New cardiovascular prevention guidelines: How to optimally manage dyslipidaemia and cardiovascular risk in 2021 in patients needing secondary prevention?

Elevated low-density lipoprotein cholesterol (LDL-C) is a principally modifiable cause of atherosclerotic cardiovascular disease; accordingly, recent European and US multisociety dyslipidaemia guidelines emphasise the importance of lowering LDL-C to reduce cardiovascular risk. This review provides perspectives on established and emerging agents that reduce LDL-C to help providers synthesize the abundance of new evidence related to prevention of cardiovascular disease. We provide hypothetical cases of patients with different cardiovascular risk factors and medical histories to illustrate application of current lipid-lowering guidelines in various clinical settings. As a core focus of preventive therapy, both European and US lipid management guidelines emphasise the importance of identifying patients at very high cardiovascular risk and treating to achieve LDL-C levels as low as possible, with European guidelines setting a goal of <1.4 mmol/L (<55 mg/dL) in patients with very high-risk cardiovascular disease. The proprotein convertase subtilisin/kexin type 9 inhibitors are now included in the guidelines and may fulfil an important unmet need for very high-risk patients who are not able to achieve LDL-C goals with conventional agents. The recently approved bempedoic acid and other promising agents under development will add to the armamentarium of lipid-lowering drugs available for clinicians to help patients meet their treatment goals

Hemoglobin Variability Does Not Predict Mortality in European Hemodialysis Patients

Patients with CKD exhibit significant within-patient hemoglobin (Hb) level variability, especially with the use of erythropoiesis stimulating agents (ESAs) and iron. Analyses of dialysis cohorts in the United States produced conflicting results regarding the association of Hb variability with patient outcomes. Here, we determined Hb variability in 5037 European hemodialysis (HD) patients treated over 2 years to identify predictors of high variability and to evaluate its association with all-cause and cardiovascular disease (CVD) mortality. We assessed Hb variability with various methods using SD, residual SD, time-in-target (11.0 to 12.5 g/dl), fluctuation across thresholds, and area under the curve (AUC). Hb variability was significantly greater among incident patients than prevalent patients. Compared with previously described cohorts in the United States, residual SD was similar but fluctuations above target were less frequent. Using logistic regression, age, body mass index, CVD history, dialysis vintage, serum albumin, Hb, angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use, ESA use, dialysis access type, dialysis access change, and hospitalizations were significant predictors of high variability. Multivariable adjusted Cox regression showed that SD, residual SD, time-in-target, and AUC did not predict all-cause or CVD mortality during a median follow-up of 12.4 months (IQR: 7.7 to 17.4). However, patients with consistently low levels of Hb (<11 g/dl) and those who fluctuated between the target range and <11 g/dl had increased risks for death (RR 2.34; 95% CI: 1.24 to 4.41 and RR 1.74; 95% CI: 1.00 to 3.04, respectively). In conclusion, although Hb variability is common in European HD patients, it does not independently predict mortality

An Epidemiological Study of Hemodialysis Patients Based on the European Fresenius Medical Care Hemodialysis Network: Results of the ARO Study

Background/Aims: ARO, an observational study of hemodialysis (HD) patients in Europe, aims to enhance our understanding of patient characteristics and practice patterns to improve patient outcome. Methods: HD patients (n = 8,963) from 134 Fresenius Medical Care facilities treated between 2005 and 2006 were randomly selected from 9 European countries (Czech Republic, France, Hungary, Italy, Poland, Portugal, Spain, Slovak Republic and Slovenia) and Turkey. Information was captured on demographics, comorbidities, medications, laboratory and dialysis parameters, and outcome. Results: Patients were followed for 1.4 8 0.7 years. Wide variation by country was observed for age, sex and diabetes as a cause of chronic kidney disease. Cardiovascular disease was present in 73% of patients. Dialysis parameters were homogeneous across countries. Arteriovenous fistulas were frequently used (73%). More incident patients had hemoglobin ! 11 g/dl than prevalent patients (50 vs. 33%, respectively). Phosphatemia and intact parathyroid hormone were similar between incident and prevalent patients (4.7 8 1.2 mg/dl and 190 vs. 213 ng/l, respectively). Medication use varied widely by country. In total, 5% of patients underwent renal transplantation. Overall death rate was 124/1,000 pa- tient-years. Conclusion: ARO revealed differences in HD practice patterns and patient characteristics in the 10 participating countries. Future ARO studies will fill gaps in the knowledge about the care of European HD patients

The OPTIMA Study: Assessing a New Cinacalcet (Sensipar/Mimpara) Treatment Algorithm for Secondary Hyperparathyroidism

Background and objectives: Cinacalcet, a novel calcimimetic, targets the calcium-sensing receptor to lower parathyroid hormone (PTH), calcium, and phosphorus levels in dialysis patients with secondary hyperparathyroidism (SHPT). This study compared the efficacy of a cinacalcet-based regimen with unrestricted conventional care (vitamin D and phosphate binders) for achieving the stringent National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) targets for dialysis patients

An Epidemiological Study of Hemodialysis Patients Based on the European Fresenius Medical Care Hemodialysis Network:Results of the ARO Study

&lt;i&gt;Background/Aims:&lt;/i&gt; ARO, an observational study of hemodialysis (HD) patients in Europe, aims to enhance our understanding of patient characteristics and practice patterns to improve patient outcome. &lt;i&gt;Methods:&lt;/i&gt; HD patients (n = 8,963) from 134 Fresenius Medical Care facilities treated between 2005 and 2006 were randomly selected from 9 European countries (Czech Republic, France, Hungary, Italy, Poland, Portugal, Spain, Slovak Republic and Slovenia) and Turkey. Information was captured on demographics, comorbidities, medications, laboratory and dialysis parameters, and outcome. &lt;i&gt;Results:&lt;/i&gt; Patients were followed for 1.4 ± 0.7 years. Wide variation by country was observed for age, sex and diabetes as a cause of chronic kidney disease. Cardiovascular disease was present in 73% of patients. Dialysis parameters were homogeneous across countries. Arteriovenous fistulas were frequently used (73%). More incident patients had hemoglobin &lt;11 g/dl than prevalent patients (50 vs. 33%, respectively). Phosphatemia and intact parathyroid hormone were similar between incident and prevalent patients (4.7 ± 1.2 mg/dl and 190 vs. 213 ng/l, respectively). Medication use varied widely by country. In total, 5% of patients underwent renal transplantation. Overall death rate was 124/1,000 patient-years. &lt;i&gt;Conclusion:&lt;/i&gt; ARO revealed differences in HD practice patterns and patient characteristics in the 10 participating countries. Future ARO studies will fill gaps in the knowledge about the care of European HD patients.</jats:p

EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study.

To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination). Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk

EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study

Aims To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. Methods and results An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination). Conclusion Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk