A retrospective nationwide analysis of evolocumab use in Sweden and its effect on low-density lipoprotein cholesterol levels.

Background: Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduces low-density lipoprotein cholesterol (LDL-C) levels and decreases the incidence of major ischaemic events in clinical trials. However, less is known about the efficacy of PCSK9 inhibition in clinical practice. This study aimed to describe the change in LDL-C levels over time and LDL-C goal achievement in patients with/without atherosclerotic cardiovascular disease (ASCVD), who were prescribed evolocumab in clinical practice, and to describe adherence to and persistence with treatment. Methods: Patients in Sweden with at least one evolocumab prescription filled between July 2015 and May 2020 were included. Medical history and lipid-lowering therapy (LLT) were sourced from national registries. LDL-C levels before and after treatment initiation were assessed using medical records. Persistence with and adherence to evolocumab and oral LLT were assessed up to 12 months after treatment initiation using the refill-gap method and proportion of days covered, respectively. Results: Of the 2,360 patients with at least one prescription for evolocumab, 2,341 were included; 1,858 had ASCVD. Persistence with (76%) and adherence to (86%) evolocumab were high throughout the 12 months following initiation. Mean LDL-C levels decreased by 53% (95% confidence interval [CI]: 51-55%) in patients adherent to evolocumab (n = 567) and 59% (95% CI: 55-63%) in patients adherent to evolocumab and oral LLT (n = 186). Similar reductions in LDL-C were observed in patients with/without ASCVD. Reduced LDL-C levels remained stable during follow-up. Amongst patients adherent to evolocumab and those adherent to evolocumab and oral LLT, 23 and 55% achieved the LDL-C goal of <1.4 mmol/L, respectively. Conclusions: The evolocumab LDL-C-lowering effect observed in clinical trials was confirmed in clinical practice in Sweden, particularly in patients also treated with oral LLT. During follow-up, adherence to and persistence with evolocumab were high, with stable reduced levels of LDL-C during observation.

Optimal implementation of the 2019 ESC/EAS dyslipidaemia guidelines in patients with and without atherosclerotic cardiovascular disease across Europe: a simulation based on the DA VINCI study.

Background: The impact of the stepwise implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) treatment algorithm on low-density lipoprotein cholesterol (LDL-C) goal attainment was simulated in patients from the DA VINCI study. Methods: Monte Carlo simulation was used to evaluate treatment optimisation scenarios, based on a patient's risk category: statin intensification (step 1), addition of ezetimibe (step 2), and addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (step 3). Residual cardiovascular risk and predicted relative and absolute risk reduction (RRR and ARR) in cardiovascular events were assessed. Findings: In DA VINCI, 2482 patients did not achieve their 2019 ESC/EAS LDL-C goals and were included in the simulation. In patients without atherosclerotic cardiovascular disease (ASCVD) (n = 962), 27.0% (n = 259) and 57.0% (n = 548) are likely to achieve their LDL-C goals at step 1 and step 2, respectively. Of those at very high risk without ASCVD (n = 74), 88.1% (n = 65) are likely to achieve their LDL-C goals at step 3. In patients with ASCVD (n = 1520), 12.0% (n = 183), 42.1% (n = 641) and 93.2% (n = 1416) are likely to achieve their LDL-C goals at steps 1, 2 and 3, respectively. In patients with and without ASCVD, treatment optimisation may result in mean simulated RRR of 24.0% and 17.7%, respectively, and ARR of 8.1% and 2.6%, respectively. Interpretation: Most patients at high cardiovascular risk are unlikely to achieve LDL-C goals through statin optimisation and ezetimibe, and will require a PCSK9 inhibitor, leading to greater reduction in cardiovascular risk. Funding: Amgen.

European Physician Survey Characterizing the Clinical Pathway and Treatment Patterns of Patients Post-Myocardial Infarction.

