), and these primary care providers prescribed mainly moderate-intensity statins. Seventy-seven percent of group 1 individuals were treated with a statin, 27% were treated with a high-intensity statin, and 4% were treated with ezetimibe. Fewer young patients (< 40 years) were treated with statins (50% to 58.3%) than older patients (74.0% to 76.3%). Although use of general statins, high-intensity statins, and ezetimibe was higher in individuals with SH than those without SH, treatment remains below guideline recommendations, especially in younger individuals.

Tendencias en el uso de estatinas tras un ictus isquémico. ¿Hemos cambiado nuestra práctica clínica?

IntroductionThe role of statins after ischaemic stroke changed with the publication of the SPARCL study in 2006. We analyse how this has influenced the prescription of statins in this patient population. MethodsWe conducted a retrospective study of patients discharged with ischaemic stroke at the Virgen Macarena, Virgen del Rocío, and Valme hospitals in Seville (Spain) over two periods: 1999-2001 and 2014-2016. ResultsThe study included 1575 patients: 661 (42%) were women and mean age (standard deviation) was 69 (10) years. Patients from the later period are older (68 [10] vs 71 [11]; P=.0001); include a higher proportion of women; and present higher rates of dyslipidaemia, hypertension, and diabetes. At discharge, statins were used in 18.7% of patients (vs 86.9% in the first period; P=.0001), with high-intensity statins prescribed in 11.1% of cases (vs 54.4%; P=.0001). In both periods, atorvastatin was the most commonly prescribed statin (80mg: 6% vs 42.7%; 40mg: 5.1% vs 11.1%). In the first period, the use of statins and high-intensity statins was correlated with hypercholesterolaemia, and inversely correlated with age. In the second period, statin use was correlated with hypertension and hypercholesterolaemia, and high-intensity statin use was correlated with ischaemic heart disease and inversely correlated with age. ConclusionThere has been a clear change in the prescription of statins to patients with ischaemic stroke at discharge. However, many patients remain undertreated and the use of these drugs needs to be optimised.

A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies.

IntroductionClinicians, payers, guideline committees, and policymakers support the use of high-intensity statins in patients at high risk for complications of cardiovascular disease (CVD). Guidelines and recommendations provide guidance on next steps for patients with inadequate low-density lipoprotein cholesterol (LDL-C) control on maximally tolerated statin or for those who are statin-intolerant. Ezetimibe and evolocumab improve CV outcomes when added to statins in high-CV-risk populations. The aim of the study was to compare evolocumab and ezetimibe for lipid-lowering efficacy and safety.MethodsWe summarized data from 1427 patients from three phase 3 evolocumab studies comparing double-blinded evolocumab vs. ezetimibe. These studies evaluated four distinct populations: those free of CVD receiving each agent as monotherapy, patients with CVD receiving add-on therapy to low- or high-intensity statin, and statin-intolerant patients. Lipid efficacy and safety were reported at week 12.ResultsAcross the studies, evolocumab reduced LDL-C by a mean 55–61% from baseline to week 12; ezetimibe lowered LDL-C by 18–20% from baseline (mean difference = 38–43% favoring evolocumab; p < 0.0001). This corresponded to absolute reductions in LDL-C of 60–104 mg/dL with evolocumab vs. 17–35 mg/dL with ezetimibe. Evolocumab also significantly improved other lipids and led to a higher percentage of patients achieving LDL-C goals vs. ezetimibe. Adverse events and discontinuation rates (oral and parenteral therapy) were balanced across groups, suggesting good tolerance and acceptance of both treatments.ConclusionsEvolocumab outperformed ezetimibe in efficacy and lipid goal attainment. Both products demonstrated good safety/tolerability. These data may help guide access decisions for high-risk patients with inadequate treatment response or intolerance to statin therapy.

TO001EFFECTS OF THE BET-INHIBITOR APABETALONE ON CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND ACUTE CORONARY SYNDROME, ACCORDING TO PRESENCE OR ABSENCE OF CHRONIC KIDNEY DISEASE. A BETONMACE TRIAL REPORT

