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This article emphasizes the pivotal role of economic evaluation in the management of cardiovascular diseases (CVDs) within the Indian healthcare system. It explores the importance of economic evaluation methodologies such as cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis in guiding informed healthcare decisions related to CVD management. Additionally, it discusses the unique challenges and opportunities surrounding health technology assessment (HTA) and economic evaluation specific to India, providing insights into potential areas for improvement. By giving precedence to economic evaluation, India can optimize the allocation of resources, improve patient outcomes, and alleviate the economic burden associated with CVDs. The implementation of these recommendations has the potential to significantly enhance the efficiency and effectiveness of CVD management strategies in India, ultimately leading to improved healthcare outcomes for the population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Author currently working with biopharma comany If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Lipoprotein(a) [Lp(a)] is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether the optimal Lp(a) threshold for risk assessment should differ based on baseline ASCVD status is unknown., Objectives: The purpose of this study was to assess the association between Lp(a) and major adverse cardiovascular events (MACE) among patients with and without baseline ASCVD., Methods: We studied a retrospective cohort of patients with Lp(a) measured at 2 medical centers in Boston, Massachusetts, from 2000 to 2019. To assess the association of Lp(a) with incident MACE (nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or cardiovascular mortality), Lp(a) percentile groups were generated with the reference group set at the first to 50th Lp(a) percentiles. Cox proportional hazards modeling was used to assess the association of Lp(a) percentile group with MACE., Results: Overall, 16,419 individuals were analyzed with a median follow-up of 11.9 years. Among the 10,181 (62%) patients with baseline ASCVD, individuals in the 71st to 90th percentile group had a 21% increased hazard of MACE (adjusted HR: 1.21; P < 0.001), which was similar to that of individuals in the 91st to 100th group (adjusted HR: 1.26; P < 0.001). Among the 6,238 individuals without established ASCVD, there was a continuously higher hazard of MACE with increasing Lp(a), and individuals in the 91st to 100th Lp(a) percentile group had the highest relative risk with an adjusted HR of 1.93 (P < 0.001)., Conclusions: In a large, contemporary U.S. cohort, elevated Lp(a) is independently associated with long-term MACE among individuals with and without baseline ASCVD. Our results suggest that the threshold for risk assessment may be different in primary vs secondary prevention cohorts., Competing Interests: Funding Support and Author Disclosures This study was funded, in part, by Amgen Inc. Dr Januzzi is a Trustee of the American College of Cardiology; has received grant support from Abbott, Applied Therapeutics, HeartFlow Inc, Innolife, and Roche Diagnostics; has received consulting income from Abbott, AstraZeneca, Bayer, Beckman, Boehringer Ingelheim, Janssen, Novartis, Merck, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Intercept, Pfizer, and Takeda. Drs Booth III, López, and Kent are employees and shareholders of Amgen Inc. Dr Bhatt has served on the Advisory Board of Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; has served on the Board of Directors of American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); has served as a consultant for Broadview Ventures, Hims, SFJ, and Youngene; has served on Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo; for the ABILITY-DM trial, funded by Concept Medical; and for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health-funded MINT Trial); has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); served as Deputy Editor of Clinical Cardiology; is named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon (neither he nor Brigham and Women's Hospital receive any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); has served as site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; is a Trustee of the American College of Cardiology; and has performed unfunded research for FlowCo. Dr Blankstein has received research support and consulting fees from Amgen Inc and Novartis Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Low-density lipoprotein cholesterol (LDL-C) is among the most important modifiable risk factors for cardiovascular disease. In very high-risk patients, the European Society of Cardiology/European Atherosclerosis Society guidelines recommend attaining LDL-C < 55 mg/dL. In the German cohort of the observational HEYMANS study, we aimed to describe the clinical characteristics and LDL-C control among patients initiating evolocumab., Methods: Data was collected between 09/2016 and 05/2021 for ≤ 6 months before (retrospectively) and ≤ 30 months after evolocumab initiation (prospectively). Patient characteristics, lipid-lowering therapy (LLT), lipid values, evolocumab use, and safety were collected., Results: Of 380 enrolled patients, 93% received evolocumab in secondary prevention and 69% had a history of statin intolerance. At study baseline, 49% did not receive any statins and LDL-C was very high (145 mg/dL). Use of evolocumab decreased LDL-C by a median of 53% within 3 months and remained stable thereafter, despite mainly unchanged background LLT. Overall, 59% attained an LDL-C level < 55 mg/dL (69% with, 49% without LLT). Persistence to evolocumab was 90.6% in months 1-12 and 93.5% in months 13-30. Adverse drug reactions were reported in 8% of patients., Conclusion: Data from the German HEYMANS cohort corroborate previous reports on evolocumab effectiveness and safety in clinical practice. Evolocumab initiation was associated with a rapid and sustained LDL-C reduction. Persistence with evolocumab was high. Our finding that patients receiving an evolocumab/LLT combination are more likely to attain the LDL-C goal than those receiving evolocumab alone corroborates previous data showing the importance of using highly intensive therapy. Graphical abstract available for this article., Trial Registration: ClinicalTrials.gov Identifier NCT02770131 (registration date 27 April 2016)., (© 2024. The Author(s).)

Background: The reduction of low-density lipoprotein cholesterol (LDL-C) with evolocumab, a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9i), reduces the risk of major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD) with a prior MI, prior stroke, or symptomatic peripheral artery disease, with no offsetting safety concerns. The effect of evolocumab on CV outcomes in lower risk patients without a history of MI or stroke has not been explored., Study Design: VESALIUS-CV is a randomized, double-blind, placebo-controlled, global clinical trial designed to evaluate the effect of evolocumab on the risk of major cardiovascular events in patients at high cardiovascular risk but without a prior ischemic event. The study population consists of 12,301 patients with atherosclerosis or high-risk diabetes mellitus without a prior MI or stroke; an LDL-C ≥ 90 mg/dL, or non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 120 mg/dL, or apolipoprotein B ≥ 80 mg/dL; and treated with optimized lipid-lowering therapy. Patients were randomized in a 1:1 ratio to evolocumab 140 mg subcutaneously every 2 weeks or matching placebo. The primary efficacy objective is to assess whether evolocumab reduces the risk of the dual primary composite endpoints of coronary heart disease (CHD) death, myocardial infarction (MI), or ischemic stroke (triple primary endpoint) and of CHD death, MI, ischemic stroke, or ischemia-driven arterial revascularization (quadruple primary endpoint). Recruitment began in June 2019 and completed in November 2021. The trial is planned to continue until at least 751 patients experience an adjudicated triple endpoint, at least 1254 experience an adjudicated quadruple endpoint, and the median follow-up is ≥4.5 years., Conclusion: VESALIUS-CV will determine whether the addition of evolocumab to optimized lipid-lowering therapy reduces cardiovascular events in patients at high cardiovascular risk without a prior MI or stroke., Trial Registration: NCT03872401., Competing Interests: Disclosures Drs. Bohula, Giugliano, Marston, Murphy and Sabatine are members of the TIMI Study Group. The TIMI Study Group reports grant support through Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc., Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Siemens Healthcare Diagnostics, Inc., Softcell Medical Limited, Verve Therapeutics, Zora Biosciences. Dr. Bohula reports personal fees from Kowa, Novo Nordisk, Servier and Esperion. Dr. Marston reports no personal fees. Dr. Leiter reports personal fees from Amarin, Amgen, AstraZeneca, HLS, Kowa, Merck, Pfizer, and Sanofi. Dr. Bhatia, Dr. Wang and Ms. Elliott-Davey are employees and stockholders of Amgen. Dr. Ruzza is former Amgen employee and stockholder, has a pending patent application PCT/US2021/034489 on PCSK9 inhibitors and methods of use thereof to treat cholesterol-related disorders, and is currently GSK employee and stockholder. Dr. Giugliano reports personal fees from Amgen, Daiichi-Sankyo, Dr. Reddy's Laboratories, Inventiva Pharma, Medical Education Resources, Pfizer, Sanofi, SUMMEET. Dr. Sabatine reports personal fees from Amgen; Anthos Therapeutics; AstraZeneca; Beren Therapeutics; Boehringer Ingelheim; Dr. Reddy's Laboratories; Fibrogen; Intarcia; Merck; Moderna; Novo Nordisk; Precision BioSciences; Silence Therapeutics., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cardiovascular disease (CVD) is one of the leading causes of death in Belgium. Current strategies for the prevention and management of CVD focus on reducing low-density lipoprotein cholesterol (LDL-C) levels. This analysis assessed whether LDL-C goals, recommended by the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines, were being achieved in a Belgian study population., Methods: The cross-sectional, observational, DA VINCI study enrolled patients prescribed lipid-lowering therapy (LLT) between 21 June 2017 and 20 November 2018. Data for patients from Belgium were extracted for this country-specific analysis. Primary endpoint was the proportion of patients who achieved 2016 ESC/EAS risk-based LDL-C goals; attainment of 2019 risk-based LDL-C goals was evaluated post hoc ., Results: Of 497 enrolled patients, 41% were female and mean age was 68 years. Among subjects with an LDL-C measurement on stabilised LLT, moderate-intensity statin monotherapy was the most prescribed LLT regimen (59%). Overall, 63% of patients achieved their risk-based LDL-C goals according to the 2016 ESC/EAS guidelines. Among patients with established ASCVD, risk-based LDL-C goal attainment was higher in patients with peripheral arterial disease (53%) than patients with coronary (37%) and cerebrovascular disease (42%). According to the updated 2019 ESC/EAS guidelines, less than half (41%) of patients achieved their risk-based LDL-C goal. The proportion of primary and secondary prevention patients who achieved 2019 risk-based LDL-C goals was 59% and 18%, respectively., Conclusion: These findings reveal a large gap between the LDL-C goals advocated by the ESC/EAS and the levels achieved in routine clinical practice in Belgium.