INTRODUCTION: The 2019 European Society of Cardiology and European Atherosclerosis Society (2019 ESC/EAS) guidelines stress the importance of managing low-density lipoprotein cholesterol (LDL-C) after myocardial infarction (MI) to reduce the risk of cardiovascular events. Information on guideline implementation is limited. The aim of this survey was to describe current clinical practice regarding LDL-C management in the first year post-MI across Europe, improving understanding of the role of ESC/EAS guidelines on clinical practice. METHODS: A qualitative web-based cross-sectional physician survey about the patient pathway and LDL-C management post-MI was conducted in 360 physicians from France, Italy, Germany, The Netherlands, Spain, and the UK (n = 60/country) between December 2019 and June 2020. Secondary and primary care physicians (SCPs/PCPs) described their experiences treating patients post-MI over the preceding 2 months. RESULTS: Physicians reported that on average 90.7% of patients not prescribed lipid-lowering therapy (LLT) before an MI initiated LLT as inpatients; for patients already taking LLT, treatment was intensified for 64.7% of inpatients post-MI. SCPs reported prescribing higher-intensity statins and/or ezetimibe for between 72.3% (Italy) and 88.6% (UK) of patients post-MI. More than 80.0% of SCPs and 51.2% of PCPs stated that they would initiate a change in LLT immediately if patients did not achieve their LDL-C treatment goal by 12 weeks post-MI; 82.0% of SCPs and 55.1% of PCPs reported referring to 2019 ESC/EAS guidelines for management of patients post-MI. Barriers to initiating PCSK9 inhibitors (PCSK9is) included prior prescription of a maximally tolerated dose of statin (49.4%) and/or ezetimibe (38.9%), requirement to reach threshold LDL-C levels (44.9%), and pre-authorization requirements (30.4%). CONCLUSION: Differences in clinical practice post-MI were reported across the countries surveyed, including divergence between 2019 ESC/EAS and local guidelines. Increased use of innovative medicines to achieve LDL-C goals should reduce risk of subsequent cardiovascular events in very high-risk patients post-MI.

Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study From DA VINCI.

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.

Network Meta-Analysis of Randomized Trials Evaluating the Comparative Efficacy of Lipid-Lowering Therapies Added to Maximally Tolerated Statins for the Reduction of Low-Density Lipoprotein Cholesterol.

Background Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular risk. However, appropriate doses of statin therapy are often insufficient to reduce LDL-C in accordance with current guidelines. In such cases, treatment could be supplemented with nonstatin lipid-lowering therapy. Methods and Results A systematic literature review and network meta-analysis were conducted on randomized controlled trials of nonstatin lipid-lowering therapy added to maximally tolerated statins, including statin-intolerant patients. The primary objective was to assess relative efficacy of nonstatin lipid-lowering therapy in reducing LDL-C levels at week 12. Secondary objectives included the following: LDL-C level reduction at week 24 and change in non-high-density lipoprotein cholesterol and apolipoprotein B at week 12. There were 48 randomized controlled trials included in the primary network meta-analysis. All nonstatin agents significantly reduced LDL-C from baseline versus placebo, regardless of background therapy. At week 12, evolocumab, 140 mg every 2 weeks (Q2W)/420 mg once a month, and alirocumab, 150 mg Q2W, were the most efficacious regimens, followed by alirocumab, 75 mg Q2W, alirocumab, 300 mg once a month, inclisiran, bempedoic acid/ezetimibe fixed-dose combination, and ezetimibe and bempedoic acid used as monotherapies. Primary end point results were generally consistent at week 24, and for other lipid end points at week 12. Conclusions Evolocumab, 140 mg Q2W/420 mg once a month, and alirocumab, 150 mg Q2W, were consistently the most efficacious nonstatin regimens when added to maximally tolerated statins to lower LDL-C, non-high-density lipoprotein cholesterol, and apolipoprotein B levels and facilitate attainment of guideline-recommended risk-stratified lipoprotein levels.

Effects of lipid-lowering treatment intensity and adherence on cardiovascular outcomes in patients with a recent myocardial infarction: a Swedish register-based study.

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.