Abstract Background and Aims Patients with type 2 diabetes (T2D) and acute coronary syndrome (ACS) are at high risk for recurrent cardiovascular (CV) events, particularly in the presence of chronic kidney disease (CKD). Apabetalone (APB) is a novel inhibitor of bromodomain and extraterminal (BET) proteins. Its cardiovascular efficacy and safety were evaluated in a phase 3 trial, BETonMACE. Method BETonMACE was a randomized, double-blind, comparison of effects of ABP or placebo (PBO) on major adverse CV events (MACE) defined as CV-death, non-fatal myocardial infarct or stroke, in 2425 pts with T2D and recent ACS. Here we report MACE plus CHF hospitalization in subjects with or without CKD Stage 3. Results Baseline characteristics: median age 62 years, 25.6% female, 87.6% white, 90% high intensity statin use, mean LDL-C 70.3 and HDL-C 33.3 mg/dl, median HbA1c 7.3%, and 11% with CKD Stage 3. Overall in the trial, MACE plus CHF hospitalization occurred in 139 (11.5%) patients with ABP and 173 (14.3%) with PBO (HR 0.78, 95% CI 0.63-0.98). In the subgroup with CKD, MACE plus CHF hospitalization occurred in 16 (12.9%) on APB and 41 (25%) on PBO (HR 0.48, 95% CI 0.26-0.89). In the subgroup without CKD, MACE plus CHF hospitalization occurred in 123 (11.3%) and 132 (12.7%) with APB or PBO, respectively (HR 0.89, 95% CI 0.70-1. Conclusion Patients with T2D, ACS, and Stage 3 CKD have a very high risk of subsequent MACE plus CHF hospitalization. The BET protein inhibitor ABP may reduce this risk.

1429-P: Use of Guideline-Recommended Risk-Reduction Strategies among Patients with Type 2 Diabetes and Established ASCVD: A 1-Year Update from Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD)

Due to emerging evidence, recent practice guidelines are emphasizing more aggressive use of effective prevention strategies in high-risk patients with diabetes (DM). We assessed changes in the use of evidence-based therapies among pts with DM from a registry of 5006 U.S. participants (pts) with ASCVD and LDL-C ≥70mg/dL across 120 U.S. centers taking lipid-lowering therapy (LLT). Among 1,622 DM pts with 12-month follow-up, 14% had intensification of LLT since baseline, 7% de-escalated. Median LDL-C at 12 months was 81 mg/dL, an 11% decrease from baseline. Among pts in the LDL-C cohorts, the percentage with LDL-C &amp;lt;70mg/dL increased from baseline through 12 months (Table). Use of statins and high-intensity statins was stable, while ezetimibe increased, and PCSK9i’s were initiated in 3% of pts not on a PCSK9i at enrollment. Use of SGLT2i, GLP-1RA’s, and fish oil did not change. At 12 months, 8% were on all guideline-recommended therapies for optimal risk reduction, similar to 7% at baseline (p for trend=0.1). Although some modest improvements in the use of secondary cardiovascular prevention therapies were observed, the proportion of patients with DM and ASCVD that receive optimal guideline-recommended risk reduction strategies remains very low. Disclosure M.N. Kosiborod: Consultant; Self; Amarin Corporation, Amgen, Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi US, Vifor Pharma Group. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. S.V. Arnold: None. J. Delemos: Consultant; Self; Amgen, Novo Nordisk A/S, Regeneron Pharmaceuticals. R.S. Rosenson: Advisory Panel; Self; Amgen, Medicines Company. Consultant; Self; CVS Caremark. Research Support; Self; Amgen, Medicines Company, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals. Other Relationship; Self; Amgen, Kowa Pharmaceuticals America, Inc., UpToDate. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen, Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Corvidia, Denka-Seiken Co., Ltd., Esperion Therapeutics, Inc., Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Matinas BioPharma, Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amgen, Esperion Therapeutics, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA. Y. Liu: None. K.E. Mues: Employee; Self; Amgen. Stock/Shareholder; Self; Amgen. S. Alam: Employee; Self; Amgen. D.L. Bhatt: Research Support; Self; Abbott, Afimmune, Amarin Corporation, Amgen, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Cardax, Chiesi USA, Inc., CSL Behring, Ferring Pharmaceuticals, Fractyl Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Ischemix, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis, Synaptic. C. Cannon: None. Funding Amgen Inc.