Aim: The PERI-DYS study aims to characterize two groups of patients with dyslipidaemia at very high CV risk: PCSK9i receivers and patients qualifying for but not receiving PCSK9i., Methods: This is an observational study by office-based and clinic-based physicians, mainly cardiologists and other internists in Germany, with data extracted from patient charts., Clinicaltrials: gov identifier NCT03110432., Results: A total of 1659 patients were enrolled across 70 sites. The majority of patients (91.0%) were reported as having mixed dyslipidaemia or non-familial or heterozygous familial hypercholesterolemia. At enrolment, 794 (47.9%) of patients were PCSK9i receivers (of these 65.9% ongoing, and 34.1% newly treated within 30 days before their baseline visit). Among PCSK9i receivers, the majority had evolocumab 140 mg (n = 632, 38.1% of total). PCSK9i receivers compared to non-receivers were about 2 years younger and had a lower proportion of males. In terms of comorbidities, they had (statistically significantly) more often CAD, and less often PAD, diabetes mellitus, arterial hypertension and chronic renal disease. The calculated untreated median LDL-C was 187 mg/dl (IQR 127; 270) in ongoing PCSK9i receivers, 212 mg/dl (IQR 132; 277) in newly treated PCSK9i receivers, and 179 mg/dl (IQR 129; 257) in non-receivers. Physician-reported statin intolerance was much more common in the two PCSK9i receiver groups as compared to non-receivers (67.3% versus 15.3%). Consequently, patients in the PCSK9i groups received fewer concomitant statins. Mean total cholesterol (143 vs. 172 mg/dl) and LDL-C (69 vs. 99 mg/dl) were considerably lower in ongoing PCSK9i receivers compared to non-receivers., Conclusions: PCSK9i receivers are characterized by higher baseline LDL-C and a higher portion of statin intolerance compared to those qualified for but not-receiving PCSK9i treatment. On-treatment, LDL-C was lower in PCSK9i receivers. Ongoing follow-up will determine the prognostic importance of these findings., (© 2022. The Author(s).)

Background and Objectives: This study quantified the 'distance to LDL-C goal' in patients at very high cardiovascular risk with uncontrolled hyperlipidaemia. 'Distance to LDL-C goal' was defined as the percentage by which low-density lipoprotein cholesterol (LDL-C) levels needed to be reduced to achieve the LDL-C goals specified in the 2016 or 2019 European Society of Cardiology/European Atherosclerosis Society guidelines., Design and Methods: This retrospective analysis using data from the IQVIA Disease Analyzer database included patients who were predominantly treated by a primary care physician, diabetologist or cardiologist between 2014 and 2018, with a diagnosis of hyperlipidaemia and an initial LDL-C measurement (index event) and one or more cardiovascular risk factors. The primary outcome was to assess the proportion of patients with uncontrolled hyperlipidaemia and to classify the 'distance to LDL-C goal' in these patients., Results: Data from 32,963 patients were analysed ( n  = 27,159, n  = 3873 and n  = 1931 patients in the primary care physician, diabetology and cardiology cohorts, respectively). Most patients had uncontrolled LDL-C levels (⩾70 mg/dL; ⩾1.8 mmol/L) at index (91.0%, 86.4% and 94.0% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). Analysis of the 'distance to LDL-C goal' indicated that approximately one-third of patients in each cohort required an LDL-C level reduction of up to 50% relative to index to achieve their LDL-C goal (35.8%, 43.7% and 28.4% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). LDL-C control was not achieved at 36 months post-index in most patients with uncontrolled LDL-C levels (86.8%, 81.7% and 90.2% of patients in the primary care physician, diabetology and cardiology cohorts, respectively)., Conclusion: LDL-C levels were uncontrolled in most patients with hyperlipidaemia. Analysis of the 'distance to LDL-C goal' showed that most patients required a substantial LDL-C level reduction to achieve their LDL-C goal.

Introduction: The 2018 American Heart Association (AHA)/American College of Cardiology (ACC)/Multisociety blood cholesterol guidelines recommend clinicians consider adding non-statin therapy for patients with very high-risk (VHR) atherosclerotic cardiovascular disease (ASCVD) and low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dl while receiving maximally tolerated statins. However, according to a recent study, only 17.1% of patients with established ASCVD received appropriate lipid-lowering therapy (LLT) intensification. Here, we describe the design of a prospective, 12-month study (LOGAN-CV) evaluating a multifaceted site-level intervention to enhance clinicians' adherence to guidelines to improve LDL-C levels for patients with VHR ASCVD., Methods: Clinicians from up to ten research sites are eligible if they care for adult patients with ASCVD. Interventions include educational modules, a cloud-based performance platform providing clinicians a tailored summary of their LDL-C management performance, newsletters, periodic peer-to-peer calls, and pre- and post-intervention surveys evaluating knowledge, attitudes, and beliefs around LDL-C management, with additional interventions for clinicians demonstrating a lower readiness to make treatment decisions based on guideline recommendations. Patients with VHR ASCVD, defined as having recent myocardial infarction and LDL-C ≥ 70 mg/dl despite statin treatment, will be included in the study. Patient data will be collected from electronic medical records from baseline (clinician enrollment) through the 12-month intervention. The study started in October 2022, with anticipated completion in March 2024., Planned Outcomes: The change in proportion of patients with LDL-C < 70 mg/dl achieved at any time during the 12-month intervention (primary); LLT intensification, changes in guideline-aligned LDL-C testing and LLT titration over 12 months, and change in overall clinicians' knowledge, attitudes, and beliefs are key outcomes of interest. The LOGAN-CV study addresses a critical unmet need in LDL-C control in patients with VHR ASCVD and evaluates the effect of a multifaceted intervention targeting clinicians to improve their adherence to guidelines and consequently improve clinical outcomes for patients., (© 2023. The Author(s).)

Background: Cardiovascular disease (CVD) represents the primary cause of death and disability globally, with elevated cholesterol as one of the leading risk factors for CVD. We describe the clinical characteristics, treatment patterns, and effectiveness of evolocumab in treating hyperlipidemia., Methods: Observational study conducted through a chart review of patients with hyperlipidemia receiving evolocumab as part of clinical management in Colombia., Results: This study included 115 patients treated with evolocumab. A total of 101 patients (87.8%) had a history of CVD, 13 (11.3%) familial hypercholesterolemia (FH), and 23 (20%) type 2 diabetes. Thirty-nine patients reported intolerance to any statin (33.9%). The median value of LDL-C before initiation of evolocumab was 147mg/dL (IQR: 122.5-183.7mg/dL). Within the first 3 months of treatment, LDL-C value dropped to a median value of 53mg/dL (IQR: 34.0-95.5mg/dL), showing a reduction of 63.9%. The median LDL-C values remained below 45mg/dL until the end of follow-up. Among the patients with available data, up to 61% achieved an LDL-C level below 55mg/dL at the 10-12-month follow-up. A total of 72% of patients were persistent with treatment. Safety results showed a low frequency of hospitalizations (≤2%) and treatment-emergent adverse drug reactions (5.2%). No serious adverse events were reported., Conclusions: Evolocumab was associated with reductions in LDL-C levels, with a relative decrease of 63.9% within the first 3 months of treatment. Low rates of interruptions due to adverse events and adequate medication persistence was reported., (Copyright © 2023 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Cardiovascular diseases are considered the leading cause of death globally. This study describes the demographic characteristics, treatment patterns, self-reported compliance and persistence, and to explore variables related to non-adherence of patients enrolled in the cardiovascular patient support program (PSP) for evolocumab treatment in Colombia., Methods: This retrospective observational of the data registry of patients who entered the evolocumab PSP program., Results: The analysis included 930 patients enrolled in the PSP (2017-2021). Mean age was 65.1 (SD±13.1) and49.1% patients were female. The mean compliance rate to evolocumab treatment was 70.5% (SD±21.8). A total of 367 patients (40.5%) reported compliance higher than 80%. Persistence analysis included 739 patients (81.5%) where 87.8% of these patients were considered persistent to treatment. A total of 871 patients (93.7%) reported the occurrence of at least one adverse event during the follow-up period (mostly non-serious)., Conclusion: This is the first real-life study describing patient characteristics, compliance and continuity of treatment for dyslipidemia in a patient support program in Colombia. The overall adherence found was higher than 70%; similar to findings reported in other real-life studies with iPCSK9. However, the reasons for low compliance were different, highlighting the high number of administrative and medical reasons for suspension or abandonment of treatment with evolocumab., (Copyright © 2023. Publicado por Elsevier España, S.L.U.)

Purpose: To assess the cost-effectiveness of evolocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, compared with ezetimibe, both added to background statin therapy in patients with recent acute coronary syndrome (ACS) events (in the past 12 months) and low-density lipoprotein cholesterol (LDL-C) levels ≥ 100 mg/dL in China., Methods: A health economic evaluation was performed from a Chinese healthcare perspective, using a Markov model over a lifetime horizon based on a baseline cardiovascular (CV) event rate from claims database data and efficacy from the FOURIER trial. The health benefit was reflected in the decrease of LDL-C level, which led to a decrease of cardiovascular events. The costs of cardiovascular events and the utility value of each health state were derived from the published literature. Sensitivity analyses were conducted to evaluate the effects of uncertainty in parameters and the robustness of the model. The cost-effectiveness of evolocumab was also explored in patients with recent myocardial infarction (MI), at very high risk (VHR) of atherosclerotic cardiovascular disease (ASCVD), and homozygous familiar hypercholesterolemia (HoFH)., Results: In patients with recent ACS, evolocumab was associated with incremental quality-adjusted life-years (QALYs) of 1.33 and incremental costs of 115,782 yuan versus ezetimibe, both with background statin therapy, resulting in an incremental cost-effectiveness ratio (ICER) of 87,050 yuan per QALY gained. The probability of evolocumab + statins being cost-effective at a threshold of 217,341 yuan (three times per capita GDP, 2020), compared with ezetimibe + statins, was 100% in patients with recent ACS, recent MI, VHR ASCVD, and HoFH., Conclusion: Compared with ezetimibe + statins, the combination of evolocumab + statins was found to be cost-effective at a threshold of 217,341 yuan (three times per capita GDP, 2020) in patients with recent ACS events in China., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated., Methods: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated., Results: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively., Conclusion: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach., (© 2022. The Author(s).)

