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.

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.

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.

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.

Non-professional caregiver burden is associated with the severity of patients' cognitive impairment.

BACKGROUND/OBJECTIVES: To analyse the relationship between caregiver burden and severity of patients' cognitive impairment. DESIGN: Data were drawn from the cross-sectional 2015/2016 Adelphi Real World Dementia Disease-Specific Programme. SETTING: This research was multi-national and studied physicians and their consulting patients with cognitive impairment. PARTICIPANTS: 1,201 caregivers completed self-assessment forms. MEASUREMENTS: Validated instruments of caregiver wellbeing and burden (EQ-5D-3L questionnaire, EQ-VAS, Zarit Burden Interview, and Work Productivity and Activity Impairment questionnaire) and number of caregiver hours were analysed by severity of patients' cognitive impairment, categorised according to the Mini-Mental State Examination. Data were analysed using Spearman's rank correlation coefficients and ordinary least squares regression models, to compare outcomes between caregivers of patients with prodromal, mild, moderate, and severe dementia. RESULTS: The majority of caregivers were female (69.1%), lived with the patient they cared for (75.8%), and only approximately one third (28.3%) were in part- or full-time employment. There were statistically significant (p<0.001) increases in caregiver time (36.9 versus 108.6 hours per week for prodromal versus severe dementia, respectively) and measures of caregiver burden and health status (EQ-5D-3L, EQ-VAS, and Zarit Burden Interview) and increases in measures of work productivity and activity impairment with increasing severity of patients' disease. CONCLUSION: This study of real-world data confirmed an association between increased caregiver burden and severity of patients' cognitive impairment by analysis of a wide range of validated measures of caregiver burden. These findings suggest that maintaining patients in the earliest stages of their disease for as long as possible may potentially help to protect caregiver wellbeing, although further research is required to confirm this hypothesis.

Real-World, Multinational, Retrospective Observational Survey of the ADAS-Cog and Associations with Healthcare Resource Utilization in Patients with Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most costly conditions, both economically and regarding patient disability and dependency. The huge costs coupled with the predicted increase in prevalence worldwide are likely to challenge healthcare systems in the future. The classic version of the Alzheimer's Disease Assessment Scale-Cognition subscale (ADAS-Cog) is generally seen as the current gold standard primary outcome measure of cognitive symptom progression in dementia clinical trials. OBJECTIVE: This study evaluated the relationship between ADAS-Cog scores as a measure of clinical progression and the healthcare resource utilization (HCRU)-measured burden of cognitive impairment in patients with mild cognitive impairment, AD, or suspected AD in the real world. METHODS: A retrospective observational survey of physicians and their consulting patients with multiple ADAS-Cog scores. Regression models were constructed for HCRU variables (e.g., consultations, hospitalizations, caregiving requirements) with ADAS-Cog rate of change, baseline ADAS-Cog, and their interaction included as exposure variables. RESULTS: 651 patient records were completed by 154 physicians. Approximately 70% of patients had mild to moderate dementia. In 56.7% of patients, clinical progression was maintained/stable from baseline. Mean change in ADAS-Cog (adjusted to 12 months) was 2.8 points and change scores increased with increasing dementia severity. Most HCRU variables increased significantly (p < 0.05; joint test) with increasing ADAS-Cog scores (indexing clinical deterioration). CONCLUSION: The results suggest that further understanding the relationship between HCRU and ADAS-Cog changes in real-world clinical practice could potentially provide a baseline upon which the success of disease-modifying, as well as newer symptomatic, dementia therapies can be judged.

Use of guideline-recommended management in established coronary heart disease in the observational DYSIS II study.