Achieving Lower LDL-C Levels After a Recent Myocardial Infarction Might Be Associated with Lower Healthcare Resource Use and Costs in Spain.

INTRODUCTION: There is little evidence on the relationship between achieved low-density lipoprotein cholesterol (LDL-C) levels and costs in patients on lipid-lowering therapy (LLT). We described healthcare resource use and costs (direct and indirect) by achieved LDL-C in patients receiving LLT after a recent myocardial infarction (MI) in Spain. METHODS: This was a retrospective observational study of anonymized electronic medical records from seven regions in Spain (BIG-PAC® database; n = 1.9 million). Eligible patients were adults (≥ 18 years) hospitalized for an MI between January 2015 and December 2017, treated with a statin and/or ezetimibe, and having recorded LDL-C values at baseline and during follow-up. Healthcare resource use and direct and indirect costs (in 2018, €) were described by achieved LDL-C levels during a follow-up of 18 months. RESULTS: Of 6025 patients (mean age, 69.7 years; 77% male), only 11% achieved LDL-C goals as defined in the 2016 ESC/EAS guidelines (< 70 mg/dL), and just 1% reached the lower target (< 55 mg/dL) in the current 2019 guidelines. Achieving lower LDL-C levels translated to lower healthcare resource use and costs. Mean total (direct and indirect) costs ranged from €5044 for patients with LDL-C < 55 mg/dL to €7567 for patients with LDL-C ≥ 130 mg/dL. CONCLUSION: Very few patients achieved recommended LDL-C goals despite using LLT. Achieving lower LDL-C levels after an MI might be associated with lower healthcare resource use and costs. Use of more intensive LLT, leading to greater reductions in LDL-C, could therefore be beneficial both from a clinical and an economic perspective.

Longitudinal evaluation of treatment patterns, risk factors and outcomes in patients with cardiovascular disease treated with lipid-lowering therapy in the UK.

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.

Clinical characterization of patients with inflammatory myopathy in 2 tertiary care hospitals in Colombia: A descriptive survey / Caracterización clínica de pacientes con miopatía inflamatoria en 2 instituciones de alta complejidad en Colombia: estudio descriptivo

ABSTRACT Background: There is little information on inflammatory myopathies in Colombia. The objective was to identify the demographic and clinical characteristics of these patients in two tertiary care hospitals between 2010 and 2015. Materials and methods: A descriptive, retrospective survey was carried out, by reviewing medical records and obtaining information on demographic and clinical variables. The qualitative variables were expressed using absolute and relative frequencies, and the quantitative with mean and standard deviation (SD), or median with interquartile ranges (IQR), depending on data distribution. The IBM SPSS 22 statistical package was used. Results: A total of 105 patients with a mean age of 50.4 years (SD: 15.1) were included, with 76 (72.4%) women. In total, 50 subjects (48.5%) had a definitive diagnosis. The most common inflammatory myopathy was dermatomyositis (n = 66; 62.9%). The skin was the most commonly affected organ (n=66; 62.9%). Muscle weakness was present in 60 individuals (57.1%). The most frequent alarm sign was swallowing disorder (n = 28; 26.7%). Creatine phosphokinase was higher in polymyositis, with a median of 1800IU/L (IQR: 365-6157). The most widely used drugs were glucocorticoids (n = 83; 79%). Some patients were refractory to immunosuppressive treatment, mainly in antisynthetase syndrome (n = 5; 35.7%). Five patients (4.8%) died of infections (pneumonia and bacteraemia). Conclusions: In this cohort, the most common entity was dermatomyositis, and the most affected organ was the skin. There was a significant presentation of warning signs, refractoriness to immunosuppressive treatment, and lower muscle enzyme values compared to other cohorts. Mortality was mainly due to infectious complications.

