Quantifying the diagnostic pathway for patients with cognitive impairment: real-world data from Australia.

OBJECTIVES: Rapid diagnosis of dementia is essential to ensure optimum patient care. This study used real-world data to quantify the dementia diagnostic pathway in Australia. DESIGN: A real-world, cross-sectional survey of physicians and patients. SETTING: Clinical practice. PARTICIPANTS: Primary care or specialist physicians managing patients with cognitive impairment (CI). MEASUREMENTS: Descriptive analyses focused on key events in the diagnostic pathway. Regression modeling compared the duration between first consultation and formal diagnosis with various factors. RESULTS: Data for 600 patients were provided by 60 physicians. Mean time from initial symptoms to first consultation was 6.1 ± 4.4 months; 20% of patients had moderate or severe CI at first consultation. Mean time from first consultation to formal diagnosis was 4.0 ± 7.4 months (1.2 ± 3.6 months if not referred to a secondary physician, and 5.3 ± 8.3 months if referred). Time from first consultation to diagnosis was significantly associated with CI severity at first consultation; time was shorter with more severe CI. There was no association of disease severity and referral to a secondary physician; 69.5% of patients were referred, the majority (57.1%) to a geriatrician. The highest proportion of patients were diagnosed by geriatricians (47.4%). Some form of test or scale was used to aid diagnosis in 98.8% of patients. CONCLUSIONS: A substantial number of Australians experience cognitive decline and behavioral changes some time before consulting a physician or being diagnosed with dementia. Increasing public awareness of the importance of early diagnosis is essential to improve the proportion of patients receiving comprehensive support prior to disease progression.

Low-Density Lipoprotein Cholesterol Target Attainment in Patients Surviving an Acute Coronary Syndrome in Thailand: Results From the Dyslipidaemia International Study (DYSIS) II.

BACKGROUND: Patients suffering an acute coronary syndrome (ACS) are at increased risk for future cardiovascular events. Effective management of hyperlipidaemia in such patients is essential. We aimed to document the use of lipid-lowering therapy (LLT) and low-density lipoprotein cholesterol (LDL-C) target achievement in patients hospitalised with an ACS in Thailand. METHODS: The Dyslipidemia International Study (DYSIS) II was a multinational, observational study that enrolled patients over 18 years of age who were hospitalised with an ACS in 2013-2014 and survived until discharge. Patients were analysed according to whether or not they were treated with LLT prior to hospital admission. A lipid profile was carried forward from blood taken within the first 24 hours after admission, and attainment of the LDL-C target of <70 mg/dL (1.8 mmol/L) for very high-risk subjects was reported. Details of LLTs were collected. Lipid levels, LLT use and cardiovascular events since discharge were collected at a follow-up interview 4 months later. RESULTS: A total of 320 ACS patients were enrolled from seven sites across Thailand, 188 (58.8%) of whom were being treated with LLT prior to the acute event. The mean LDL-C levels of the LLT and no LLT patients were 106.2 ± 39.4 mg/dL (2.75 ± 1.02 mmol/L) and 139.8 ± 46.6 mg/dL (3.62 ± 1.21), respectively, with 15.4% and 4.5% having an LDL-C level below 70 mg/dL (1.8 mmol/L). Lipid-lowering therapy consisted mainly of statins, with an atorvastatin-equivalent daily dosage of 17 ± 13 mg/day. At the 4-month follow-up, LDL-C target attainment remained low at 26.7% for the initial LLT group and 24.1% for the no LLT group. Although most patients were being treated with LLT at this point, the dosage was still low (28 ± 16 mg/day) and there was little use of combination therapy. CONCLUSION: In this cohort of Thai ACS patients, LDL-C levels were highly elevated, placing them at extreme risk of recurrent adverse cardiovascular events. Lipid-lowering therapy was widely used after the ACS; however, treatment was rarely optimised. Huge improvements are required in the management of hyperlipidaemia in Thailand.

The Diagnostic Pathway From Cognitive Impairment to Dementia in Japan: Quantification Using Real-World Data.