BACKGROUND: Guidelines recommend lifestyle modification and medications to control risk factors in coronary heart disease (CHD). Using data from the observational DYSIS II study, we sought to evaluate the use of guideline-recommended treatments at discharge for acute coronary syndromes (ACS) or in the chronic phase for CHD, and participation in rehabilitation/secondary prevention programs. METHODS AND RESULTS: Between 2013 and 2014, 10,661 patients (3867 with ACS, 6794 with stable CHD) were enrolled in 332 primary and secondary care centers in 18 countries (Asia, Europe, Middle East). Patients with incident ACS were younger and more likely to be smokers than patients with recurrent ACS or stable CHD (both p < 0.0001). Sedentary lifestyle was common (44.4% of ACS patients; 44.2% of stable CHD patients); 22.8% of ACS patients and 24.3% of stable CHD patients were obese. Prevalence of low high-density lipoprotein cholesterol (<40 mg/dL in men/50 mg/dL in women) was 46.9% in chronic CHD and 55.0% in ACS. Rates of secondary prevention medications were lower among CHD versus ACS (all p < 0.0001): antiplatelet 94.3% vs 98.0%, beta-blocker 72.0% vs 80.0%, lipid-lowering therapy 94.7 vs 97.5%, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers 69.4% vs 73.7%, respectively. Attendance at cardiac rehabilitation (16.8% of patients with a first ACS, 10.8% with recurrent ACS) or a secondary prevention program (3.7% of ACS and 11.7% of stable CHD patients) was infrequent. CONCLUSIONS: The high prevalence of risk factors in all CHD patients and reduced rates of secondary prevention medications in stable CHD offer areas for improvement. TRANSLATIONAL ASPECTS: The findings of DYSIS II may reinforce the importance of adopting a healthy lifestyle and prescribing (by clinicians) and adhering (by patients) to evidence-based medications in the management of CHD, not only during the short term but also over the longer term after a cardiac ischemic event. The results may help to increase the proportion of ACS patients who are referred to cardiac rehabilitation centres.

Analysis of Episodes of Care in Medicare Beneficiaries Newly Diagnosed with Alzheimer's Disease.

OBJECTIVES: To study transitions between healthcare settings and quantify the cost burdens associated with different combinations of transitions during a 6-month period before initial Alzheimer's disease (AD) diagnosis so as to investigate how using an episode-of-care approach to payment for specific disease states might apply in AD. DESIGN: A retrospective observational cohort study. SETTING: United States. PARTICIPANTS: A random sample of 8,995 individuals aged 65 to 100 with a diagnosis of AD (International Classification of Diseases, Ninth Revision, Clinical Modification code 331.0) were identified from the Medicare database between January 1, 2011, and June 30, 2014. This analysis identified individuals with AD diagnosed in inpatient (18%), skilled nursing facility (SNF) (1%), hospice (4%), and home and outpatient (77%) settings and analyzed episodes that began in the index setting (defined as the care setting in which the individual was first diagnosed with AD). MEASUREMENTS: Study outcomes included number of transitions between settings, primary discharge diagnoses, and total all-cause healthcare costs during the 6 months after the AD diagnosis. RESULTS: The average numbers of transitions between care settings were 2.8 originating from an inpatient setting, 2.4 from a SNF, 0.3 from a hospice setting and 0.7 from a home or outpatient setting during 6 months post-AD diagnosis. The overall cost burden during the 6 months after AD diagnosis (including costs incurred at the index setting) was high for individuals diagnosed in a nonambulatory setting (mean $41,468). Individuals diagnosed in an ambulatory setting incurred only $12,597 in costs during the same period. CONCLUSION: Episodes of care can be defined and studied in individuals with AD. An episode-of-care approach to payment could encourage providers to use the continuum of care needed for quality medical management in AD more efficiently.

Quantifying the Diagnostic Pathway for Patients with Cognitive Impairment: Real-World Data from Seven European and North American Countries.

To ensure that patients with dementia and their caregivers receive appropriate treatment and support, early diagnosis is essential but remains challenging. Real-world data from a multi-national, cross-sectional survey of physicians and their patients were analyzed to quantify the diagnostic pathway for dementia, including a focus on severity of patients' cognitive impairment (CI) at the time of symptom onset, referral and subsequent diagnosis. Data were collected for 7,620 patients with CI. Most patients saw a healthcare professional within 1 year of first symptoms and received a diagnosis within 3-7 months of initial consultation. However, only 20% of patients received a diagnosis before their disease progressed beyond the prodromal stage and 23.5% already had moderate CI at diagnosis. These findings show that the goal of identifying and diagnosing CI at the earliest stages of disease is, for many patients, not achieved. Efforts toward public awareness and proactive, earlier detection and intervention, must be maintained-indeed where possible invigorated.

Economic Burden, Mortality, and Institutionalization in Patients Newly Diagnosed with Alzheimer's Disease.

BACKGROUND: Current information is scarce regarding comorbid conditions, treatment, survival, institutionalization, and health care utilization for Alzheimer's disease (AD) patients. OBJECTIVES: Compare all-cause mortality, rate of institutionalization, and economic burden between treated and untreated newly-diagnosed AD patients. METHODS: Patients aged 65-100 years with ≥1 primary or ≥2 secondary AD diagnoses (ICD-9-CM:331.0] with continuous medical and pharmacy benefits for ≥12 months pre-index and ≥6 months post-index date (first AD diagnosis date) were identified from Medicare fee-for-service claims 01JAN2011-30JUN2014. Patients with AD treatment claims or AD/AD-related dementia diagnosis during the pre-index period were excluded. Patients were assigned to treated and untreated cohorts based on AD treatment received post-index date. Total 8,995 newly-diagnosed AD patients were identified; 4,037 (44.8%) were assigned to the treated cohort. Time-to-death and institutionalization were assessed using Cox regression. To compare health care costs and utilizations, 1 : 1 propensity score matching (PSM) was used. RESULTS: Untreated patients were older (83.85 versus 81.44 years; p < 0.0001), with more severe comorbidities (mean Charlson comorbidity index: 3.54 versus 3.22; p < 0.0001). After covariate adjustment, treated patients were less likely to die (hazard ratio[HR] = 0.69; p < 0.0001) and were associated with 20% lower risk of institutionalization (HR = 0.801; p = 0.0003). After PSM, treated AD patients were less likely to have hospice visits (3.25% versus 9.45%; p < 0.0001), and incurred lower annual all-cause costs ($25,828 versus $30,110; p = 0.0162). CONCLUSION: After controlling for comorbidities, treated AD patients have better survival, lower institutionalization, and sometimes fewer resource utilizations, suggesting that treatment and improved care management could be beneficial for newly-diagnosed AD patients from economic and clinical perspectives.

Modelling total coronary heart disease burden and long-term benefit of cholesterol lowering in middle aged men with and without a history of cardiovascular disease.

Aims: Cumulative coronary heart disease (CHD) events over 20 years were examined in men screened for, and in those randomized to, the West of Scotland Coronary Prevention Study. Methods and results: Record linkage provided CHD-related events and days in hospital for the 80 230 screenees, including the randomized cohort of 6595 men. Risk factors were determined at baseline, and disease burden assessed for groups defined by cholesterol. Effects of cholesterol lowering were modelled from differences between groups, and from the treatment arms of the trial. Over 20 years, those without a history of CHD (n = 61 211) had 23.0 events per 100 subjects in the lowest cholesterol group (mean 4.0 mmol/L) and 65.1 per 100 in the highest (8.8 mmol/L). Corresponding days in hospital were 167.2-435.4 per 100 subjects. Analogous figures for men with a CHD history (n = 8570) were 77.3-141.7 events per 100 and 526.1-936.7 hospital days per 100. Lowering cholesterol by about 1.0 mmol/L in men with average cholesterol and no CHD was predicted to be associated with 8.9 fewer events and a saving of 56.0 hospital days per 100. In those with CHD this difference gave, depending on starting level, 26.8-36.5 fewer events and savings of 158.2-247.3 hospital days per 100 subjects. Comparison of cumulative events in 45-54 vs. 55-64 year olds in the trial revealed greater benefit from intervention in the younger decade. Conclusion: Long-term, longitudinal data reveal the considerable CHD burden in middle-aged men and indicate substantial clinical benefits from both moderate and aggressive cholesterol lowering.