RESUMEN Introducción: Existe poca información sobre las miopatías inflamatorias en Colombia. El obje tivo fue identificar las características demográficas y clínicas de estos pacientes en dos instituciones de alta complejidad entre los arios 2010 y 2015. Materiales y métodos: Se realizó un estudio descriptivo y retrospectivo. Mediante revisión de registros médicos, se obtuvo información sobre variables demográficas y clínicas. Las variables cualitativas se expresaron mediante frecuencias absolutas y relativas, y las cuantitativas con media y desviación estándar (DE) o mediana con rangos intercuartílicos (RIQ), dependiendo de la distribución de los datos. Se utilizó el paquete estadístico IBM SPSS® v.22. Resultados: Se incluyeron 105 pacientes con edad promedio de 50,4 años (DE: 15,1); 76 mujeres (72,4%). En total, 50 sujetos (48,5%) tuvieron diagnóstico definitivo. La miopa tía inflamatoria más común fue dermatomiositis (n = 66; 62,9%). La piel fue el órgano más comúnmente afectado (n = 66; 62,9%). La debilidad muscular estuvo presente en 60 individuos (57,1%). El signo de alarma más frecuente fue el trastorno de la deglución (n = 28; 26,7%). La creatinfosfoquinasa tuvo mayor elevación en polimiositis con una mediana de 1.800 Ul/l (RIQ: 365-6.157). Los medicamentos más utilizados fueron los glucocorticoides (n = 83; 79%). Hubo refractariedad al tratamiento inmunosupresor, principalmente en síndrome antisintetasa (n = 5; 35,7%). Cinco pacientes (4,8%) murieron por infecciones (neumonía y bacteriemia). Conclusiones: En esta cohorte, la entidad más común fue la dermatomiositis y el órgano más afectado fue la piel. Hubo presentación relevante de signos de alarma, refractariedad al tratamiento inmunosupresor y valores de enzimas musculares menores comparados con otras cohortes. La mortalidad fue principalmente por complicaciones infecciosas.

Low-density lipoprotein cholesterol levels exceed the recommended European threshold for PCSK9i initiation: lessons from the HEYMANS study.

AIMS: To describe the characteristics of patients receiving evolocumab in clinical practice across 12 European countries and simulate the association between low-density lipoprotein cholesterol (LDL-C) reduction and cardiovascular (CV) risk reduction. METHODS AND RESULTS: The characteristics of hyperlipidaemic patients at initiation of evolocumab and treatment patterns study-HEYMANS (n = 1952) is a prospective registry of patients ≥18 years old who initiated evolocumab from 1 August 2015 onwards. Mean (standard deviation) age was 60 (10.8), 85% had a prior CV event, 45% were diagnosed with familial hypercholesterolaemia (FH), and 60% had statin intolerance. At evolocumab initiation, 43% were receiving any statin, 16% were receiving ezetimibe without statin, and 41% received no background lipid-lowering therapy (LLT), with LDL-C levels reflecting local proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) reimbursement criteria. Median LDL-C decreased from 3.98 to 1.63 mmol/L within 3 months of evolocumab initiation and was maintained over 24 months. Overall, 58% achieved risk-based 2019 European Society of Cardiology/European Atherosclerosis Society LDL-C goals but that proportion was higher (68%) in patients receiving background LLT compared with those not receiving background LLT (44%). In patients with atherosclerotic cardiovascular disease without FH, the simulated relative CV risk reduction associated with evolocumab treatment was 34% (25-44%). CONCLUSION: Across Europe, LDL-C levels at evolocumab initiation were three times higher than recommended thresholds for PCSK9i initiation, reflecting disparities between implementation and guidelines. More patients attained risk-based LDL-C goals when receiving evolocumab in combination with LLT vs. those not receiving combination therapy. Population health could be improved and LDL-C goals better attained if LDL-C thresholds for PCSK9i reimbursement were lowered, enabling more patients to receive combination therapy when needed.

Cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab in patients with a history of myocardial infarction in Sweden.