OBJECTIVE: This study aimed to quantify the diagnostic pathway from cognitive impairment (CI) to dementia in Japan. METHODS: This was a real-world, cross-sectional survey of patients with CI and their physicians. RESULTS: Data for 1107 patients were provided by 106 physicians. Mean time from initial symptoms to the first consultation was 7.4±6.9 months; 42% of patients had moderate/severe CI at first consultation. Mean time from the first consultation to formal diagnosis was 2.9±11.0 months (1.9±8.8 mo if not referred to a secondary physician, and 5.1±14.6 mo if referred). Time from the first consultation to diagnosis was shorter with more severe CI at first consultation (P=0.0072). The highest proportion of patients were diagnosed by neurologists (45.8%). Tests or scales were used to aid diagnosis in 81.2% of patients. There was no association of disease severity and referral to a secondary physician; 30.9% of patients were referred, the majority (57.7%) to a neurologist. CONCLUSIONS: A substantial proportion of patients with dementia in Japan experience CI for some time before consulting a physician. Government policy to increase public understanding and awareness of dementia, and a proposed dementia screening system, should increase the proportion of individuals consulting physicians before disease progression.

Body mass index impacts the choice of lipid-lowering treatment with no correlation to blood cholesterol - Findings from 52 916 patients in the Dyslipidemia International Study (DYSIS).

A high body mass index (BMI) is associated with increased cardiovascular risk. We sought to identify whether BMI influences the choice of lipid-lowering treatment in a large, real-world cohort of 52 916 patients treated with statins. The Dyslipidemia International Study (DYSIS) is a cross-sectional, observational, multicentre study in statin-treated patients ≥45 years of age from 30 countries; 1.1% were underweight (BMI < 18.5 kg/m2 ), 33.1% had normal weight (BMI 18.5-24.9 kg/m2 ), 41.5% were overweight (BMI 25-29.9 kg/m2 ), 17.1% had class I obesity (BMI 30.0-34.9 kg/m2 ), 5.0% had class II obesity (BMI 35-39.9 kg/m2 ), and 2.1% had class III obesity (≥40 kg/m2 ). BMI correlated with high-density lipoprotein cholesterol (HDL-C) and triglycerides (Spearman's ρ: -0.147 and 0.170, respectively; P < 0.0001 for both); however, there was no correlation with low-density lipoprotein cholesterol (LDL-C; ρ: 0.003; P = 0.51). Statin intensity increased with increasing BMI (ρ: 0.13; P < 0.001), an association that held after adjustment for comorbidities (OR: 2.4; 95% CI: 2.0-3.0) on BMI ≥ 30 kg/m2 for atorvastatin equivalent ≥40 mg/d.

Prevalence of mixed dyslipidemia among Australian patients undergoing lipid-modifying therapy.

BACKGROUND: Few studies have assessed the prevalence of mixed dyslipidemia (MD) and the effectiveness of lipid-modifying therapy (LMT) for the treatment of abnormal levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) in Australian clinical practice. OBJECTIVE: To estimate the prevalence of MD in Australian patients undergoing LMT. METHODS: Patients 35 years of age and older undergoing LMT for ≥1 year were enrolled from nine general practice and cardiologist/endocrinologist outpatient clinics in Australia between April 2007 and May 2008. Lipid levels, including LDL-C, HDL-C and TG levels, were prospectively collected at the enrollment date and from patient records one year before LMT was initiated. Normal lipid levels were assessed according to Australian guidelines. Multivariate logistic regression was used to evaluate predictors of normal lipid level attainment. RESULTS: Of 297 patients (mean age 60.1 years; 43% male), the prevalence of MD before LMT was 61%; 93% of patients had elevated LDL-C levels, 17% had low HDL-C levels and 62% had elevated TG levels. Following LMT (98.3% statins), 31% of patients had MD. The prevalence of elevated LDL-C levels, low HDL-C levels and elevated TG levels were 44%, 21% and 42%, respectively. Baseline lipid levels were significant predictors of attainment of normal LDL-C levels (OR 0.42 [95% CI 0.27 to 0.63]) and TG levels (OR 0.26 [95% CI 0.16 to 0.45]). CONCLUSION: Among Australian patients primarily treated with statins, nearly one-third had MD despite LMT. LMT considerably improved LDL-C goal attainment; however, a large proportion of patients did not achieve normal HDL-C and TG levels. Patients may benefit from a more comprehensive approach to lipid management that treats all three lipid risk factors, as suggested in clinical guidelines.

Quality of Life and Caregiver Burden of Alzheimer's Disease Among Community Dwelling Patients in Europe: Variation by Disease Severity and Progression.