Importance: Whether protein risk scores derived from a single plasma sample could be useful for risk assessment for atherosclerotic cardiovascular disease (ASCVD), in conjunction with clinical risk factors and polygenic risk scores, is uncertain., Objective: To develop protein risk scores for ASCVD risk prediction and compare them to clinical risk factors and polygenic risk scores in primary and secondary event populations., Design, Setting, and Participants: The primary analysis was a retrospective study of primary events among 13 540 individuals in Iceland (aged 40-75 years) with proteomics data and no history of major ASCVD events at recruitment (study duration, August 23, 2000 until October 26, 2006; follow-up through 2018). We also analyzed a secondary event population from a randomized, double-blind lipid-lowering clinical trial (2013-2016), consisting of individuals with stable ASCVD receiving statin therapy and for whom proteomic data were available for 6791 individuals., Exposures: Protein risk scores (based on 4963 plasma protein levels and developed in a training set in the primary event population); polygenic risk scores for coronary artery disease and stroke; and clinical risk factors that included age, sex, statin use, hypertension treatment, type 2 diabetes, body mass index, and smoking status at the time of plasma sampling., Main Outcomes and Measures: Outcomes were composites of myocardial infarction, stroke, and coronary heart disease death or cardiovascular death. Performance was evaluated using Cox survival models and measures of discrimination and reclassification that accounted for the competing risk of non-ASCVD death., Results: In the primary event population test set (4018 individuals [59.0% women]; 465 events; median follow-up, 15.8 years), the protein risk score had a hazard ratio (HR) of 1.93 per SD (95% CI, 1.75 to 2.13). Addition of protein risk score and polygenic risk scores significantly increased the C index when added to a clinical risk factor model (C index change, 0.022 [95% CI, 0.007 to 0.038]). Addition of the protein risk score alone to a clinical risk factor model also led to a significantly increased C index (difference, 0.014 [95% CI, 0.002 to 0.028]). Among White individuals in the secondary event population (6307 participants; 432 events; median follow-up, 2.2 years), the protein risk score had an HR of 1.62 per SD (95% CI, 1.48 to 1.79) and significantly increased C index when added to a clinical risk factor model (C index change, 0.026 [95% CI, 0.011 to 0.042]). The protein risk score was significantly associated with major adverse cardiovascular events among individuals of African and Asian ancestries in the secondary event population., Conclusions and Relevance: A protein risk score was significantly associated with ASCVD events in primary and secondary event populations. When added to clinical risk factors, the protein risk score and polygenic risk score both provided statistically significant but modest improvement in discrimination.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development., (© 2023. The Author(s).)

Objectives: To describe the occurrence of recurrent atherosclerotic cardiovascular disease (ASCVD) events within 3 years after a new-onset event, the associated disease burden and statin prescribing in patients with ASCVD in Taiwan., Design: Retrospective cohort study., Setting: This was a retrospective cohort study using Taiwan's National Health Insurance Research Database., Participants: In total, 111 399, 133 538 and 21 572 patients who were hospitalised with diagnosis of coronary heart disease (CHD), cerebrovascular disease (CBVD) and peripheral artery disease (PAD), respectively, between 1 January 2012 and 31 December 2014., Primary and Secondary Outcome Measures: For each index and recurrent event, patients were observed for 12 months after admission to quantify risks of mortality, recurrent events, statin treatment and healthcare use., Results: We identified 97 321, 120 914 and 14 794 patients with new-onset CHD, CBVD and PAD, respectively. The proportions of developing first, second and third recurrent events were 22.5%, 25.6% and 30.9% for CHD; 20.9%, 26.2% and 32.4% for CBVD and 40.2%, 41.4% and 43.6% for PAD, respectively. Most patients had the same type of ASCVD for their recurrent events as their new-onset event. The mortality rates increased with each recurrent event (p<0.05 for all three ASCVD groups). The rates of hospital readmission and emergency room (ER) visit increased with increasing recurrent events. For example, in the CHD group, the 1-year readmission rates following the index, first and second recurrent events were 43.1%, 47.6% and 55.3%, respectively, and the proportions of visiting ER were 46.4%, 51.9% and 57.8%, respectively. Statin prescribing was suboptimal at time of index event and recurrent events., Conclusion: Recurrent ASCVD events were associated with a higher risk of recurrent event and mortality and greater healthcare use. However, statin prescriptions at index event and after each recurrent event were suboptimal., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: Wei-JC and Y-HY are employees of Amgen Taiwan Limited. C-YH, Wen-JC, H-JL, H-MC, C-MC and F-YH received a grant from Amgen Taiwan Limited., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To examine improvement in the use of optimal medical therapy (OMT) for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD) and diabetes., Materials and Methods: Patients with ASCVD (coronary, cerebrovascular, peripheral) and low-density lipoprotein-cholesterol of 70 mg/dl or higher were enrolled from December 2016 to July 2018 from 107 US sites/physicians (47% cardiology, 41% primary care, 12% other) and prospectively followed for 2 years (current analysis restricted to subgroup with diabetes). OMT was defined as high-intensity lipid-lowering (high-intensity statin, any statin + ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitor), antithrombotic (antiplatelet or anticoagulant), angiotensin-converting enzyme-inhibitor/angiotensin II receptor blocker/angiotensin receptor neprilysin inhibitor (ACE-I/ARB/ARNI) (excluding glomerular filtration rate [GFR] < 30 ml/min/1.73m 2 ) and sodium-glucose co-transporter-2 inhibitor (SGLT2i)/glucagon-like peptide-1 receptor agonist (GLP-1 RA) (excluding GFR < 30 ml/min/1.73m 2 and type 1 diabetes)., Results: Among 1590 patients with ASCVD and diabetes (96% type 2 diabetes), 58% were on high-intensity lipid-lowering therapy at the end of follow-up, 87% antithrombotic, 71% ACE-I/ARB/ARNI and 17% SGLT2i/GLP-1 RA. Overall, 11% of patients received comprehensive OMT, which modestly improved over time (vs. 8% at baseline; P = .002). Patients treated by cardiologists (vs. non-cardiologists) were more likely to be on high-intensity lipid lowering, but less likely to be on an SGLT2i/GLP-1 RA, and thus had lower rates of composite OMT (7.8% vs. 13.7%, P < .001). In a hierarchical multivariable model, older age was associated with lower odds of OMT (OR 0.74 per 10 years, 95% CI 0.60-0.90), whereas private insurance (OR 1.93, 95% CI 1.32-2.84) and coronary disease (OR 1.62, 95% CI 1.01-2.61) were associated with higher odds. The median odds ratio was 1.82 (95% CI 1.03-7.32), indicating a moderate variability in OMT use, independent of patient factors., Conclusions: We found suboptimal use of secondary prevention in US patients with ASCVD and diabetes, with minimal improvement over time. Further efforts are needed to improve the use of secondary prevention therapies in these patients with high residual risk., (© 2023 John Wiley & Sons Ltd.)

Background: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for atherosclerotic cardiovascular disease. However, the optimal achieved LDL-C level with regard to efficacy and safety in the long term remains unknown., Methods: In FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), 27 564 patients with stable atherosclerotic cardiovascular disease were randomized to evolocumab versus placebo, with a median follow-up of 2.2 years. In the open-label extension (FOURIER-OLE), 6635 of these patients were transitioned to open-label evolocumab regardless of initial treatment allocation in the parent trial and were followed for an additional median of 5 years. In this prespecified analysis, we examined the relationship between achieved LDL-C levels (an average of the first 2 LDL-C levels measured) in FOURIER-OLE (available in 6559 patients) and the incidence of subsequent cardiovascular and safety outcomes. We also performed sensitivity analyses evaluating cardiovascular and safety outcomes in the entire FOURIER and FOURIER-OLE patient population. Multivariable modeling was used to adjust for baseline factors associated with achieved LDL-C levels., Results: In FOURIER-OLE, 1604 (24%), 2627 (40%), 1031 (16%), 486 (7%), and 811 (12%) patients achieved LDL-C levels of <20, 20 to <40, 40 to <55, 55 to <70, and ≥70 mg/dL, respectively. There was a monotonic relationship between lower achieved LDL-C levels-down to very low levels <20 mg/dL-and a lower risk of the primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina or coronary revascularization) and the key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) that persisted after multivariable adjustment (adjusted P trend <0.0001 for each end points). No statistically significant associations existed in the primary analyses between lower achieved LDL-C levels and increased risk of the safety outcomes (serious adverse events, new or recurrent cancer, cataract-related adverse events, hemorrhagic stroke, new-onset diabetes, neurocognitive adverse events, muscle-related events, or noncardiovascular death). Similar findings were noted in the entire FOURIER and FOURIER-OLE cohort up to a maximum follow-up of 8.6 years., Conclusions: In patients with atherosclerotic cardiovascular disease, long-term achievement of lower LDL-C levels, down to <20 mg/dL (<0.5 mmol/L), was associated with a lower risk of cardiovascular outcomes with no significant safety concerns., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01764633.

Aim: There is a need to understand the management status of hypertension, dyslipidemia/hypercholesterolemia, and diabetes mellitus in the Asia-Pacific region (APAC). Methods: We conducted a systematic literature review and meta-analysis to summarize the awareness, treatment, and/or control rates of these risk factors in adults across 11 APAC countries/regions. Results: We included 138 studies. Individuals with dyslipidemia had the lowest pooled rates compared with those with other risk factors. Levels of awareness with diabetes mellitus, hypertension, and hypercholesterolemia were comparable. Individuals with hypercholesterolemia had a statistically lower pooled treatment rate but a higher pooled control rate than those with hypertension. Conclusion: The management of hypertension, dyslipidemia, and diabetes mellitus was suboptimal in these 11 countries/regions.

Background/purpose: Tumor necrosis factor inhibitors (TNFi) may have a direct benefit on cardiovascular (CV) disease beyond reducing rheumatoid arthritis (RA) disease activity measured by the Clinical Disease Activity Index (CDAI)., Methods: We compared TNFi initiators and methotrexate (MTX) monotherapy initiators from the CorEvitas RA registry. Two approaches to the "direct effect" of TNFi beyond CDAI were used. In the natural direct effect (NDE) analysis, the potential CV benefit of TNFi was partitioned into NDE and the natural indirect effect (NIE) mediated by CDAI during the first 6 months. We also estimated the controlled direct effects (CDE), corresponding to the direct benefit of TNFi when CDAI trajectories were hypothetically equalized between the initiators of TNFi and MTX monotherapy at a constant value. Estimates were given on the hazard ratio scale., Results: We identified 5764 initiators of TNFi and 3588 initiators of MTX monotherapy. TNFi initiators were younger (58 vs. 64 years) with a shorter disease duration. Our total effect estimates (TNFi vs. MTX [reference]) were protective in direction (0.76-0.91). The NDE estimate was 0.76 [95% confidence interval (CI) 0.59, 0.98], whereas the NIE estimate was 1.00 [95%CI 1.00, 1.00]. In the CDE analyses accounting for longitudinal CDAI, the CDE estimates was 1.27 [95%CI 0.60, 2.69]., Conclusions: We could not convincingly demonstrate a direct benefit of TNFi outside its impact on CDAI. At present, the emphasis should be on the stringent control of RA disease activity, a known important CV risk factor, regardless of medication choice., (© 2022 John Wiley & Sons Ltd.)

Aims: Syncope is a common and clinically challenging condition. In this study, the genetics of syncope were investigated to seek knowledge about its pathophysiology and prognostic implications., Methods and Results: This genome-wide association meta-analysis included 56 071 syncope cases and 890 790 controls from deCODE genetics (Iceland), UK Biobank (United Kingdom), and Copenhagen Hospital Biobank Cardiovascular Study/Danish Blood Donor Study (Denmark), with a follow-up assessment of variants in 22 412 cases and 286 003 controls from Intermountain (Utah, USA) and FinnGen (Finland). The study yielded 18 independent syncope variants, 17 of which were novel. One of the variants, p.Ser140Thr in PTPRN2, affected syncope only when maternally inherited. Another variant associated with a vasovagal reaction during blood donation and five others with heart rate and/or blood pressure regulation, with variable directions of effects. None of the 18 associations could be attributed to cardiovascular or other disorders. Annotation with regard to regulatory elements indicated that the syncope variants were preferentially located in neural-specific regulatory regions. Mendelian randomization analysis supported a causal effect of coronary artery disease on syncope. A polygenic score (PGS) for syncope captured genetic correlation with cardiovascular disorders, diabetes, depression, and shortened lifespan. However, a score based solely on the 18 syncope variants performed similarly to the PGS in detecting syncope risk but did not associate with other disorders., Conclusion: The results demonstrate that syncope has a distinct genetic architecture that implicates neural regulatory processes and a complex relationship with heart rate and blood pressure regulation. A shared genetic background with poor cardiovascular health was observed, supporting the importance of a thorough assessment of individuals presenting with syncope., Competing Interests: Conflicts of interest: The following authors are employees of deCODE genetics/Amgen, Inc.: Hildur M Aegisdottir, Rosa B Thorolfsdottir, Gardar Sveinbjornsson, Olafur A Stefansson, Bjarni Gunnarsson, Vinicius Tragante, Lilja Stefansdottir, Thorgeir E Thorgeirsson, Egil Ferkingstad, Gudmar Thorleifsson, Michael L Frigge, Kristjan E Hjorleifsson, Erna V Ivarsdottir, Anna Helgadottir, Solveig Gretarsdottir, Valgerdur Steinthorsdottir, Asmundur Oddsson, Hannes P Eggertsson, Gisli H Halldorsson, Patrick Sulem, Gudmundur Norddahl, Gudrun Rutsdottir, Gudmundur Thorgeirsson, David O Arnar, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hilma Holm, and Kari Stefansson. Karina Banasik and Søren Brunak acknowledge the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To estimate the risk of recurrent cardiovascular events in a real-world population of very high-risk Korean patients with prior myocardial infarction (MI), ischemic stroke (IS), or symptomatic peripheral artery disease (sPAD), similar to the Further cardiovascular OUtcomes Research with proprotein convertase subtilisin-kexin type 9 Inhibition in subjects with Elevated Risk (FOURIER) trial population., Methods: This retrospective study used the Asan Medical Center Heart Registry database built on electronic medical records (EMR) from 2000 to 2016. Patients with a history of clinically evident atherosclerotic cardiovascular disease (ASCVD) with multiple risk factors were followed up for 3 years. The primary endpoint was a composite of MI, stroke, hospitalization for unstable angina, coronary revascularization, and all-cause mortality., Results: Among 15,820 patients, the 3-year cumulative incidence of the composite primary endpoint was 15.3% and the 3-year incidence rate was 5.7 (95% CI 5.5-5.9) per 100 person-years. At individual endpoints, the rates of deaths, MI, and IS were 0.4 (0.3-0.4), 0.9 (0.8-0.9), and 0.8 (0.7-0.9), respectively. The risk of the primary endpoint did not differ significantly between recipients of different intensities of statin therapy. Low-density lipoprotein cholesterol (LDL-C) goals were only achieved in 24.4% of patients during the first year of follow-up., Conclusion: By analyzing EMR data representing routine practice in Korea, we found that patients with very high-risk ASCVD were at substantial risk of further cardiovascular events in 3 years. Given the observed risk of recurrent events with suboptimal lipid management by statin, additional treatment to control LDL-C might be necessary to reduce the burden of further cardiovascular events for very high-risk ASCVD patients., (© 2021. The Author(s).)

Purpose: Adults with atherosclerotic cardiovascular disease (ASCVD) are recommended high-intensity statins, with those at very high risk for recurrent events recommended adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor if their low-density lipoprotein cholesterol (LDL-C) is ≥70 mg/dL. We estimated the number of recurrent ASCVD events potentially averted if all adults in the United States (US) ≥45 years of age with ASCVD achieved an LDL-C <70 mg/dL., Methods: The number of US adults with ASCVD and LDL-C ≥70 mg/dL was estimated from the National Health and Nutrition Examination Survey 2009-2016 (n = 596). The 10-year cumulative incidence of recurrent ASCVD events was estimated from the REasons for Geographic And Racial Differences in Stroke study (n = 5390), weighted to the US population by age, race, and sex. The ASCVD risk reduction by achieving an LDL-C <70 mg/dL was estimated from meta-analyses of lipid-lowering treatment trials., Results: Overall, 14.7 (95% CI, 13.7-15.8) million US adults had ASCVD, of whom 11.6 (95% CI, 10.6-12.5) million had LDL-C ≥70 mg/dL. The 10-year cumulative incidence of ASCVD events was 24.3% (95% CI, 23.2-25.6%). We projected that 2.823 (95% CI, 2.543-3.091) million ASCVD events would occur over 10 years among US adults with ASCVD and LDL-C ≥70 mg/dL. Overall, 0.634 (95% CI, 0.542-0.737) million ASCVD events could potentially be averted if all US adults with ASCVD achieved and maintained LDL-C <70 mg/dL., Conclusion: A substantial number of recurrent ASCVD events could be averted over 10 years if all US adults with ASCVD achieved, and maintained, an LDL-C <70 mg/dL., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim of this study is to analyze the low-density lipoprotein cholesterol-lowering therapies in secondary prevention patients by analyzing their plasma low-density lipoprotein cholesterol levels, current treatment, considering their inadequate response to medications (as defined in current guidelines), and the requirement for a protein convertase subtilisin/kexin type 9 inhibitor., Methods: Delphi panel is used to seek expert consensus of experienced 12 cardiologists. A questionnaire consisting of 6 main questions is used to reflect the opinion of the expert panelists on the practices of low-density lipoprotein cholesterol-lowering therapies of patients with high and very high cardiovascular risk. Patients with atherosclerotic cardiovascular disease are covered in this present analysis., Results: According to expert opinion data, 18.6% of the patient population with atherosclerotic cardiovascular disease is estimated to have experienced recurrent vascular events. The current treatment of the patient population is 39.7% on high dose, 36.9% on low/moderate dose of statin, 13.1% on maximum tolerated dose statin+ezetimibe, and 1.2% on maximum tolerated dose statin+ezetimibe+protein convertase subtilisin/kexin type 9 inhibitor. The percentage of atherosclerotic cardiovascular disease patients with inadequate treatment response is estimated to be 20.2% in those using "maximum tolerated dose statin+ezetimibe." The proportion of patients who will need to be treated with a protein convertase subtilisin/kexin type 9 inhibitor increases as their low-density lipoprotein cholesterol levels rises from 9.1% in 70-99 mg/dL to 50.8% in ≥160 mg/dL for these patients., Conclusion: According to expert opinion, although a substantial proportion of patients with secondary prevention have not achieved low-density lipoprotein cholesterol goals, the use of protein convertase subtilisin/kexin type 9 inhibitors is very low. Since the questionnaire subject to panel discussion did not include any question elaborating the issue, the discrepancy between the recommendation of the related guidelines and Turkish practice needs further studies for the explanation.

Background: 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  ≥ $\ge $  70 mg/dL should take a high-intensity statin with ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i)., Objective/methods: 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., Results: Of those with eGFR <60 ml/min/1.73 m 2 , 21.6% (171/791) had intensification of LLT while 10.4% (82/791) had de-escalation of LLT. Notably, 61.6% (487/791) had no change in LLT regimen over 2 years. Statin use was 83.2% (785/944) at baseline and 80.1% (634/791) at 2 years. Statin/ezetimibe use increased from 2.9% (27/944) to 4.9% (39/791). Statin discontinuation at 2 years was greater with lower eGFR levels across all cohorts., Conclusion: Despite 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., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Digital technology is now an integral part of medicine. Tools for detecting, screening, diagnosis, and monitoring health-related parameters have improved patient care and enabled individuals to identify issues leading to better management of their own health. Wearable technologies have integrated sensors and can measure physical activity, heart rate and rhythm, and glucose and electrolytes. For individuals at risk, wearables or other devices may be useful for early detection of atrial fibrillation or sub-clinical states of cardiovascular disease, disease management of cardiovascular diseases such as hypertension and heart failure, and lifestyle modification. Health data are available from a multitude of sources, namely clinical, laboratory and imaging data, genetic profiles, wearables, implantable devices, patient-generated measurements, and social and environmental data. Artificial intelligence is needed to efficiently extract value from this constantly increasing volume and variety of data and to help in its interpretation. Indeed, it is not the acquisition of digital information, but rather the smart handling and analysis that is challenging. There are multiple stakeholder groups involved in the development and effective implementation of digital tools. While the needs of these groups may vary, they also have many commonalities, including the following: a desire for data privacy and security; the need for understandable, trustworthy, and transparent systems; standardized processes for regulatory and reimbursement assessments; and better ways of rapidly assessing value., Competing Interests: Conflict of interest: C.L. receives consulting fees from Medtronic, Boston Scientific, Abbott, and Biotronik; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Medtronic, Boston Scientific, Abbott, and Biotronik. H.W. has stock or stock options from Pfizer. R.P.K. has stock or stock options from Medtronic; and employment by Medtronic. D.A. has multiple patents including those for AliveCor, and GE assignments; stock or stock options from AliveCor, Inc.; and salary/officer position with AliveCor, Inc. M.R.C. receives consulting fees from AstraZeneca, Servier, Medtronic, and Abbott; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Servier, Medtronic, Abbott, and Bayer; served as Chair for ESC-Digital Health Committee (unpaid), Chair for Clinical Advisory Board of Pumping Marvellous Foundation (unpaid), Trustee of the Atrial Fibrillation Association (unpaid), and Non-executive Director of NICE from 2016-2020 (paid). T.D. receives consulting fees from Farapulse; payment or honoraria for lectures from Biotronik and Abbott; participation on a clinical events committee for Boston Scientific; served as a board member for the German Cardiology Society. P.F. participated on advisory board for Abbot, Medtronic, and Boston Scientific; IP, licensing fees, and equity stake via Mayo Clinic (employer) in AliveCor, EkoHealth, and Anuman. I.L. has stock or stock options from Amgen; and employment by Amgen. M.V.M. served as Co-Chair for the Consumer Technology Association (CTA)-American College of Cardiology (ACC) CV Technology Working Group; stock or stock options from Google; and employment by Google. L.R. supports for the present manuscript from Medtronic; employment by Medtronic. E.S. has stock or stock options from GE Healthcare; and employment by GE Vingmed Ultrasound AS. M.P.T. receives consulting fees from Medtronic, Abbott, Biotronik, Sanofi, Pfizer, Bayer, Myokardia, Johnson & Johnson, Milestone Pharmaceuticals, InCarda Pharmaceuticals, 100Plus, AliveCor, Actus Medical, and BrightInsight; grants from Bristol-Myers Squibb, American Heart Association, Apple, Bayer, and the US Food and Drug Administration; and editorship with JAMA Cardiology. J.P.S. receives consulting fees from Abbott, Biotronik, Boston Scientific, Cardiologs, CVRx, Cardiac Rhythm Group, EBR, Impulse Dynamics, Implicity, Medtronic, Medscape, Microport, New Century Health, Nopras, Orchestra BioMed, Octagos Health, and Sanofi. E.S. receives institutional research grants from the Stockholm County Council, the Åke Wiberg Foundation, and the Swedish Heart Foundation; consulting fees from Bayer, Bristol-Myers Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Johnson & Johnson, Merck Sharp & Dohme, Bristol-Myers Squibb-Pfizer, Boehringer-Ingelheim; participation on a data safety monitoring board or advisory board for Bristol-Myers Squibb-Pfizer; board membership for the European Heart Rhythm Association (EHRA), served as Chair of the Digital Committee for EHRA, and membership on the Digital Committee of the Heart Rhythm Society. M.W. supports for the present manuscript from Biotelemetry; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Biotelemetry; support for meeting attendance and/or travel from Biotelemetry; patents for Biotelemetry; stock or stock options from Biotelemetry. Other authors have none to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab reduced low-density lipoprotein cholesterol (LDL-C) and risk of cardiovascular events and was safe and well tolerated over a median of 2.2 years of follow-up. However, large-scale, long-term data are lacking., Methods: The parent FOURIER trial randomized 27 564 patients with atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on statin to evolocumab versus placebo. Patients completing FOURIER at participating sites were eligible to receive evolocumab in 2 open-label extension studies (FOURIER-OLE [FOURIER Open-Label Extension]) in the United States and Europe; primary analyses were pooled across studies. The primary end point was the incidence of adverse events. Lipid values and major adverse cardiovascular events were prospectively collected., Results: A total of 6635 patients were enrolled in FOURIER-OLE (3355 randomized to evolocumab and 3280 to placebo in the parent study). Median follow-up in FOURIER-OLE was 5.0 years; maximum exposure to evolocumab in parent plus FOURIER-OLE was 8.4 years. At 12 weeks in FOURIER-OLE, median LDL-C was 30 mg/dL, and 63.2% of patients achieved LDL-C <40 mg/dL on evolocumab. Incidences of serious adverse events, muscle-related events, new-onset diabetes, hemorrhagic stroke, and neurocognitive events with evolocumab long term did not exceed those for placebo-treated patients during the parent study and did not increase over time. During the FOURIER-OLE follow-up period, patients originally randomized in the parent trial to evolocumab versus placebo had a 15% lower risk of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization (hazard ratio, 0.85 [95% CI, 0.75-0.96]; P =0.008); a 20% lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80 [95% CI, 0.68-0.93]; P =0.003); and a 23% lower risk of cardiovascular death (hazard ratio, 0.77 [95% CI, 0.60-0.99]; P =0.04)., Conclusions: Long-term LDL-C lowering with evolocumab was associated with persistently low rates of adverse events for >8 years that did not exceed those observed in the original placebo arm during the parent study and led to further reductions in cardiovascular events compared with delayed treatment initiation., Registration: URL: https://www., Clinicaltrials: gov; Unique identifiers: NCT02867813 and NCT03080935.

Aims: Management of patients with recently decompensated heart failure by hospital services is expensive, complicated to plan, and not always effective. Telemedicine programmes in heart failure may improve the quality of care, but their effectiveness is poorly documented in real-world settings. The study aims to evaluate the impact of patient engagement in home-based telemonitoring for heart failure (SCAD programme) on rehospitalization and mortality rates., Methods and Results: A retrospective observational study was performed in 659 SCAD participants. SCAD is a patient-oriented service of home-based interactive telemonitoring offered to heart failure patients during hospitalization who agree to participate in a therapeutic education programme. Patients were telemonitored for at least 3 months, and rehospitalization and mortality were documented at 12 months and 5 years. During the telemonitoring period, patients provided daily information on health and lifestyle through an internet-based interface. Data were linked on a patient-by-patient basis between the SCAD database and the French national health insurance database (Système National des Données de Santé). Outcomes were compared as a function of use of the programme. Low, intermediate, and high users were classified by tercile of data return during telemonitoring. Patients were followed for a median of 32.9 months. Rehospitalization rates for cardiovascular disease decreased from 79.4% in the year preceding enrolment to 41.1% in the following year and from 52.8% to 18.8% for hospitalizations for heart failure. The 12 month mortality rate was 11.2%. Significant associations were observed between level of use of the SCAD programme and all-cause rehospitalization (P = 0.0085), rehospitalization for cardiovascular disease (P = 0.0010), rehospitalization for heart failure (27.8% in low users, 12.9% in intermediate users, and 13.5% in high users; P < 0.0001), and mortality (26.8%, 15.2%, and 15.9% respectively; P = 0.0157) in the 12 months following enrolment. The mean number of days alive outside hospital were 279 ± 111 in low users, 312 ± 90 in intermediate users, and 304 ± 100 in high users (P = 0.0022)., Conclusions: Educational home telemonitoring of patients with heart failure following hospitalization provides long-term clinical benefits in terms of rehospitalization and death in real-world settings, according to the level of use of the programme by the patient. These benefits would be expected to have a major impact on the burden of this disease. Low engagement in telemonitoring could be used as a signal of poor prognosis and taken into account in the management strategy., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Data support lipoprotein(a) (Lp[Lp(a)]) being a risk factor for atherosclerotic cardiovascular disease (ASCVD). Olpasiran is a small interfering RNA molecule that markedly reduces Lp(a) production in hepatocytes., Study Design: The Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study is a multicenter, randomized, double-blind, placebo-controlled dose-finding study in 281 subjects with established ASCVD and Lp(a) > 150 nmol/L. Patients were randomly allocated to one of 4 active subcutaneous doses of olpasiran (10 mg q12 weeks, 75 mg q12 weeks, 225 mg q 12 weeks, or 225 mg q24 weeks) or matched placebo. The primary objective is to evaluate the effects of olpasiran dosed every 12 weeks compared with placebo on the percent change in Lp(a) from baseline at 36 weeks. Enrollment is now complete and follow-up is ongoing., Conclusions: OCEAN(a)-DOSE trial is assessing the Lp(a)-lowering efficacy and safety of olpasiran. These data will be used to determine optimal dosing and design for a cardiovascular outcomes trial., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The growing elderly population worldwide represents a major challenge for caregivers, healthcare providers, and society. Older patients have a higher prevalence of cardiovascular (CV) disease, high rates of CV risk factors, and multiple age-related comorbidities. Although prevention and management strategies have been shown to be effective in older people, they continue to be under-used, and under-studied. In addition to hard endpoints, frailty, cognitive impairments, and patients' re-assessment of important outcomes (e.g. quality of life vs. longevity) are important aspects for older patients and emphasize the need to include a substantial proportion of older patients in CV clinical trials. To complement the often skewed age distribution in clinical trials, greater emphasis should be placed on real-world studies to assess longer-term outcomes, especially safety and quality of life outcomes. In the complex environment of the older patient, a multidisciplinary care team approach with the involvement of the individual patient in the decision-making process can help optimize prevention and management strategies. This article aims to demonstrate the growing burden of ageing in real life and illustrates the need to continue primary prevention to address CV risk factors. It summarizes factors to consider when choosing pharmacological and interventional treatments for the elderly and the need to consider quality of life and patient priorities when making decisions., Competing Interests: Conflict of interest: M.L.: honoraria from Bristol-Meyers Squibb, Pfizer, Sanofi, Boehringer Ingelheim, Daiichi Sankyo, and Edwards Lifescience; advisory board participation for Boehringer Ingelheim and Edwards Lifescience; and a leadership role (President) with a multi-hospital Institutional Review Board. M.N.: employment with Boehringer Ingelheim International J.-P.C.: Grants or contracts from Bristol-Myers Squibb, Medtronic, and Pfizer; and honoraria from Abbott, AstraZeneca, Boston Scientific, and Sanofi. G.D.: institutional grants to INSERM (RHU CARMMA) from Agence Nationale pour la Recherche (ANR). S.H.H.: consulting fees from Bristol-Meyers Squibb, Pfizer, Boehringer Ingelheim, Bayer, and Daiichi Sankyo; and honoraria from Bristol-Meyers Squibb, Pfizer, Boehringer Ingelheim, Bayer, and Daiichi Sankyo. D.E.O.: honoraria from Servier Canada. F.V.: research funding from Amgen. I.R.-L.: employment with and stock options from Amgen. And all other authors have no conflict of interest to declare., (Published on behalf of the European Society of Cardiology. All rights reserved. © The European Society of Cardiology 2022. For permissions, please email: journals.permissions@oup.com.)

Lipid-lowering medications comprise standard of care in the prevention of cardiovascular disease. This study examined the trends in the utilization of statin and non-statin medications in the Australian general population between 2013 and 2019. Pharmacoepidemiological analyses were performed using pharmacy dispensing data from Australian Pharmaceutical Benefits Scheme. One-year prevalence and incidence of statin and non-statin prescribing patterns were reported, and relative variations in prescribing examined via Poisson regression modelling. The one-year prevalence of statins' prescriptions decreased between 2013-2019 by 5.5% (from 25.0%-19.5%). Females were less likely than males to be prescribed statins (rate ratio [RR]=0.90, 95% confidence interval [CI] 0.89-0.91). The one-year prevalence of ezetimibe alone, and in combination with statins, increased consistently from 2013-2019 from 1.5%-3.6% (P<0.01) and 0.1%-1.1% (P<0.01), respectively. The prevalence was higher among those aged 61-80 years (RR=1.20, 95%CI 1.10-1.21) and those aged older than 80 years (RR=1.34, 95%CI 1.22-1.47), when compared to people aged <60 years. The incidence of ezetimibe prescriptions was highest in people aged 61-80 years (RR=1.36, 95%CI 1.31-1.41) compared to those aged <60 years. The one-year prevalence of proprotein convertase subtilisin/kexin type 9 inhibitor prescriptions was highest among those aged 46-60 years (RR=1.24, 95%CI 0.97-4.97) compared to people aged <46 and >60 years. Females were less likely than males to be prescribed a proprotein convertase subtilisin/kexin type 9 inhibitor (RR=0.87, 95%CI 0.75-0.98). Statins remain the most prevalent lipid-lowering medication prescribed in Australia. The prescribing of non-statin medications remains low, but is increasing., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: To evaluate the cost-effectiveness of evolocumab when added to standard of care lipid-lowering treatment (LLT) for patients with atherosclerotic cardiovascular disease (ASCVD) who cannot adequately control their low-density lipoprotein cholesterol (LDL-C) despite optimized LLT in Canada., Methods: An incremental cost-utility analysis was conducted using a Markov cohort state transition model adapted to the Canadian setting. Analyses were conducted from a public health and societal perspective using a lifetime time horizon for Canada. Scenario analyses were conducted on the basis of recommendations from the 2021 Canadian Cardiovascular Society (CCS) dyslipidemia guidelines., Results: In ASCVD patients with prior myocardial infarction (MI) and baseline LDL-C ≥ 1.8 mmol/L, adding evolocumab to optimized statin therapy with or without ezetimibe is associated with an incremental cost per quality-adjusted life year (QALY) gained of $66,453 CAD. Furthermore, for every 100 patients treated with evolocumab for lifetime, adding evolocumab to optimized LLT will prevent approximately 52 cardiovascular (CV) events, of which seven would be fatal. The results are generally robust using univariate and simultaneous variation in model input parameters. Scenario analyses for patient populations as per the CCS guidelines suggest that evolocumab added to optimized LLT may be considered cost-effective, given an incremental cost-effectiveness ratio (ICER) threshold of CAD$100,000 per QALY gained. Limitations associated with this analysis should be interpreted in the context of data and modeling assumptions used., Conclusion: Overall, this analysis supports reimbursement of evolocumab by payers in patients with ASCVD who cannot reach LDL-C thresholds despite optimized LLT to reduce unnecessary fatal and non-fatal CV events., (© 2022. The Author(s).)

Background It is unclear whether lipoprotein(a) is associated with coronary heart disease (CHD) and ischemic stroke events in White and Black adults with atherosclerotic cardiovascular disease (ASCVD). Methods and Results We conducted a case-cohort analysis, including Black and White REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants ≥45 years of age with prevalent ASCVD (ie, CHD or stroke) at baseline between 2003 and 2007. Baseline lipoprotein(a) molar concentration was measured in participants with ASCVD who experienced a CHD event by December 2017 (n=1166) or an ischemic stroke by September 2019 (n=492) and in a random subcohort of participants with prevalent ASCVD (n=1948). The hazard ratio (HR) for CHD events per 1 SD (1.5 units) higher log-transformed lipoprotein(a) was 1.26 (95% CI, 1.02-1.56) among Black participants and 1.16 (95% CI, 1.02-1.31) among White participants ( P value comparing HRs, 0.485). The HR for CHD events per 1 SD higher log-lipoprotein(a) within subgroups with hs-CRP (high-sensitivity C-reactive protein) ≥2 and <2 mg/L was 1.31 (95% CI, 0.99-1.73) and 1.23 (95% CI, 0.85-1.80), respectively ( P value comparing HRs, 0.836), among Black participants, and 1.07 (95% CI, 0.91-1.27) and 1.36 (95% CI, 1.10-1.70), respectively ( P value comparing HRs, 0.088), among White participants. There was no evidence that the association between lipoprotein(a) and CHD events differed by statin use. There was no evidence of an association between lipoprotein(a) and ischemic stroke events among Black or White participants. Conclusions Higher lipoprotein(a) levels were associated with an increased risk for CHD events in Black and White adults with ASCVD.