AIMS: To assess the cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to standard-of-care lipid-lowering treatment [maximum tolerated dose (MTD) of statin and ezetimibe] in Swedish patients with a history of myocardial infarction (MI). METHODS AND RESULTS: Cost-effectiveness was evaluated using a Markov model based on Swedish observational data on cardiovascular event rates and efficacy from the FOURIER trial. Three risk profiles were considered: recent MI in the previous year; history of MI with a risk factor; and history of MI with a second event within 2 years. For each population, three minimum baseline low-density lipoprotein cholesterol (LDL-C) levels were considered: 2.5 mmol/L (≈100 mg/dL), based on the current reimbursement recommendation in Sweden; 1.8 mmol/L (≈70 mg/dL), based on 2016 ESC/EAS guidelines; and 1.4 mmol/L (≈55 mg/dL), or 1.0 mmol/L (≈40 mg/dL) for MI with a second event, based on 2019 ESC/EAS guidelines. Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab was associated with increased quality-adjusted life-years and costs vs. standard-of-care therapy. Incremental cost-effectiveness ratios (ICERs) were below SEK700 000 (∼€66 500), the generally accepted willingness-to-pay threshold in Sweden, for minimum LDL-C levels of 2.3 (recent MI), 1.7 (MI with a risk factor), and 1.7 mmol/L (MI with a second event). Sensitivity analyses demonstrated that base-case results were robust to changes in model parameters. CONCLUSION: Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to MTD of statin and ezetimibe may be considered cost-effective at its list price for minimum LDL-C levels of 1.7-2.3 mmol/L, depending on risk profile, with ICERs below the accepted willingness-to-pay threshold in Sweden.

Patient characteristics and acute cardiovascular event rates among patients with very high-risk and non-very high-risk atherosclerotic cardiovascular disease.

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.

Screening and treatment of familial hypercholesterolemia in a French sample of ambulatory care patients: A retrospective longitudinal cohort study.

BACKGROUND AND AIMS: Untreated Familial Hypercholesterolemia (FH) leads to premature morbidity and mortality. In France, its epidemiology and management are understudied in ambulatory care. We described the clinical profile, pharmacological management, and clinical outcomes in a French sample of FH patients. METHODS: This was a retrospective longitudinal study on patients from The Health Improvement Network (THIN®) database in France, between October 2016-June 2019. Patients ≥18 years, with probable/definite FH based on the Dutch Lipid Clinic Network (DLCN) criteria were included. Baseline characteristics, lipid profile, lipid-lowering therapy (LLT), low-density lipoprotein-cholesterol (LDL-C) goal achievement; and disease management at 6-month of follow-up were analyzed. RESULTS: 116 patients with probable (n = 70)/definite (n = 46) FH were included (mean age:57.8±14.0 years; 56.0% women; 9.5% with personal history of cardiovascular events); 90 patients had data available at follow-up. At baseline, 77.6% of patients had LDL-C>190 mg/dL, 27.6% were not receiving LLTs, 37.9% received statins alone, 20.7% statins with other LLTs, and 7.7% other LLTs. High-intensity statins were prescribed to 11.2% of patients, 30.2% received moderate-intensity statins, and 8.6% low-intensity statins. Only 6.0% of patients achieved LDL-C goal. At 6-month of follow-up, statins discontinuation and switching were 22.7% and 2.3%, respectively. None of the patients received proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors at baseline nor follow-up. CONCLUSIONS: Despite the existence of effective LLTs, FH patients are suboptimally-treated, do not achieve LDL-C goal, and exhibit worsened pharmacological management over time. Future studies with longer follow-up periods and assessment of factors affecting LDL-C management, including lifestyle and diet, are needed.

Cardiovascular Event Rates After Myocardial Infarction or Ischaemic Stroke in Patients with Additional Risk Factors: A Retrospective Population-Based Cohort Study.

INTRODUCTION: The impact of additional risk factors on major cardiovascular event (MACE) rates in patients with a history of myocardial infarction (MI) or ischaemic stroke (IS) treated with statins is not well defined. METHODS: In this retrospective population-based cohort study, patients with a history of MI or IS treated with moderate- or high-intensity statins were identified using Swedish national register data. Patients were incident (index event between July 2006 and December 2014 and followed from diagnosis) or prevalent (MI or IS before July 2006 and followed thereafter). Four subgroups were defined on the basis of additional risk factors associated with increased cardiovascular risk: diabetes mellitus with target organ damage; chronic kidney disease stages 3-4; index event within 2 years after prior MI or IS; and polyvascular disease. First and total MACE rates (i.e. MI, IS, or cardiovascular death) were calculated, and first MACE 10-year risks (prevalent cohort only) were predicted. RESULTS: Numerically, MACE rates in subgroups were 1.5-3 times higher than in overall populations, and were highest in the 2 years after the index event. First MACE rates in the additional risk factor subgroups were 17.2-33.5 per 100 person-years for the incident cohorts and 9.9-13.2 per 100 person-years for the prevalent cohorts. Total MACE rates per 100 person-years were 20.1-39.8 per 100 person-years and 12.4-17.6 per 100 person-years, respectively. CONCLUSION: Despite previous use of moderate- or high-intensity statins, patients with a history of MI or IS, and additional risk factors remain at very high cardiovascular risk.

Prevalencia de ß-lactamasas de espectro extendido en Escherichia coli y Klebsiella pneumoniae identificados en una institución de salud en Barranquilla / Prevalence of extended spectrum ß-lactamases in Escherichia coli and Klebsiella pneumoniae identified in a health institution in Barranquilla

Introducción: Uno de los mecanismos de resistencia en Gram negativos es la producción de ß-lactamasas de espectro extendido (BLEE), capaces de otorgar resistencia a penicilinas y cefalosporinas. Objetivo. Determinar la prevalencia de ß-lactamasas de amplio espectro en aislamientos de Escherichia coli y Klebsiella pneumoniae identificados en una institución de salud. Metodología: Se tomaron los resultados del laboratorio clínico de los pacientes hospitalizados por enfermedades infecciosas identificados en un hospital de 4º nivel de complejidad en Barranquilla durante el año 2018 asociados a E. coli y K. pneumoniae, y se evaluó la resistencia de los mismos. Resultados: De 471 aislamientos identificados en diversas muestras clínicas, 317 están asociados a E. coli, y para ambos microorganismos presentaron mayores porcentajes de resistencias al tratamiento antibiótico en áreas no UCI, y evidenciando una resistencia a fármacos como ampicilina y cefalotina, por debajo de 60%, y 75%, respectivamente. Conclusión: Estas bacterias evaluadas, al ser de mayor relevancia clínica, pueden lograr un impacto no deseado por su presencia en áreas no UCI, siendo crítico para E. coli con resistencia a cefalosporinas de tercera y cuarta generación.

Introduction: One of the resistance mechanisms in Gram negative is the production of extended spectrum ß-lactamases (ESBL), capable of conferring resistance to penicillins and cephalosporins. Objective: To determine the prevalence of broad-spectrum ß-lactamases in Escherichia coli and Klebsiella pneumoniae isolates identified in a health institution. Methodology: Results were taken from the clinical laboratory of patients hospitalized for infectious diseases identified in a 4th level hospital in Barranquilla during 2018 associated with E. coli and K. pneumoniae, and their resistance was evaluated. Results: Of 471 isolates identified in various clinical samples, 317 are associated with E. coli, and for both microorganisms they presented higher percentages of resistance to antibiotic treatment in non-ICU areas, and showing resistance to drugs such as ampicillin and cephalothin, below 60%, and 75%, respectively. Conclusion: These evaluated bacteria, being of greater clinical relevance, can achieve an unwanted impact due to their presence in non-ICU areas, being critical for E. coli with resistance to third and fourth generation cephalosporins.

Estimation of the increased risk associated with recurrent events or polyvascular atherosclerotic cardiovascular disease in the United Kingdom.