BACKGROUND: Alzheimer's disease (AD) is a significant burden on patients and caregivers. How this burden increases as disease progresses has not been well researched. OBJECTIVE: To assess the association of caregiver burden and quality of life with Alzheimer's disease severity and disease progression in community-dwelling patients in Germany, Spain, and the UK. METHODS: This was a prospective observational longitudinal study of mild-to-moderate AD patients (assessed by Mini-Mental State Examination, MMSE), and their caregivers. The humanistic burden was assessed using these instruments: [Rapid Assessment of Physical Activity (RAPA), EuroQoL-5-Dimension Level (EQ-5D-5L)] and caregiver-reported [Dependence Scale (DS), EQ-5D-5L, Zarit Burden Interview (ZBI)]. Caregiver-reported healthcare resource use was assessed using the Resource Use in Dementia (RUD) and ad-hoc questions. RESULTS: Of 616 patients recruited, 338 and 99 were followed-up at 12 and 18 months, respectively. The caregiver-reported EQ-5D-5L scores of patients' health-related quality of life (HRQoL) showed a negative trend over time (baseline: 0.76; 18 months: 0.67) while patient-reported HRQoL remained at 0.85. DS scores tended to worsen. Disease progression was an independent predictor of HRQoL and increased dependence.Mean ZBI score increased over time reflecting an increase in caregiver burden; MMSE being an independent predictor for caregiver burden. Patient resource utilization and caregiver time for caregiving tended to increase over time. CONCLUSION: We found significant association between disease progression and caregiver and patient burden. Independently, both disease-specific outcomes and disease burden measures increased over time, but as disease progresses, we also found incremental burden associated with it.

Assessing the Progression of Alzheimer's Disease in Real-World Settings in Three European Countries.

BACKGROUND: There exists considerable variation in disease progression rates among patients with Alzheimer's disease (AD). OBJECTIVE: The primary objective of this observational study is to assess the progression of AD by characterizing cognitive, functional, and behavioral changes during the follow-up period between 6 and 24 months. METHODS: A longitudinal prospective study with community-dwelling patients with an established clinical diagnosis of AD of mild to moderate severity was conducted in Germany, Spain and the UK. A sample of 616 patients from 69 sites was included. RESULTS: Patients had a mean of 1.9 years (SD = 1.9) since AD diagnosis at study inclusion. Cognitive symptoms were reported to have first occurred a mean of 1.1 years (SD = 1.7) prior to AD diagnosis and 1.4 (SD = 1.8) years prior to AD treatment. Patients initially diagnosed with mild and moderate AD spent a median (95%CI) of 3.7 (2.8; 4.4) and 11.1 (6.1, 'not reached') years until progression to moderate and severe AD, respectively, according to the Mini-Mental State Examination (MMSE) scores. A mixed model developed for cognitive, functional, and neuropsychiatric scores, obtained from study patients at baseline and during follow-up period, showed progressive deterioration of AD patients over time. CONCLUSION: The study showed a deterioration of cognitive, functional, and neuropsychiatric functions during the follow-up period. Cognitive deterioration was slightly faster in patients with moderate AD compared to mild AD. The duration of moderate AD can be overestimated due to the use of retrospective data, lack of availability of MMSE scores in clinical charts and exclusion of patients at time of institutionalization.

The effects of isolated versus multiple lipid disorders on resource utilization among metabolic syndrome patients with lipid abnormalities despite Lipid-modifying treatment.

OBJECTIVE: The aim of this study was to compare resource utilization among metabolic syndrome (MetS) patients with multiple (≥ 2) lipid disorders (MLD) versus isolated (any 1) lipid disorder (ILD). METHODS: Data for MetS patients on lipid-modifying therapy (LMT) were collected from the 2006 Adelphi Metabolic Syndrome Disease Specific Programme(©) cross-sectional study of patients from 5 European countries. The presence of MetS and lipid disorders, including elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and low high-density lipoprotein (HDL-C), were based on the National Cholesterol Education Program definitions. Analyses compared primary care physician (PCP) and specialist visits over the past 6 months among ILD versus MLD patients. RESULTS: Among 4,836 MetS patients, 2,843 had ≥ 1 lipid disorders and were on LMT. Controlling for other risk factors, MLD patients had significantly higher physician visits than those with ILD (p = 0.009), but hospitalizations were not significantly different. Patients experiencing all 3 lipid disorders had significantly more endocrinologist visits (p = 0.002) as compared with ILD patients, while patients with elevated LDL-C and abnormal HDL-C and/or TG compared with isolated elevated LDL-C had significantly more PCP (p = 0.001) and cardiologist visits (p < 0.001). CONCLUSION: Among MetS patients on LMT, presence of MLD resulted in significantly higher PCP and specialist visits compared with ILD.

