Clinical Management of Women with Newly Diagnosed Osteoporosis: Data from Everyday Practice in Bulgaria.

INTRODUCTION: The real duration of osteoporosis treatment in clinical practice is still not well described. The primary objective is to estimate the proportion of patients who stayed on treatment during a 4-year follow-up, and the secondary objective is to estimate the proportion of patients who switched treatment and the reasons for switch or discontinuation. METHODS: This was a national retrospective chart review, based on routine clinical data. Data were collected electronically from medical records in 33 representative primary care physicians' sites. Inclusion criteria were women with postmenopausal osteoporosis that have received initial treatment prescription following diagnosis by DXA between January 1, 2012 and December 31, 2014, and at least a 12-month database history after the index date. Exclusion criteria were women receiving treatment for osteoporosis and follow-up at secondary care physicians' sites only. All statistical analyses were performed with the R statistical package. RESULTS: A total of 1206 female patients with newly diagnosed osteoporosis and treatment initiation were followed for 4 years. The majority (88.3%) had no history of previous fractures. Bone mineral density data were available in 70.1%. Endocrinology was the most common specialty among prescribing specialists (40.0%), followed by rheumatology (30.3%). Bisphosphonates (BPs) were the most common initial treatment (72.7%), followed by denosumab (20.1%). Ibandronate (70.2%) and alendronate (24.2%) constituted the majority of all prescribed BPs; 731 patients remained on treatment during the second year (60.6%), 524 during the third year (43.4%) and 403 (33.4%)-at study end (fourth year). In all groups, except that on denosumab, the most common reason for switching to another treatment was presumed lack of effect. The main reasons for treatment discontinuation were financial on the patient's part. CONCLUSIONS: The duration of osteoporosis treatment in real-world clinical practice is far from optimal: < 3-4 years irrespective of fracture risk. Factors other than medical considerations are at play, mainly limitations set by the Health Insurance Fund. The health authorities should be aware of this.

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).

Familial Hypercholesterolaemia in a Bulgarian Population of Patients with Dyslipidaemia and Diabetes: An Observational Study.

INTRODUCTION: Patients with diabetes and familial hypercholesterolaemia (FH) are at very high risk of cardiovascular events, but rates of FH detection are very low in most countries, including Bulgaria. Given the lack of relevant data in the literature, we conducted a retrospective observational study to (1) identify individuals with previously undiagnosed FH among patients being treated at Bulgarian diabetes centres, and (2) gain insight into current management and attainment of low-density lipoprotein cholesterol (LDL-C) goals in such patients. METHODS: From a database of diabetes centres across Bulgaria we retrieved medical records from patients aged ≥ 18 years with type 1/2 diabetes mellitus (T1DM/T2DM) who were being treated with insulin/insulin analogues, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists and/or sodium-glucose co-transporter-2 inhibitors. Patients with FH (Dutch Lipid Clinic Network score ≥ 3) were identified, and their data analyzed (lipid-modifying therapy (LMT), diabetes treatment, cardiovascular events and glycaemic and lipid parameters). RESULTS: A total of 450 diabetic patients with FH (92.0% with T2DM; 52.4% receiving insulin/insulin analogues) were included in the analysis. LMT consisted of statin monotherapy (86% of patients; 18% receiving high-intensity statin monotherapy), statin-based combination therapy (13%) or fenofibrate (< 1%). Median LDL-C was 4.4 mmol/L. Although 30% of patients had a glycated haemoglobin level of ≤ 7%, only one patient (< 1%) achieved the LDL-C target recommended in 2016 European guidelines for very high-risk patients (< 1.8 mmol/L). Previous cardiovascular events were documented in 40% of patients. CONCLUSION: To our knowledge, this is the first study to specifically explore lipid target achievement in diabetic patients with FH. In this preselected Bulgarian population, < 1% of patients achieved the 2016 European guideline-defined LDL-C target. These data highlight the importance of identifying FH in diabetic patients as early as possible so that they can receive appropriate treatment.