Suboptimal achievement of low-density lipoprotein cholesterol targets in French patients with coronary heart disease. Contemporary data from the DYSIS II ACS/CHD study.

BACKGROUND: European guidelines recommend a low-density lipoprotein cholesterol (LDL-C) target of<1.8mmol/L (70mg/dL), and/or a≥50% reduction when the target level cannot be reached, for patients at very high cardiovascular risk, and high-potency lipid-lowering therapy (LLT) in patients with an acute coronary syndrome (ACS). AIM: To document the prevalence of lipid abnormalities and the achievement of lipid targets among patients surviving an ACS and in patients with stable coronary heart disease (CHD), using data from the DYSIS II study. METHODS: DYSIS II was an observational cross-sectional study conducted in 21 countries (2012-2014). We report data from the French cohort, comprising patients hospitalized with an ACS and patients diagnosed with stable CHD. Data on patient characteristics, risk factors, treatments and lipid profile were collected. LDL-C target achievement was assessed based on the European guidelines endorsed by the French Society of Cardiology. RESULTS: Of the 468 ACS patients, 277 (59.2%) were receiving LLT at admission to hospital; 22.6% were hospitalized for a recurrent event. Statins were used in 96.6% (450/466) of patients at discharge and in 95.1% (310/326) at 120-day follow-up, at which time 50.6% (80/158) of patients with available data achieved the LDL-C goal. Most of the 436 patients with stable CHD (97.2%) were on LLT (56.8% on high-intensity therapy); 29.2% of patients on LLT met the LDL-C treatment target<1.8mmol/L (70mg/dL). CONCLUSION: These observational data show the progress made in the treatment of ACS from the acute phase up to 3 months, and highlight key areas for improvement in the prevention of recurrent events in patients with CHD in France. The use of higher intensity or combination LLT as recommended in secondary prevention are needed to increase the achievement of LDL-C treatment targets and reduce the risk of morbidity and mortality due to CHD.

Impact of Switching From High-Efficacy Lipid-Lowering Therapies to Generic Simvastatin on LDL-C Levels and LDL-C Goal Attainment Among High-Risk Primary and Secondary Prevention Populations in the United Kingdom.

PURPOSE: High cholesterol, especially high low-density lipoprotein cholesterol (LDL-C), is an important risk factor for cardiovascular disease (CVD) morbidity/mortality. Switching from high-efficacy lipid-lowering therapies (HETs) to simvastatin might lead to sub-optimal control of LDL-C. Our objective was to evaluate the impact of switching from HETs to generic simvastatin on LDL-C levels and LDL-C goal attainment among the high-risk primary and secondary prevention populations in the United Kingdom. METHODS: This retrospective cohort study was conducted using Clinical Practice Research Datalink database. Included were individuals with more than 2 months of prescriptions of the following HETs between August 1, 2004 and December 31, 2008: simvastatin/ezetimibe fixed dose (S/E), simvastatin and ezetimibe co-administration (S+E), atorvastatin and ezetimibe co-administration (A+E), rosuvastatin and ezetimibe co-administration (R+E), rosuvastatin monotherapy, and atorvastatin monotherapy. For each baseline HET, we used analysis of covariance (ANCOVA) to estimate the least squares mean (LSM) difference in the percentage change from baseline in LDL-C between switchers and non-switchers, and logistic regression to estimate the odds ratio of attaining the LDL-C goal (<3 mmol/L for primary prevention and <2 mmol/L for secondary prevention, by JBS2) at follow-up. Propensity score adjusted analyses were conducted to reduce selection bias. FINDINGS: 30,148 patients met the eligibility criteria with 83.8% received atorvastatin, 9.5% rosuvastatin and 2.6% S/E and S+E combined. 89.1% of patients switching from atorvastatin switched to an equivalent or higher dose of simvastatin (dose equivalency was determined by relative efficacy of one statin to other statins), while 100% of those switching from simvastatin/ezetimibe and 96.8% of those switching from rosuvastatin switched to lower than equivalent dose of simvastatin. Compared to non-switchers, the adjusted least squares mean differences in the percentage change in LDL-C levels from baseline were 18.74% (p = 0.0003), 16.73% (p < 0.0001), and -0.11% (p = 0.9044) when switching from simvastatin/ezetimibe, rosuvastatin, and atorvastatin, respectively. The odds of LDL-C goal attainment at follow-up among switchers from simvastatin/ezetimibe, rosuvastatin, and atorvastatin were 0.40 (95% CI: 0.23-0.70), 0.36 (95% CI: 0.26-0.51) and 1.03 (95% CI: 0.92-1.15) relative to non-switchers respectively. IMPLICATIONS: Among the high risk CVD population in UK, switching to simvastatin from HET, especially rosuvastatin and simvastatin/ezetimibe, resulted in an increase in LDL-C levels and lower goal attainment. These historical data reinforce the appropriateness of the changes in the new Joint British Guideline (JBS3) which no longer recommends starting simvastatin 40 mg.

Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis.

OBJECTIVE: Evaluate the lipid-altering effects of ezetimibe added to ongoing statin therapy, statin titration, switching from statin monotherapy to a more potent statin or to ezetimibe/simvastatin. METHODS: A pooled analysis of patient-level data from 17 double-blind, active or placebo-controlled studies of 8667 hypercholesterolemic adults randomized to ezetimibe 10 mg added to ongoing statins, statin titration (doubling), or switching from ongoing statins to rosuvastatin (10 mg) or to ezetimibe/simvastatin (10/20 and 40 mg). Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) was estimated by analysis of variance. Percent of patients who achieved LDL-C and other guideline-recommended targets, and target lipid levels by baseline distance to goal were evaluated. RESULTS: LDL-C percent change from baseline was -26.0 for ezetimibe added to ongoing statin therapy, -27.6 for switching from ongoing statin to ezetimibe/simvastatin, -19.7 for switching to rosuvastatin 10 mg, and -9.7 for dose doubling of the ongoing statin. For patients within 0.8 mmol/L (30 mg/dL) of the target at baseline, LDL-C target attainment rates were 75.9% for adding ezetimibe to ongoing statin, 72.8% for switching to ezetimibe/simvastatin, 61.8% for switching to rosuvastatin, and 44.3% for statin dose-doubling. Similarly, improvements in other lipids and achievement of non-high-density lipoprotein cholesterol and apolipoprotein B targets among this patient group were largest for ezetimibe added to ongoing statins and switching to ezetimibe/simvastatin; switching to rosuvastatin 10 mg and statin dose-doubling were less effective. CONCLUSIONS: Adding ezetimibe to ongoing statin therapy appeared to be an effective option for patients who do not achieve lipid-lowering goals on statins alone.

Factors influencing dyslipidemia in statin-treated patients in Lebanon and Jordan: results of the Dyslipidemia International Study.

BACKGROUND: Cardiovascular disease is the leading cause of death and disability worldwide. Therefore, as part of the Dyslipidemia International Study (DYSIS), we have analyzed the prevalence of lipid abnormalities and risk factors for dyslipidemia in statin-treated patients in Lebanon and Jordan. METHODS: This cross-sectional, multicenter study enrolled 617 patients at 13 hospitals in Lebanon and Jordan. Patients were at least 45 years old and had been treated with statins for at least 3 months. Multivariate logistic regression analysis was used to determine patient characteristics contributing to dyslipidemia during statin therapy. RESULTS: Our findings indicated that 55.9% of statin-treated patients (mean age 60.3 years, 47% female) in Lebanon and Jordan did not achieve goal levels for low-density lipoprotein cholesterol which were dependent on Systematic Coronary Risk Evaluation (SCORE) risk, and 70% of patients (76% men and 63.3% of women) were at very high cardiovascular risk. Low-density lipoprotein cholesterol goals were not achieved in 67.2% of those with very high cardiovascular risk. The most commonly prescribed statin was atorvastatin (44.6%), followed by simvastatin (27.7%), rosuvastatin (21.2%), fluvastatin (3.3%), pravastatin (3%), and lovastatin (0.2%). Approximately half of the population was treated with a statin dose potency of 4, equaling 40 mg of simvastatin. In Lebanon and Jordan, the strongest independent associations with low-density lipoprotein cholesterol not at goal were current smoking (odds ratio [OR] 1.96; 95% confidence [CI] 1.25-3.08), diabetes mellitus (OR 2.53; 95% CI 1.70-3.77), and ischemic heart disease (OR 2.26; 95% CI 1.45-3.53), while alcohol consumption was associated with reduced risk (OR 0.12; 95% CI 0.03-0.57). CONCLUSION: We observed that many patients in Lebanon and Jordan experienced persistent dyslipidemia during statin treatment, supporting the notion that novel lipid-lowering strategies need to be developed. Also, social programs aimed at combating the extremely high rates of tobacco use and obesity in Lebanon and Jordan are critical for combating cardiovascular disease in these countries.