Prevalence of lipid abnormalities before and after introduction of lipid modifying therapy among Swedish patients with dyslipidemia (PRIMULA).

BACKGROUND: Data on the prevalence of dyslipidemia and attainment of goal/normal lipid levels in a Swedish population are scarce. The objective of this study is to estimate the prevalence of dyslipidemia and attainment of goal/normal lipid levels in patients treated with lipid modifying therapy (LMT). METHODS: This longitudinal retrospective observational study covers time periods before and after treatment. Data were collected from 1994-2007 electronic patient records in public primary healthcare centers in Uppsala County, Sweden. Patients were included if they had been treated with LMT and had at least one lipid abnormality indicating dyslipidemia and if complete lipid profile data were available. Thresholds levels for lipids were defined as per Swedish guidelines. RESULTS: Among 5,424 patients included, at baseline, the prevalence of dyslipidemia (≥1 lipid abnormality) was by definition 100%, while this figure was 82% at follow-up. At baseline, 60% had elevated low-density lipoprotein (LDL-C) combined with low high-density lipoprotein (HDL-C) and/or elevated triglycerides (TG s), corresponding figure at follow-up was 36%. Low HDL-C and/or elevated TGs at follow-up remained at 69% for patients with type 2 diabetes mellitus (T2DM), 50% among patients with coronary heart disease (CHD) and 66% among patients with 10 year CHD risk >20%. Of the total sample, 40% attained goal levels of LDL-C and 18% attained goal/normal levels on all three lipid parameters. CONCLUSIONS: Focusing therapy on LDL-C reduction allows 40% of patients to achieve LDL-C goal and helps reducing triglyceride levels. Almost 60% of patients experience persistent HDL-C and/or triglyceride abnormality independently of LDL-C levels and could be candidates for additional treatments.

Multi-National, Cross-Sectional Survey of Healthcare Resource Utilization in Patients with All Stages of Cognitive Impairment, Analyzed by Disease Severity, Country, and Geographical Region.

BACKGROUND: Alzheimer's disease (AD) is one of the most disabling conditions worldwide and the disease burden increases with the aging global population. There are only a few prospective studies using real-world data to support effective healthcare resource utilization (HCRU) in AD. OBJECTIVE: To confirm the association between HCRU and AD severity in a real-world population, including patients with all cognitive impairment (CI) severities. METHODS: Data were drawn from a multi-national, cross-sectional survey of physicians and their consulted patients with all stages (very mild, mild, moderate, and severe) of CI including AD conducted in France, Germany, Italy, Spain, UK, US, and Canada. Elements of HCRU including medical consultations, professional caregiver hours, hospitalization, and institutionalization were compared between CI severity subgroups, and by country and region. RESULTS: 6,143 CI patients were included with very mild (n = 659), mild (n = 2,473), moderate (n = 2,603), and severe (n = 408) dementia. HCRU increased with increasing CI severity (p < 0.001) for the majority of elements measured. Further analyses of overall and regional populations also confirmed significant increases in most HCRU elements with increasing disease severity. The general trend toward increased HCRU with increased CI severity was also seen in individual countries. Individual country data appeared to indicate that earlier intervention decreased hospitalizations and full-time institutionalization at the later (more severe) disease stages. CONCLUSION: Our findings confirmed that HCRU increases with increasing CI severity. Effective intervention in early disease could therefore reduce or delay incurring greater HCRU costs associated with more severe disease. Further studies are needed to confirm this hypothesis.

Lipid-lowering treatment and low-density lipoprotein cholesterol target achievement in patients with type 2 diabetes and acute coronary syndrome.