Association of Dry Eye Disease With Dyslipidemia and Statin Use

To determine whether an association exists between dry eye disease (DED) and statin use and/or dyslipidemia. Retrospective, case-control study. Setting: University of North Carolina (UNC)-affiliated healthcare facilities. 72,931 patients seen at UNC ophthalmology clinics over a 10-year period. Odds ratios (ORs) calculated between DED and a history of low, moderate, or high-intensity statin use; and ORs calculated between DED and abnormal lipid panel values. Total of 39,336 individuals (53.9% female) were analyzed after exclusion of individuals with confounding risk factors for DED. Of these, 3,399 patients (8.6%) carried a diagnosis of DED. Low-, moderate-, and high-intensity statin regimens were used by 751 subjects (1.9%), 2,655 subjects (6.8%), and 1,036 subjects (2.6%). Lipid abnormalities were identified as total cholesterol >200mg/dL, 4,558 subjects (11.6%); high-density lipoprotein (HDL) <40mg/dL, 2,078 subjects (5.3%); low-density lipoprotein (LDL) >130mg/dL, 2,756 subjects (7.0%); and triglycerides (TGs) >150mg/dL, 2,881 subjects (7.3%). The odds ratios (OR) of carrying a diagnosis of DED given the presence of low-, moderate-, and high-intensity statin use were 1.39 (95% confidence interval [CI]: 1.13-1.72); OR 1.47 (95% CI: 1.30-1.65), and OR 1.46 (95% CI: 1.21-1.75), respectively. The OR of carrying a diagnosis of DED given the presence of total cholesterol >200mg/dL, HDL <40mg/dL, LDL >130mg/dL, and TGs >150mg/dL were 1.66 (95% CI: 1.52-1.82), 1.45 (95% CI: 1.26-1.67), 1.55 (95% CI: 1.39-1.74), and 1.43 (95% CI: 1.27-1.61), respectively. A history of statin use or dyslipidemia is associated with an increased odds of having a DED diagnosis. Further studies are needed to determine whether statin use and/or dyslipidemia increases the risk of DED.

Long-Term Benefit and Withdrawal Effect of Statins After Percutaneous Coronary Intervention: A Nationwide Population-Based Cohort Study.

PurposeDespite indubitable evidence for the cardiovascular benefits of statins, there have been concerns that statin discontinuation may cause negative effects known as “statin withdrawal syndrome.” This study aimed to assess the benefit and the withdrawal effect of statins after percutaneous coronary intervention (PCI).Patients and MethodsWe conducted a retrospective cohort study on 5218 patients who underwent PCI between 2002 and 2013 using the nationwide health insurance claim data in Korea. Based on the prescription data, the use of statins during follow-up was classified into three risk periods: “statin period” (period with statin cover), “statin withdrawal period” (withdrawal of statin within 30 days), and “no statin period” (no exposure to statin for longer than 30 days). The primary outcome was the composite outcome of myocardial infarction, coronary revascularization, stroke, and all-cause death. We performed multivariate Cox proportional regression analyses which treated the use of statins as a time-dependent variable.ResultsDuring the follow-up period of 3.54 ± 2.91 years (mean ± standard deviation), 1515 (29.0%) patients sustained a primary outcome. Compared with the “no statin period,” the “statin period” was associated with lower risk of the primary outcome (adjusted hazard ratio [HR] 0.72, 95% confidence interval [CI, 0.63–0.81]). While the “statin withdrawal period” posed a significantly increased risk (adjusted HR 1.87, 95% CI [1.52–2.29]). With respect to the intensity of statins associated with withdrawal, dose-dependent increased risk was observed for withdrawal of low-, moderate-, and high-intensity statins; adjusted HR [95% CI] were 1.45 [0.74–2.86], 1.86 [1.49–2.32], and 2.61 [1.41–4.81], respectively.ConclusionAfter PCI, there was an increased cardiovascular risk during the statin withdrawal period, especially with the use of high-intensity statins. To maximize the beneficial effect and to avoid the withdrawal effect of statins, high-risk patients need to adhere to taking statins without discontinuation.

CHALLENGES IN CHOLESTEROL MANAGEMENT IN PATIENTS WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASE: INSIGHTS FROM PATIENT AND PHYSICIAN SURVEYS IN THE GOULD STUDY

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

STATIN USE FOR SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE IN THE ELDERLY

The AHA/ACC secondary prevention guidelines recommend moderate or high intensity statin use in patients >75 years of age. We sought to understand statin prescribing patterns and clinical outcomes in this population. We analyzed electronic health record data of adults >75 years old with ASCVD from a

STATIN TREATMENT PATTERNS AMONG PATIENTS WITH ACUTE MYOCARDIAL INFARCTION IN AN INTEGRATED HEALTHCARE SYSTEM

Lipid lowering therapy, particularly use of high-intensity statins (HIS) is vital for secondary prevention of cardiovascular events, after acute myocardial infarction (AMI). However, physician prescription patterns for HIS are not well documented in the real-world setting in post-AMI patients. We