Clinical Management of High and Very High Risk Patients with Hyperlipidaemia in Central and Eastern Europe: An Observational Study.

INTRODUCTION: A retrospective/prospective observational study was conducted to explore the current management of hyperlipidaemia in high-risk (HR) and very high risk (VHR) patients in central/eastern Europe and Israel. METHODS: The study enrolled adult patients who were receiving lipid-lowering therapy and attending a specialist (cardiologist/diabetologist/lipidologist) or internist for a routine visit at 57 sites (including academic/specialist/internal medicine centres) across Bulgaria, Croatia, Czech Republic, Israel, Poland, Romania and Slovakia. Data were collected from medical records, for the 12 months before enrolment, with/without ≤ 6 months' additional prospective follow-up. RESULTS: A total of 1244 patients, mean (SD) age 63.3 (11.3) years were included (307 with familial hypercholesterolaemia (FH), 943 secondary prevention patients). Almost all patients (98.1%) were receiving statins (76.7% monotherapy/21.4% combined therapy), with 53.1% receiving high-intensity statin therapy: 127 patients (10.2%) had adverse events attributed to statin intolerance. Mean (SD) low density lipoprotein cholesterol (LDL-C) levels were 3.3 (1.7) mmol/L at the first, and 2.7 (1.3) mmol/L at the last, visit of the retrospective phase of observation, with little change during the prospective phase. Less than one-quarter (23.8%; 95% CI 17.29-31.45%) of HR patients and less than half (42.0%; 39.05-44.98%) of VHR patients achieved their risk-based LDL-C targets of < 2.5 and < 1.8 mmol/L, respectively. Less than 15% of FH patients reached these targets (10.9% (5.6-18.7%) of HR and 12.1% (8.0-17.4%) of VHR patients). The revised 2016 ESC/EAS target for HR patients (2.6 mmol/L) was met by 28.5% (21.44-36.38%) of HR patients overall. Almost one-half of patients (42.1%) experienced one or more cardiovascular events during observation. CONCLUSION: Our findings confirm that, despite widespread statin use, a substantial proportion of patients treated for hyperlipidaemia in central/eastern Europe and Israel, particularly those with FH, do not reach recommended LDL-C targets, thus remaining at risk of cardiovascular events. FUNDING: Amgen (Europe) GmbH.

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.

Baseline Characteristics and Changes in Bone Mineral Density T-Scores of Bulgarian Women with Postmenopausal Osteoporosis Receiving Denosumab in Routine Clinical Practice.

BACKGROUND: Postmenopausal osteoporosis (PMO) is common among women over 50 years of age and is associated with an increased risk of fracture. Bone-targeted agents, such as denosumab, can reduce fracture risk in patients with PMO. OBJECTIVE: The aim was to describe baseline characteristics and changes in bone mineral density (BMD) T-scores among women with PMO receiving denosumab in Bulgaria. METHODS: This multicenter chart review included women with PMO receiving denosumab for ≥1 year in Bulgaria (October 2011-August 2013). Participants were required to have a baseline BMD T-score of ≤-2.5 standard deviations (SDs) at one or more skeletal sites. RESULTS: Overall, 222 women were included. The mean (SD) age at denosumab initiation was 64.2 (8.5) years; 26.6% reported a previous osteoporotic fracture and 6.8% a previous hip fracture. Only half of those reporting a previous fracture (49.2%) had received prior osteoporosis therapy. At baseline, mean (SD) BMD T-scores were lumbar spine -3.2 SD (0.6 SD), total hip -2.3 SD (0.8 SD), and femoral neck -2.7 SD (0.7 SD). After 1 year of denosumab treatment, scores increased significantly at all three sites, reaching -2.7 SD (0.6 SD), -2.1 SD (0.9 SD), and -2.4 SD (0.7 SD), respectively (all p < 0.0001 vs. baseline). No serious adverse drug reactions were identified. CONCLUSION: Denosumab is usually prescribed in women with PMO at high fracture risk. In the patients who were persistent with treatment at 1 year, denosumab was well tolerated and effective at increasing BMD T-scores at several skeletal sites.