Step-by-step diagnosis and management of the nocebo/drucebo effect in statin-associated muscle symptoms patients: a position paper from the International Lipid Expert Panel (ILEP).

Statin intolerance is a clinical syndrome whereby adverse effects (AEs) associated with statin therapy [most commonly statin-associated muscle symptoms (SAMS)] result in the discontinuation of therapy and consequently increase the risk of adverse cardiovascular outcomes. However, complete statin intolerance occurs in only a small minority of treated patients (estimated prevalence of only 3-5%). Many perceived AEs are misattributed (e.g. physical musculoskeletal injury and inflammatory myopathies), and subjective symptoms occur as a result of the fact that patients expect them to do so when taking medicines (the nocebo/drucebo effect)-what might be truth even for over 50% of all patients with muscle weakness/pain. Clear guidance is necessary to enable the optimal management of plasma in real-world clinical practice in patients who experience subjective AEs. In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step-by-step patient-centred approach to the identification and management of SAMS with a particular focus on strategies to prevent and manage the nocebo/drucebo effect and to improve long-term compliance with lipid-lowering therapy.

Familial Hypercholesterolemia Identification Algorithm in Patients with Acute Cardiovascular Events in A Large Hospital Electronic Database in Bulgaria: A Call for Implementation.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder characterized by a high level of low-density lipoprotein cholesterol (LDL-C) and is an important cause for premature cardiovascular disease. Because of underdiagnoses, an acute event is often the first clinical manifestation of FH. There are limited data on the prevalence and treatment of FH among adults admitted for treatment of acute cardiovascular events in Bulgaria. Our objective was to assess the proportion and management of FH patients from those admitted to hospital for treatment of acute symptomatic acute atherosclerotic cardiovascular events (ASCVD), the achievement of LDL-C targets of European Society of Cardiology/European Atherosclerosis Society guidelines and related public healthcare resources. OBJECTIVE: Digitalized healthcare records for patients admitted for treatment of symptomatic ASCVD acute events between August 2018 and August 2019 were used for the analysis. Five cardiology hospitals provided data for hospitalizations, laboratory tests, and ambulatory follow-ups up to February 2020. Patients' hospital and ambulatory records were linked, and medical histories were extracted via a specifically developed algorithm, and analyzed. Outcomes included the proportion of patients classified as FH as defined by the Dutch Lipid Network Criteria (DLNC), use of lipid-lowering therapy, LDL-C achieved by 1, 3, 6, and 12 months post-index event, and public resources spent on hospital and ambulatory treatment. RESULTS: We reviewed 11,090 hospital records of patients admitted for treatment of acute events in the period August 2018-August 2019 with ICD codes for ASCVD (Supplementary Table S3). FH was identified in 731 (6.6%) patients, with DLNC score ≥ 3, (682 with coronary artery disease, 32 with cerebrovascular disease, and 17 with peripheral artery disease). We did not find the criteria for FH in 5797 patients. The remaining 4562 records were inconclusive due to lack of data in the hospital dossier. Less than half of FH patients (274/731, 37%) were discharged on high-intensity statin therapy prescribed (34/731, 5%) with combination therapy. The vast majority (96.2% with LDL-C ≥ 1.8 mmol/l) had poorly controlled LDL-C during the first year after discharge. Patients with a probable/definite DLNC score ≥ 6 points and those with recurrent events contributed to the higher cost paid both by the healthcare system and the patients themselves. CONCLUSION: These findings reinforce the need for more aggressive lipid-lowering therapy, and underline the efficiency of using an electronic medical records search tool to support physicians in improving early FH diagnosis, aiming to minimize residual and future ASCVD events among FH patients and their family members. Supplementary file1 (MP4 21838 KB).

Management of High and Very High-Risk Subjects with Familial Hypercholesterolemia: Results from an Observational Study in Bulgaria.

BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease (CVD). This retrospective observational study examined the clinical characteristics and management of FH subjects in Bulgaria over a 12-month period. MATERIALS AND METHODS: Twelve cardiology sites participated in this study from May 2015 to May 2016. Eligible subjects had at least two routine low-density lipo-protein cholesterol (LDL C) measurements and a prescription for lipid-lowering therapy (LLT) at the start of the observation period. Mean values for gender, age and cardiovascular (CV) event history at baseline and LDL-C over time were estimated. RESULTS: Of the 220 eligible subjects, 196 fulfilled the criteria for FH diagnosis: 27 definite, 94 probable and 75 possible. Mean age at enrolment was 54.4 years and 64.1% of subjects were male. Mean CV risk classification at baseline was 26.8% high-risk (HR) and 73.2% very high-risk (VHR). Mean LDL-C was 5.6 mmol/L at enrolment and 4.1 mmol/L at last observation visit (12 months). The ESC/EAS Guideline LDL-C targets (applicable at the time of the study) were achieved by 14.5% of HR and 5.0% of VHR subjects. Most subjects (n=219) received statins. One subject was statin intolerant (ezetimibe therapy). Intensive statin treatment (atorvastatin 40-80 mg/daily and rosuvastatin 20-40 mg/daily) was used in 38.6% of individuals during the observation period and 10% of subjects received combination therapy (statin plus ezetimibe or other LLT). CONCLUSIONS: Most subjects with FH do not reach the ESC/EAS defined LDL-C targets. Early identification and physician education may improve FH management.