Association of a reduction in low-density lipoprotein cholesterol with incident cardiovascular and cerebrovascular events among people with type 2 diabetes mellitus.

BACKGROUND: Although there is overwhelming evidence that reducing low-density lipoprotein cholesterol (LDL-C) with statins leads to reductions in cardiovascular disease, less is known about the effects in persons with type 2 diabetes mellitus (T2DM) without pre-existing vascular events. METHODS AND RESULTS: Using the UK-based General Practice Research Database we conducted a retrospective cohort study of 21,998 T2DM patients aged 35-69 with ≥2 prescriptions for lipid-modifying therapy (2000-2009). We categorized LDL-C change (mmol/l) between last available and baseline lipid values as reduction (≥3.0, 2.0-2.9, 1.0-1.9, 0.3-0.9), no-change (±0.2 of baseline), or increase (>0.2). Outcomes were incident composite cardiovascular (n = 621) and cerebrovascular events (n = 274). We estimated hazard ratios (HRs) of study outcomes and 95% confidence intervals (CIs) for LDL-C change compared with the no-change group. Compared to no changes, adjusted HRs of cardiovascular events for a reduction ≥3.0 and a reduction between 2.0-2.9 were 0.41 (95% CI: 0.23-0.71) and 0.51 (95% CI: 0.34-0.76) (p for linear trend <0.001). LDL-C reduction yielded a decreased cerebrovascular event risk compared to no change, even with the smallest reduction (adjusted HR = 0.59, 95% CI: 0.36-0.98). CONCLUSIONS: Decreasing LDL-C is associated with a reduced risk of cardiovascular and cerebrovascular events among T2DM patients without such pre-existing events. The magnitude of the protective effect on cerebrovascular events is less certain, and further studies are warranted.

Attainment of normal lipid levels among high cardiovascular risk patients: pooled analysis of observational studies from the United Kingdom, Sweden, Spain and Canada.

BACKGROUND: Although low-density lipoprotein cholesterol (LDL-C) is the primary lipid target for cardiovascular disease (CVD) risk reduction, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) have also emerged as risk factors. This study evaluated attainment of goal/normal lipid levels in current clinical practice among high-risk patients following lipid-modifying therapy (LMT). METHODS: Data for patients aged ≥35years and on LMT for ≥12months were identified from electronic medical records (United Kingdom and Sweden) and extracted from medical charts (Canada and Spain). High CVD risk was defined according to the Adult Treatment Panel III guidelines. An index period was defined, from January 1995-July 2008, during which patients received an initial LMT prescription. Prevalence of lipid abnormalities was assessed 12months before and after the index date. Multivariate logistic regressions evaluated predictors of attaining goal/normal lipid levels. RESULTS: Among 12,768 high-risk patients, 75% had elevated LDL-C, 37% low HDL-C, and 30% elevated TG before LMT. Despite therapy (97% statins only), 23% had elevated LDL-C, 36% low HDL-C, 16% elevated TG, and 17% had ≥2 abnormal lipid levels. Framingham risk score >20% (Odds Ratio, 95% confidence interval: 0.37,0.31-0.43), diabetes (0.75,0.64-0.88), hypertension (1.26,1.09-1.46), current smoker (0.82,0.70-0.95) and increased body mass index (0.95,0.94-0.96) were associated with the likelihood of attaining ≥2 normal lipid levels (vs. LDL-C goal only). CONCLUSION: Current approaches to lipid management improve LDL-C goal attainment; however, control of multiple lipid risk factors remains poor. Patients may benefit from more comprehensive approaches to lipid management, which treat multiple lipid abnormalities, as suggested in clinical guidelines.