BACKGROUND: Patients with type 2 diabetes mellitus characteristically display an atherogenic lipid profile with high triglyceride concentrations, low high-density lipoprotein cholesterol (HDL-C) concentrations and low-density lipoprotein cholesterol (LDL-C) concentrations not always elevated. It is unclear if patients with diabetes who present with an acute coronary syndrome (ACS) receive different or more-potent lipid-lowering therapy (LLT). AIMS: To investigate lipid abnormalities in patients with and without type 2 diabetes hospitalised for an ACS, and use of LLT before admission and 4 months after the event. METHODS: Patients were included in the observational DYSIS II study if they were hospitalised for an ACS and had a full lipid profile. RESULTS: Of 3803 patients, diabetes was documented in 1344 (54.7%). Compared to patients without diabetes, those with diabetes had a lower mean LDL-C (101.2 vs. 112.0mg/dL; 2.6 vs. 2.9mmol/L; P<0.0001), with a greater proportion attaining concentrations<70mg/dL (1.8mmol/L) (23.9% vs. 16.0%; P<0.0001) and<55mg/dL (1.4mmol/L) (11.3% vs. 7.3%; P<0.0001), a higher mean triglyceride concentration (139.0 vs. 121.0mg/dL; 1.6 vs. 1.4mmol/L; P<0.0001) and a lower HDL-C concentration. LLT was more commonly given to patients with diabetes (77.5% vs. 58.8%; P<0.0001); there were no differences in types of therapy prescribed. Four months after hospitalisation, most patients from both groups were being treated with LLT (predominantly statin monotherapy). CONCLUSIONS: Despite the different lipid profiles, the type of LLT prescribed did not vary depending on the presence or absence of type 2 diabetes. There was no difference in LLT in patients with and without diabetes at 4-month follow-up, except for fibrates, which were used in 2% of patients with and 1% of patients without diabetes. Statin monotherapy of intermediate potency was the predominant treatment in both groups.

Patients' experiences of niacin-induced flushing in clinical practice: a structured telephone interview.

BACKGROUND: Niacin is highly effective at raising high-density lipoprotein cholesterol but remains underused because of the adverse event of flushing. OBJECTIVE: The objective of this study was to determine the incidence and severity of niacin-induced flushing and their relationship to niacin discontinuation and skipping or delaying niacin doses in clinical practice. The use of aspirin to avoid niacin-induced flushing was also assessed. METHODS: Structured telephone interviews were performed with patients identified from administrative claims data as having newly initiated niacin. The main outcome measures were rate and severity of flushing, association between flushing and niacin discontinuation, and rate of prophylactic aspirin use to avoid flushing. Flushing was evaluated on a scale of none, mild, moderate, severe, and extreme. RESULTS: Telephone interviews were conducted with 500 patients who had newly initiated niacin. The patients interviewed were predominantly white men with at least some college education and a mean (SD) age of 55.0 (10.9) years. The mean (SD) time between therapy initiation and interview was 9.3 (3.3) months. At the time of the interview, 27.2% of respondents reported having discontinued niacin ("discontinuers"; n = 136), with a mean duration of niacin use of 4.3 months, and 72.8% continued taking niacin ("continuers"; n = 364). Approximately 91.2% (124/136) of niacin discontinuers and 82.1% (299/364) of continues reported experiencing flushing symptoms (P = 0.013), and 54.4% of discontinuers versus 20.9% of continuers experienced severe or extreme flushing (P < 0.001). Significantly more discontinuers (79.4%) than continuers (58.0%) reported that the greatest degree of flushing they could tolerate was "mild" or "moderate" (P < 0.001). Multivariate logistic regression indicated that flushing symptom severity was a strong predictor of discontinuation as compared with no flushing symptoms (severe: odds ratio [OR], 3.19; 95% CI, 1.43-7.15; extreme: OR, 11.29; 95% CI, 4.20-30.39). Similar percentages of discontinuers and continuers reported both receiving a physician's advice to take prophylactic aspirin (42.0% vs 49.5%, respectively; P = NS) and actually taking aspirin regardless of what their physicians advised (36.0% vs 43.7%; P = NS). CONCLUSIONS: Severe or extreme symptoms of flushing, which occurred in about one third of patients newly treated with niacin, were associated with discontinuation of this otherwise highly effective therapy. Less than half of patients reported being advised by their physician to take prophylactic aspirin or took aspirin regardless of their physician's recommendation to avoid niacin-induced flushing symptoms.

Physician Perceptions about the Barriers to Prompt Diagnosis of Mild Cognitive Impairment and Alzheimer's Disease.