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 = 3626), a myocardial infarction (MI) other than a recent ACS (n = 7572), an ischemic stroke (n = 3551), or symptomatic peripheral artery disease (PAD, n = 5919). 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 1000 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., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: To estimate the health and economic burden of new and established cardiovascular disease from 2020 to 2029 in Australia., Methods and Results: A two-stage multistate dynamic model was developed to predict the burden of the incident and prevalent cardiovascular disease, for Australians 40-90 years old from 2020 to 2029. The model captured morbidity, mortality, years of life lived, quality-adjusted life years, healthcare costs, and productivity losses. Cardiovascular risk for the primary prevention population was derived using Australian demographic data and the Pooled Cohort Equation. Risk for the secondary prevention population was derived from the REACH registry. Input data for costs and utilities were extracted from published sources. All outcomes were annually discounted by 5%. A number of sensitivity analyses were undertaken to test the robustness of the study. Between 2020 and 2029, the model estimates 377 754 fatal and 991 375 non-fatal cardiovascular events. By 2029, 1 061 756 Australians will have prevalent cardiovascular disease (CVD). The population accrued 8 815 271 [95% uncertainty interval (UI) 8 805 083-8 841 432] years of life lived with CVD and 5 876 975 (5 551 484-6 226 045) QALYs. The total healthcare costs of CVD were projected to exceed Australian dollars (AUD) 61.89 (61.79-88.66) billion, and productivity losses will account for AUD 78.75 (49.40-295.25) billion, driving the total cost to surpass AUD 140.65 (123.13-370.23) billion., Conclusion: Cardiovascular disease in Australia has substantial impacts in terms of morbidity, mortality, and lost revenue to the healthcare system and the society. Our modelling provides important information for decision making in relation to the future burden of cardiovascular disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Oral lipid-lowering treatment (LLT) is the standard of care for patients with cardiovascular disease (CVD). However, insufficient treatment intensity and poor adherence can lead to suboptimal treatment benefit, rendering patients at increased risk of CVD., Aims: The objective of this study was to evaluate trends in LLT intensity and adherence in Sweden over time, and their association with major adverse cardiovascular events (MACE) after recent myocardial infarction (MI), and also to assess the impact of transition from secondary to primary care on intensity and adherence., Methods and Results: This retrospective observational cohort study used data from Swedish nationwide patient registers and included patients on LLT after an MI in the years 2010-2016 ( n = 50,298; mean age, 68 years; 69% men). LLT intensity was evaluated over time (overall, for 2010-2013 and for 2014-2016) as the proportion of patients prescribed low-, moderate-, and high-intensity LLT. Adherence was assessed as the proportion of days covered. A combined measure of intensity and adherence was also considered. Differences in treatment patterns and MACE were assessed. Initiation of high-intensity LLT increased over the two time periods studied (2010-2013, 32%; 2014-2016, 91%). Adherence varied by LLT intensity and was highest in patients receiving high-intensity LLT (>80%), especially during the first time period. Little change in treatment intensity or the combined measure of intensity and adherence was observed after transition to primary care. There was a significant association between the combined measure of intensity and adherence and MACE reduction (hazard ratio [95% confidence interval] per 10% increase in the combined measure: 0.84 [0.82-0.86]; P < 0.01)., Conclusion: The proportion of post-MI patients with high LLT intensity and adherence has increased in recent years, with little change after transfer from specialist to primary care. The combination of LLT intensity and adherence is important for preventing future cardiovascular events., Competing Interests: Maria K Svensson and Francesc Sorio were employed by Amgen when the study was conducted. Guillermo Villa is an employee and stockholder of Amgen. Margret Leósdóttir has received honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, MSD and Sanofi, investigator-initiated research grants from Amgen and Pfizer, and an honorarium from Amgen for work associated with this manuscript. Jonas Banefelt, Maria Lindh, and Alexander Rieem Dun are employed by Quantify Research, a contract research organization that provides consultancy services for the pharmaceutical industry. Anna Norhammar has received honoraria from AstraZeneca, Eli Lilly, Novo Nordisk, MSD, and Boehringer Ingelheim, and an honorarium from Amgen for worktime associated with this manuscript., (© 2022 The Author(s). Published by Upsala Medical Society.)

Objectives: To compare treatment patterns, risk factors and cardiovascular disease (CVD) event rates in the UK from 2008 to 2017., Design: Retrospective cohort study using the Clinical Practice Research Datalink., Setting: UK primary care., Participants: We selected 10 annual cohorts of patients with documented CVD receiving lipid-lowering therapy and the subsets with myocardial infarction (MI). Each cohort included patients ≥18 years old, with ≥1 year of medical history and ≥2 lipid-lowering therapy prescriptions in the prior year., Primary and Secondary Outcome Measures: For each annual cohort, we identified cardiovascular risk factors and lipid-lowering therapy and estimated the 1-year composite rate of fatal and non-fatal MI, ischaemic stroke (IS) or revascularisation., Results: The documented CVD cohort mean age was 71.6 years in 2008 (N=173 424) and 72.5 (N=94 418) in 2017; in the MI subset, mean age was 70.1 years in 2008 (N=38 999) and 70.4 in 2017 (N=25 900). Both populations had larger proportions of men. In the documented CVD cohort, the proportion receiving high-intensity lipid-lowering therapy from 2008 to 2017 doubled from 16% to 32%; in the MI subset, the increase was 20% to 48%. In the documented CVD cohort, the proportion of patients with low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L increased from 28% to 38%; in the MI subset, the proportion with LDL-C <1.8 mmol/L increased from 32% to 42%. The composite event rate per 100 person-years declined over time, from 2.5 to 2.0 in the documented CVD cohort, and from 3.7 to 2.8 in the MI subset. After excluding revascularisation from the composite outcome, the decline in the event rate in both populations was substantially attenuated., Conclusions: Despite an increase in high-intensity therapy use and a decline in revascularisation, more than half of patients did not receive high-intensity lipid-lowering therapy by 2017 and incidence rates of MI and IS remained virtually unchanged., Competing Interests: Competing interests: Amgen is a manufacturer of lipid-lowering therapies. ES and GV are full-time employees of Amgen (Europe) GmbH and hold stock of Amgen. DC and MI are full-time employees of Amgen and hold stock of Amgen. MD, MG and DL were employed by Outcomes Insights, who was funded by Amgen to conduct this research. JP received honoraria for providing consultant services to Amgen (Europe) GmbH., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A large number of patients are living with atherosclerotic cardiovascular (CV) disease and thus are at risk of life-threatening CV events., Hypothesis: This study evaluated the risk for a recurrent CV event or death in Finnish real-world data., Methods: Patients with an incident atherosclerotic CV event between 2012 and 2016 were included in this retrospective registry study and followed for recurrent CV events or death. The risk and risk factors of recurrent CV events or death and time from the first CV event to recurrence were assessed., Results: A total of 48,405 patients were followed from their first CV event. The event rate was 14.34 events per 100 patient-years. Multistate models suggested that at 5 years post index CV event, 41.5% of the patients had died or suffered a recurrent CV event. Death was the most common type of subsequent event (61.5%). After the first CV event, there were rapid increases both in recurrent CV events and deaths during the next 6 months. The subsequent CV event was usually of the same type as the first, which was of the cardiac or cerebrovascular cluster., Conclusions: The incidence of recurrent CV events and all-cause mortality was high in patients suffering from their first CV event, particularly during the first 6 months after the index event. Death was the most common subsequent event. The event rate accelerated after each additional CV event. This suggests that the acute treatment of the index event should be followed by prompt secondary prevention measures to achieve guideline-recommended goals as soon as possible., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Cardiovascular disease (CVD) is the most frequent cause of death in Austria. The European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT) in patients at high or very high CV risk. Lipid management and achievement of low-density lipoprotein cholesterol (LDL-C) goals in Austria have not recently been assessed., Methods: Subgroup analysis for Austria of a European 18 country, cross-sectional, observational study. Patients received LLT for primary (PP) or secondary prevention (SP). Data including LLT in the preceding 12 months and most recent LDL‑C were collected during a single visit between June 2017 and November 2018. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL‑C goal while receiving stabilized LLT was assessed., Results: A total of 293 patients were enrolled from 8 Austrian sites, of which 200 (PP = 104, SP = 96) received stabilized LLT at the LDL‑C measurement date. Overall, 58% (71% PP, 43% SP) and 38% (52% PP, 23% SP) achieved the risk-based 2016 and 2019 goals, respectively. Most patients received moderate-intensity statin monotherapy (46%), while 34% used high-intensity statin monotherapy. Combination therapy of moderate/high-intensity statin with ezetimibe (12%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors with statin ± ezetimibe (1%), was used infrequently., Conclusion: The current Austrian routine lipid management using mainly moderate-intensity or high-intensity statin monotherapy is insufficient to attain ESC/EAS guideline goals, in particular the more stringent 2019 recommendations, a situation comparable to other participating European countries. In addition to switching to and optimizing doses of high-intensity statins, a combination with ezetimibe or PCSK9 inhibitors will be needed in many cases., (© 2021. The Author(s).)

Objectives: We assessed healthcare resource utilization (HCRU) and costs of cardiovascular (CV) events in patients with a history of atherosclerotic cardiovascular disease (ASCVD) in Germany., Methods: We conducted a retrospective matched case-control study based on German claims data from 1 January 2012 to 31 December 2017 using the "Institute for Applied Health Research Berlin" (InGef) Research Database. Cases who had a myocardial infarction (MI), stroke and angina pectoris identified by ICD-10-GM codes between 1 January 2014 and 31 December 2016 were matched to event-free controls by an exact matching approach without replacement at a ratio of 1:2. Costs and HCRU were assessed in individual 1-year follow-up periods after the index event for the overall cohort and subgroups of MI cases and stroke cases., Results: The overall cohort consisted of a total of 14,169 cases with a CV index event matched to 28,338 controls. The mean age of the overall cohort was 73.3 years, 34.1% of the patients were female, 3,717 (26.2%) had an MI, and 3,752 (26.5%) had stroke. Following the index events, 12.2% of cases in the overall cohort, 12.6% of MI cases, and 8.7% of stroke cases experienced a recurrent CV event. CV cases had on average 1.7 more all-cause hospitalizations ( p  <0.001) and 6.1 more outpatient visits ( p  <0.001) during the 1-year follow-up period than did controls. In the MI and stroke subgroups, cases had on average 1.8 and 1.6 more all-cause hospitalizations and 7.0 and 4.0 more outpatient visits, respectively (differences were statistically significant). Compared to controls, cases incurred on average higher total healthcare costs: by €11,898 for overall cases, by €16,349 for MI, and by €14,360 in stroke cases (overall: p  <0.001; MI: p  <0.001; stroke: p  <0.001)., Conclusion: CV events in ASCVD patients pose a considerable clinical burden on patients and cause significant costs for the German statutory healthcare system.