Attainment of goal and normalized lipid levels with lipid-modifying therapy in Malaysia.

BACKGROUND: Although LDL-C is the primary lipid target for coronary heart disease (CHD) risk reduction, HDL-C and triglycerides (TG) have also emerged as CHD risk factors. OBJECTIVE: The objective of this study was to evaluate goal/normal lipid level attainment after lipid-modifying therapy (LMT) in an ethnically diverse sample of patients in Malaysia. METHODS: Retrospective, longitudinal data were collected from the medical records of patients aged ≥35 years in whom LMT was initiated between January 2004 and December 2006. Eligible patients had records of full lipid panels 12 months before and after the start of therapy. LDL-C goals and normal levels of HDL-C and TG were defined as per the Clinical Practice Guidelines on Management of Dyslipidemia (4th edition), Malaysia. A subgroup of patients at high risk for CHD events (established CHD, diabetes but no CHD, or a 10-year history of Framingham risk score ≥20%) was also studied. RESULTS: Among 607 eligible patients (mean age, 57.1 years; 40% male), 89% had elevated LDL-C, 37% had low HDL-C, 56% had elevated TG, and 62% had ≥2 abnormal lipid levels before LMT. Despite therapy (87% statins only), 60% had elevated LDL-C, 37% had low HDL-C, 40% had elevated TG, and 44% continued to have ≥2 abnormal lipid levels. CONCLUSIONS: In this longitudinal study of Malaysian patients treated with lipid-modifying therapy, primarily using statins, attainment of LDL-C goal is suboptimal. Furthermore, a large proportion of patients do not achieve normal levels of HDL-C and TG. Therefore, patients may benefit from a more comprehensive approach to lipid management that treats all 3 lipid risk factors, as suggested in clinical guidelines.

Mixed dyslipidemias in primary care patients in France.

OBJECTIVE: To determine the prevalence of single and mixed dyslipidemias among patients treated with statins in clinical practice in France. METHODS: This is a prospective, observational, cross-sectional, pharmacoepidemiologic study with a total of 2544 consecutive patients treated with a statin for at least 6 months. MAIN OUTCOME MEASURES: Prevalence of isolated and mixed dyslipidemias of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides among all patients and among patients at high cardiovascular risk; clinical variables associated with attainment of lipid targets/normal levels in French national guidelines. RESULTS: At least one dyslipidemia was present in 50.8% of all patients and in 71.1% of high-risk patients. Dyslipidemias of LDL-C, HDL-C, and triglycerides were present in 27.7%, 12.4%, and 28.7% of all patients, respectively, and in 51.0%, 18.2%, and 32.5% of high-risk patients, respectively. Among all subjects with any dyslipidemia, 30.9% had mixed dyslipidemias and 69.4% had low HDL-C and/or elevated triglycerides, while 30.6% had isolated elevated LDL-C; corresponding values for high-risk patients were 36.8%, 58.9%, and 41.1%. Age, gender, body mass index and Framingham Risk Score >20% were the factors significantly associated with attainment of normal levels for ≥2 lipid levels. CONCLUSIONS: At least one dyslipidemia persisted in half of all patients and two-thirds of high cardiovascular risk patients treated with a statin. Dyslipidemias of HDL-C and/or triglycerides were as prevalent as elevated LDL-C among high cardiovascular risk patients.