Prior studies have identified numerous barriers to the prompt diagnosis of patients with suspected Alzheimer's disease (AD). The aim of the study was to evaluate physician's perceptions of the importance of previously identified barriers to diagnosis, but with a specific focus on the presentation of mild cognitive impairment (MCI), which may be indicative of neurodegenerative disorders such as AD. A second aim was to evaluate how the perspective of primary care physicians (PCPs) may differ from that of specialists. A cross-sectional online survey of PCPs and specialists who routinely manage patients with complaints of age-related cognitive impairment was conducted. Participants were asked to identify barriers to prompt diagnosis from prespecified lists of known diagnostic challenges categorized into 4 domains: patient-related, physician-related, setting-related, and those relating to the clinical profile of AD. Physicians report a range of barriers when attempting to diagnose MCI and AD. Major themes included patients seeing cognitive decline as a normal part of aging and not disclosing symptoms, long waiting lists, and a lack of treatment options and definitive biomarker tests. Generally, PCPs and specialists showed broad agreement; however, PCPs were more likely to identify burdens on the healthcare system, such as long waiting lists and inadequate time to evaluate patients. Substantial barriers continue to hinder early diagnosis of MCI and AD. There are numerous areas where improvements might be made but the implementation of potential interventions will likely be associated with financial strain for many healthcare systems.

Physician Practice Patterns Associated with Diagnostic Evaluation of Patients with Suspected Mild Cognitive Impairment and Alzheimer's Disease.

The diagnostic process for patients presenting with cognitive decline and suspected dementia is complex. Physicians face challenges distinguishing between normal aging, mild cognitive impairment, Alzheimer's disease, and other dementias. Although there is some evidence for improving attitudes towards the importance of prompt diagnosis, there is limited information describing how physicians approach this diagnostic challenge in practice. This was explored in the present study. Across-sectional survey of primary care and specialist physicians, in 5 European countries, Canada, and the United States, was conducted. Participants were asked about their use of cognitive screening tools and diagnostic technologies, as well as the rationales and barriers for use. In total, 1365 physicians participated in the survey, 63% of whom were specialists. Most physicians stated they use objective cognitive tools to aid the early detection of suspected mild cognitive impairment or Alzheimer's disease in patients. The Mini-Mental State Examination was the most common tool used for initial screening; respondents cited speed and ease of use but noted its lack of specificity. Cerebrospinal fluid biomarker and amyloid positron emission tomography tests, respectively, had been used by only 26% and 32% of physicians in the preceding 6 months, although patterns of use varied across countries. The most commonly cited reasons for not ordering such tests were invasiveness (for cerebrospinal fluid biomarker testing) and cost (for amyloid positron emission tomography imaging). Data reported by physicians reveal differences in the approaches to the diagnostics process in Alzheimer's. A higher proportion of primary care physicians in the United States are routinely incorporating cognitive assessment tools into annual visits, but this is due to country differences in clinical practice. The value of screening tools and regular use could be discussed further with physicians; however, lack of specificity associated with cognitive tools and the investment required from patients and the healthcare system are limiting factors.

Ezetimibe in high-risk, previously treated statin patients: a systematic review and network meta-analysis of lipid efficacy.

PURPOSE: While statins are used as first-line treatments for high-risk patients with hypercholesterolemia, statin monotherapy is often insufficient to achieve target low-density lipoprotein cholesterol (LDL-C) levels. Second-line treatment options include up-titration of statin dose, switching to a more potent statin, or combination therapy, e.g., with ezetimibe. The aim of this study was to evaluate the efficacy of adding ezetimibe to simvastatin, atorvastatin, or rosuvastatin monotherapy versus doubling the dosage or switching to a higher-potency statin in a population of patients with hypocholesterolemia at high risk of cardiovascular disease (CVD) and who had been previously treated with a statin. METHODS: A systematic literature search was performed and evidence bases were established for populations of atorvastatin-, simvastatin-, and rosuvastatin-experienced patients using eligible randomized controlled trials (RCTs). Based on the available data, we constructed networks of evidence and conducted a Bayesian network meta-analysis (NMA) within each statin population. The primary outcome of interest was percent change from baseline in LDL-C. Changes in total cholesterol were explored as a secondary outcome. FINDINGS: Across all patient populations, 35 RCTs were identified and included in the evidence base. Among patients on simvastatin therapy, the addition of ezetimibe resulted in a mean difference (MD) in LDL-C of - 13.62% (95% CrI - 19.99, - 6.91; see table below) compared to doubling the starting dose of simvastatin. In the population of patients on atorvastatin therapy, the addition of ezetimibe resulted in an MD in LDL-C of - 14.71% (95% CrI - 16.46, - 12.95) compared to doubling the starting dose of atorvastatin. The addition of ezetimibe to rosuvastatin resulted in an MD in LDL-C of - 14.96% (95% CrI - 17.79, - 12.11), compared to doubling the starting rosuvastatin dose. Similar trends were observed for changes in total cholesterol. IMPLICATIONS: Given the available data, the addition of ezetimibe to ongoing simvastatin, atorvastatin, or rosuvastatin monotherapy offers greater reduction in LDL-C among patients at high risk of CVD compared to doubling the initial statin dose.