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in Italy, accounting for 22% of total deaths. Lowering low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of cardiovascular (CV) events; thus, lipid-lowering therapy (LLT) is the first-line treatment for patients with ASCVD and hypercholesterolaemia. However, many patients with ASCVD fail to reach LDL-C treatment thresholds, leaving them at greater risk of CV events. Inpatient care accounts for 51% of total expenditure on cardiovascular disease in the European Union, but healthcare resource utilization (HCRU) data for ASCVD in Italy is limited., Methods: The study analysed healthcare claims data for 17,881 patients with acute coronary syndrome, ischemic stroke or peripheral artery disease from the Umbria 2 and Marche regions of Italy. LLT treatment patterns and CV event rates were collected and HCRU estimated in the year before and after the index event., Results: High-intensity LLTs were prescribed to 44.3% of patients and 49.6% received moderate-/low-intensity LLTs during the 6 months after the index event. The first year CV event rate was 18.0/100 patient-years for patients receiving high-intensity LLTs and 17.2/100 patient-years for those on moderate-/low-intensity LLTs. Higher costs were associated with patients untreated with LLT 6 months post-index event (€8323) than patients prescribed high-intensity (€6278) or moderate-/low-intensity LLTs (€6270). Hospitalization accounted for most of the total costs., Conclusions: This study found that CV events in secondary prevention Italian patients are associated with substantial HCRU and costs. More intensive LDL-C lowering can prevent CV events, easing the financial burden on the healthcare system., (© 2021. The Author(s).)

Genetic data do not provide evidence for SOST inhibition causing cardiovascular disease.

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use 1 . Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels 2 , heart disease remains the leading cause of death worldwide 3 . Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS 4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns 24 . Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine 25 , we anticipate that increased diversity of participants will lead to more accurate and equitable 26 application of polygenic scores in clinical practice., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality worldwide. Data from Canadian populations regarding the burden of ASCVD are limited. Therefore, we describe the 5-year period prevalence of ASCVD and subsequent major adverse cardiovascular event (MACE) outcomes among patients with ASCVD in Alberta, Canada., Methods: A retrospective, observational study was conducted by linking provincial health services data, vital statistics, and pharmaceutical dispenses data. Five-year period prevalence of clinical ASCVD was captured between 2011 and 2016, and a cohort of adult patients with an initial clinical ASCVD event were identified between 2012 and 2016. One-year incidence rates (IRs) of subsequent MACE outcomes were calculated as composite and individual measures. A subgroup of patients with acute myocardial infarction (AMI) as their index event was examined., Results: There were 198 573 patients (mean [standard deviation] age: 63.9 [15.6] years; 56.6% males) identified with clinical ASCVD between 2012 and 2016. Overall, the 5-year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons and the 1-year IR for a primary MACE outcome was 6.15 (95% confidence interval [CI]: 6.03-6.26) per 100 person-years. Among the ASCVD cohort, 9465 had an AMI as their index event and the IR for a primary MACE outcome was 14.30 (95% CI: 13.45-15.20) per 100 person-years., Conclusions: This study found that the prevalence of ASCVD and the rate of subsequent MACE outcomes 1 year following the initial ASCVD event are substantial, particularly among patients with an AMI. Secondary prevention strategies aimed at lowering this risk are needed for patients with ASCVD., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Migraine has been associated with cardiovascular disease (CVD) events among middle-aged adults. The objective of this study was to determine the risk for ischemic stroke and coronary heart disease (CHD) events among older adults with versus without migraine., Methods: This retrospective cohort study was conducted using data from US adults ≥66 years of age with Medicare health insurance between 2008 and 2017. After stratification by history of CVD, patients with a history of migraine were matched 1:4 to those without a history of migraine, based on calendar year, age, and sex. Patients were followed through December 31, 2017 for ischemic stroke and CHD events including myocardial infarction or coronary revascularization. All analyses were done separately for patients with and without a history of CVD., Results: Among patients without a history of CVD (n = 109,950 including n = 21,990 with migraine and n = 87,960 without migraine), 1789 had an ischemic stroke and 3552 had a CHD event. The adjusted hazard ratio (HR) among patients with versus without migraine was 1.20 (95% confidence interval [95%CI], 1.07-1.35) for ischemic stroke and 1.02 (95%CI, 0.93-1.11) for CHD events. Compared to patients without migraine, those with migraine who were taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.43 [95%CI, 1.20-1.69]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.79 [95%CI, 0.67-0.93]). Among patients with a history of CVD (n = 79,515 including n = 15,903 with migraine and n = 63,612 without migraine), 2960 had an ischemic stroke and 7981 had a CHD event. The adjusted HRs (95%CI) for ischemic stroke and CHD events associated with migraine were 1.27 (1.17-1.39) and 0.99 (0.93-1.05), respectively. Patients with migraine taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.21 [95%CI, 1.07-1.36]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.83 [95%CI, 0.72-0.95]), each versus those without migraine., Conclusions: Older adults with migraine are at increased risk for ischemic stroke. The risk for ischemic stroke among older adults with migraine may differ by migraine medication classes., (© 2021. The Author(s).)

Objective: Familial hypercholesterolemia (FH) is traditionally defined as a monogenic disease characterized by severely elevated LDL-C (low-density lipoprotein cholesterol) levels. In practice, FH is commonly a clinical diagnosis without confirmation of a causative mutation. In this study, we sought to characterize and compare monogenic and clinically defined FH in a large sample of Icelanders. Approach and Results: We whole-genome sequenced 49 962 Icelanders and imputed the identified variants into an overall sample of 166 281 chip-genotyped Icelanders. We identified 20 FH mutations in LDLR, APOB, and PCSK9 with combined prevalence of 1 in 836. Monogenic FH was associated with severely elevated LDL-C levels and increased risk of premature coronary disease, aortic valve stenosis, and high burden of coronary atherosclerosis. We used a modified version of the Dutch Lipid Clinic Network criteria to screen for the clinical FH phenotype among living adult participants (N=79 058). Clinical FH was found in 2.2% of participants, of whom only 5.2% had monogenic FH. Mutation-negative clinical FH has a strong polygenic basis. Both individuals with monogenic FH and individuals with mutation-negative clinical FH were markedly undertreated with cholesterol-lowering medications and only a minority attained an LDL-C target of <2.6 mmol/L (<100 mg/dL; 11.0% and 24.9%, respectively) or <1.8 mmol/L (<70 mg/dL; 0.0% and 5.2%, respectively), as recommended for primary prevention by European Society of Cardiology/European Atherosclerosis Society cholesterol guidelines. Conclusions: Clinically defined FH is a relatively common phenotype that is explained by monogenic FH in only a minority of cases. Both monogenic and clinical FH confer high cardiovascular risk but are markedly undertreated.

Background and Aims: Central and Eastern Europe (CEE) is a largely understudied region, despite having the highest cardiovascular disease mortality in Europe. This analysis aimed to assess the proportion of patients in CEE who achieved their LDL-C goals based on individual cardiovascular risk recommended by the 2016 and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines., Methods: The DA VINCI study was a cross-sectional observational study of primary and secondary prevention patients receiving lipid-lowering therapy across Europe between June 2017 and November 2018., Results: In total, 2154 patients were enrolled from the Czech Republic (n = 509), Hungary (n = 319), Poland (n = 460), Romania (n = 259), Slovakia (n = 123) and Ukraine (n = 484). At LDL-C measurement, most patients were on either moderate- or high-intensity statin monotherapy (53% and 32%, respectively). Despite this, only 44% of patients achieved risk-based LDL-C goals recommended by the 2016 ESC/EAS guidelines, ranging from 21% in Ukraine to 50% in Hungary and Romania. Only 24% of patients overall achieved the risk-based LDL-C goals recommended by the 2019 ESC/EAS guidelines, ranging from 11% in Ukraine to 32% in Poland., Conclusions: Among patients receiving lipid-lowering therapy, more than half did not achieve their 2016 LDL-C goals. In one of the first comparative analyses evaluating 2019 risk-based goal attainment among countries in CEE, three-quarters of patients did not meet their 2019 LDL-C goals, highlighting a significant gap between guidelines and clinical practice for lipid management in CEE., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: There is limited real-world evidence around use of proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) among US older adults. This study examined baseline characteristics of fee-for-service (FFS) Medicare beneficiaries newly initiating PCSK9i therapy during the period immediately following market availability., Methods: This cross-sectional study used Medicare claims (2013-2016) to identify 5051 FFS Medicare beneficiaries who filled ≥ 1 PCSK9i prescription between August 2015 and December 2016. We analyzed patient demographics, clinical characteristics, and baseline healthcare expenditures in the 12-month period prior to PCSK9i initiation, for these beneficiaries., Results: Most beneficiaries initiating PCSK9i were female (57%), < 75 years of age (61%), white (89%), and lived in metropolitan areas (83%). At baseline, these PCSK9i initiators had 6 chronic conditions on average, with conditions such as hyperlipidemia, hypertension, and ischemic heart disease being most prevalent. Approximately 88% had a diagnosis of atherosclerotic cardiovascular disease (ASCVD), and 14% experienced acute cardiovascular events during the 12-month baseline period. Use of any statin and/or ezetimibe ranged from 54 to 76% in the 6-month and 24-month baseline period. Their total annual Medicare expenditures averaged US$17,552, of which most were attributable to ambulatory care and prescription use, in the 12-month baseline period., Conclusion: High burden of cardiovascular conditions and prescription expenditures at baseline were common among FFS beneficiaries initiating PCSK9i therapy. These findings suggest that physicians prescribe PCSK9i to elderly patients at high risk for adverse cardiovascular events. Considering the evolving treatment landscape, PCSK9i utilization might increase in Medicare., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The risk for subsequent major cardiovascular (CV) events among patients with very high-risk (VHR) atherosclerotic CV disease (ASCVD) remains to be fully elucidated., Hypothesis: We 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., Methods: This 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., Results: Among 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., Conclusions: Most 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., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)