AIMS: The aims of this study were to re-estimate the international REduction of Atherothrombosis for Continued Health (REACH) risk equation using United Kingdom data and to distinguish different relative hazards for specific atherosclerotic cardiovascular disease event histories. METHODS AND RESULTS: Patients in the UK Clinical Research Practice Datalink (CPRD) were included as of 1 January 2005 if they were 40 years or older, had 2 or more years of prior data, received one or more moderate or high-intensity statin in the previous year, and had a history of myocardial infarction, ischemic stroke, or other atherosclerotic cardiovascular disease. Patients were followed until a composite endpoint of myocardial infarction, ischemic stroke or cardiovascular death, loss to follow-up, or end of observation. We re-estimated the REACH risk equation hazard ratios (HRs) using CPRD data (re-estimated REACH model). Our event history model replaced the REACH vascular bed variables with more specific event histories. There were 60,838 patients with 5.25 years of mean follow-up. In the validation model, HRs were in the same direction, and generally greater than REACH. In the event history model, HRs compared to other atherosclerotic cardiovascular disease alone included: recurrent myocardial infarction (HR 1.19, 95% confidence interval (CI) 1.05-1.34), recurrent ischemic stroke (HR 1.36, 95% CI 1.03-1.80), myocardial infarction and other atherosclerotic cardiovascular disease (HR 1.31, 95% CI 1.23-1.38), ischemic stroke and other atherosclerotic cardiovascular disease (HR 1.40, 95% CI 1.23-1.60), myocardial infarction and ischemic stroke (HR 1.94, 95% CI 1.23-3.04), and myocardial infarction, ischemic stroke and other atherosclerotic cardiovascular disease (HR 1.93, 95% CI 1.47-2.54). CONCLUSION: A detailed cardiovascular event history may be useful for estimating the relative risk of future cardiovascular events.

Clinical impact and room for improvement of intensity and adherence to lipid lowering therapy: Five years of clinical follow-up from 164,565 post-myocardial infarction patients.

BACKGROUND: In patients at risk of cardiovascular (CV) events, the effectiveness of lipid-lowering therapies (LLT) is affected by both intensity and adherence. Our study evaluated the association between LLT intensity (statin and/or ezetimibe) and adherence, and CV events in patients with a history of myocardial infarction (MI) in France. METHODS: Using the French national healthcare database (SNDS), we included patients with a history of MI, an initial LLT prescription in 2011-2013, and a second prescription within one year. LLT intensity was defined using the expected percent reduction in low-density lipoprotein cholesterol; adherence was measured as the proportion of days covered. Cox proportional hazards models were used to assess associations between intensity and/or adherence, and the risk of major adverse CV event (MACE). RESULTS: 164,565 patients were included; mean (SD) age, 66·3 (13·8) years; 73·6% men. Following an MI, only half of patients were treated with high-intensity LLT and approximately 40% of those on LLT remained non-adherent during follow-up (mean (SD) follow-up, 2·6 (1·4) years). Each 10% increase in treatment intensity, adherence, or adherence-adjusted intensity was respectively associated with a 16% (HR 0.84, 95%CI 0.84-0.85), 7% (HR 0.93, 95%CI 0.93-0.94), and 15% (HR 0.85, 95%CI 0.84-0.86) decrease in the risk of MACE. CONCLUSIONS: Among patients with a history of MI, prescriptions of high-intensity LLT were limited and adherence to LLT was low. Higher intensity and/or adherence to statins was associated with a significantly lower risk of MACE, highlighting the importance of compliance with clinical guidelines to improve patient outcomes.

[Ventricular diverticulum in Cantrell´s pentalogy: rare but not isolated entities]. / Divertículo ventricular en pentalogía de Cantrell: entidades infrecuentes, pero no aisladas.

Pentalogy of Cantrell is a rare entity characterized by a combination of alterations, among which the following stand out: defects of the pericardium, heart, diaphragm, lower third of sternum and abdominal wall. On the other hand, congenital cardiac diverticulum is a rare malformation whose presentation is associated with Cantrell's pentalogy in some cases. We present the case of a child with Cantrell's pentalogy who, during follow-up, was diagnosed with left ventricular diverticulum, which required surgical management with a favorable outcome. Addressing these conditions requires the use of cardiovascular images that allow timely decision-making by the treating team.