Cholesterol goal achievement and lipid-lowering therapy in patients with stable or acute coronary heart disease in Singapore: results from the Dyslipidemia International Study II.

INTRODUCTION: Dyslipidaemia is a major risk factor for coronary heart disease (CHD). There is a lack of data on the extent of lipid abnormalities and lipid-lowering therapy (LLT) in Singapore. METHODS: The Dyslipidemia International Study (DYSIS) II was a multinational observational study of patients with stable CHD and hospitalised patients with an acute coronary syndrome (ACS). A full lipid profile and use of LLT were documented at baseline, and for the ACS cohort, at four months post-hospitalisation. RESULTS: 325 patients were recruited from four sites in Singapore; 199 had stable CHD and 126 were hospitalised with an ACS. At baseline, 96.5% of the CHD cohort and 66.4% of the ACS cohort were being treated with LLT. In both cohorts, low-density lipoprotein cholesterol (LDL-C) levels were lower for the treated than the non-treated patients; accordingly, a higher proportion of patients met the LDL-C goal of < 70 mg/dL (CHD: 28.1% vs. 0%, p = 0.10; ACS: 20.2% vs. 0%, p < 0.01). By the four-month follow-up, a higher proportion of the ACS patients that were originally not treated with LLT had met the LDL-C goal (from 0% to 54.5%), correlating with the increased use of medication. However, there was negligible improvement in the patients who were treated prior to the ACS. CONCLUSION: Dyslipidaemia is a significant concern in Singapore, with few patients with stable or acute CHD meeting the recommended European Society of Cardiology/European Atherosclerosis Society goal. LLT was widely used but not optimised, indicating considerable scope for improved management of these very-high-risk patients.

Attainment of cholesterol target values in Greece: results from the Dyslipidemia International Study II.

INTRODUCTION: Current European guidelines recommend treatment with lipid-lowering therapy (LLT) to a low-density lipoprotein cholesterol (LDL-C) target of < 70 mg/dl for patients at very high risk. LDL-C target attainment and use of LLTs in these patients in Greece is not known. MATERIAL AND METHODS: The Dyslipidemia International Study (DYSIS) II was a multicenter observational study. The coronary heart disease (CHD) cohort was divided into two groups based on treatment status (on LLT for ≥ 3 months or not on LLT). The acute coronary syndrome (ACS) cohort was evaluated at the time of admission and again 120 ±15 days after admission. RESULTS: In the CHD cohort (n = 499), 457 (91.6%) patients were on LLT. The LDL-C target value was attained by 26.5% of LLT users. Statin monotherapy was used by 77.5% of treated patients, with a mean ± SD atorvastatin dose equivalent of 24 ±16 mg/day. In the ACS cohort (n = 200), 159 (79.5%) patients were on LLT at admission. Mean ± SD LDL-C levels were 108 ±40 mg/dl at admission and 86 ±25 mg/dl at follow-up. LDL-C target value attainment rates were 16.2% at admission and 25.0% at follow-up. At admission, statin monotherapy was used by 86.8% of treated patients. The mean ± SD atorvastatin dose equivalent increased from 20 ±14 mg/day at admission to 29 ±15 mg/day at follow-up. The statin dose was associated with higher odds of LDL-C target value attainment (OR = 1.05, 95% CI: 1.02-1.08). CONCLUSIONS: The LDL-C target attainment by very high risk patients in Greece is suboptimal. Increasing the statin dose or combining it with non-statins may improve target value attainment.

Prevalence of Lipid Abnormalities and Cholesterol Target Value Attainment in Patients with Stable and Acute Coronary Heart Disease in the United Arab Emirates.

BACKGROUND: Careful management of lipid abnormalities in patients with coronary heart disease (CHD) or an acute coronary syndrome (ACS) can reduce the risk of recurrent cardiovascular events. The extent of hyperlipidemia in these very high-risk patients in the United Arab Emirates (UAE), along with the treatment strategies employed, is not clear. METHODS: The Dyslipidemia International Study II was a multinational observational analysis carried out from 2012 to 2014. Patients were enrolled if they had either stable CHD or an ACS. Patient characteristics, lipid levels, and use of lipid-lowering therapy (LLT) were recorded at enrollment. For the ACS patients, the LLT used during the 4 months' follow-up period was documented, as were any cardiovascular events. RESULTS: A total of 416 patients were recruited from two centers in the UAE, 216 with stable CHD and 200 hospitalized with an ACS. Comorbidities and cardiovascular risk factors were extremely common. A low-density lipoprotein cholesterol level of <70 mg/dl, recommended for patients at very high cardiovascular risk, was attained by 39.3% of the LLT-treated CHD patients and 33.3% of the LLT-treated ACS patients at enrollment. The mean atorvastatin-equivalent daily statin dose was 29 ± 15 mg for the CHD patients, with 13.7% additionally using ezetimibe. For the ACS patients, the daily dosage was 23 ± 13 mg at admission, rising to 39 ± 12 mg by the end of the 4-month follow-up. The use of nonstatin agents was extremely low in this group. CONCLUSIONS: Despite LLT being widely used, hyperlipidemia was found to be prevalent in ACS and CHD patients in the UAE. Treatment strategies need to be significantly improved to reduce the rate of cardiovascular events in these very high-risk patients.

Frequency and predictors of cholesterol target attainment in patients with stable coronary heart disease in Belgium: results from the Dyslipidemia International Study II (DYSIS II CHD).

Objectives: To document the frequency and predictors of low-density lipoprotein cholesterol (LDL-C) target value attainment among patients with coronary heart disease (CHD) in Belgium. Methods: The second Dyslipidemia International Study (DYSIS II) was an observational study of the prevalence of dyslipidemias and lipid target value attainment. Patients in this analysis were aged ≥ 18, had documented CHD, and had a full lipid profile. Use of lipid-lowering therapy (LLT), lipid profile, and LDL-C target value attainment (< 70 mg/dL) were assessed cross-sectionally at the enrollment visit. The distribution of LLTs was assessed among treated patients. Multivariate logistic regression was used to identify variables predictive of LDL-C target value attainment in treated patients. Results: We identified 409 patients with CHD in Belgium, 387 (94.6%) of whom were on LLT at the time of the lipid profile. Among treated patients, the rate of LDL-C target value attainment was 40.6%, and statin monotherapy was the most commonly used LLT (79.3%). Among users of statin monotherapy or combination therapy, simvastatin was the most commonly used treatment (41.6% of patients). Diabetes was associated with higher odds of LDL-C target value attainment (OR 2.29, 95% CI 1.33-3.93), and female gender was associated with lower odds (OR 0.48, 95% CI 0.24-0.97). Conclusion: Rates of LDL-C target value attainment are low in patients with CHD in Belgium. Intensifying statin therapy or combining it with non-statins is essential in Belgian patients for optimal LDL-C reduction.

Dyslipidemia and Rate of Under-Target Low-Density Lipoprotein-Cholesterol in Patients with Coronary Artery Disease in Korea.

OBJECTIVE: The aim of this study was to evaluate under target rates of low-density lipoprotein-cholesterol (LDL-C) in Korean patients with stable coronary artery disease (CAD) or an acute coronary syndrome (ACS) in real world practice. METHODS: Dyslipidemia International Study II was an international observational study of patients with stable CAD or an ACS. Lipid profiles and use of lipid-lowering therapy (LLT) were documented at enrollment, and for the ACS cohort, 4 months follow-up was recommended. Rates of under target LDL-C as per European guidelines, were evaluated, and multivariate regression was performed to identify predictive factors of patients presenting under the target. RESULTS: A total of 808 patients were enrolled in Korea, 500 with stable CAD and 308 with ACS. Of these, 90.6% and 52.6% were being treated with LLT, respectively. In the stable CAD group, 40.0% were under target LDL-C, while in ACS group, the rate was 23.7%. A higher statin dose was independently associated with under target LDL-C in both groups (OR, 1.03; p=0.046 [stable CAD] and OR, 1.05; p=0.01 [ACS]). The mean statin dosage (atorvastatin equivalent) was 17 mg/day. In the 79 ACS patients who underwent the follow-up examination, the LDL-C under target rate rose to 59.5%. CONCLUSION: Only a minority of patients with stable CAD or ACS were under their target LDL-C level at enrollment. The statin dose was not sufficient in the majority of patients. These results indicate a considerable LLT gap in Korean patients with established CAD.