Skin improvement is a surrogate for favourable changes in other organ systems in early diffuse cutaneous systemic sclerosis.

OBJECTIVES: Skin improvement in diffuse cutaneous SSc (dcSSc), measured with modified Rodnan skin score (mRSS), is frequently used as a primary outcome in clinical trials, but it is uncertain whether mRSS changes reflect changes in other organ systems. This aim of this study was to explore if skin changes in early dcSSc over 1 and 2 years are associated with changes in severity of other organ involvement. METHODS: Canadian Scleroderma Research Group database patients with dcSSc, disease duration of ≤5 years, no evidence of initial end-stage organ damage and/or significant comorbidity who had 1 year (n = 154) and 2 years (n = 128) of follow-up data were included. mRSS changes of 25% and/or ≥5 points were considered significant. Organ involvement was assessed by Medsger Disease Severity Score and Canadian Scleroderma Research Group definitions using bivariate, chi-square, ANOVA, adjusted regression and longitudinal mixed effect model analyses. RESULTS: Improvement in mRSS was found in 41% of patients at 1 year and in 50% at 2 years. Improved patients showed less forced vital capacity decline (P = 0.012) and less frequent new cardiac involvement (P = 0.02) over 1 year, as well as better lung (by both Disease Severity Score, P = 0.006, and Δforced vital capacity%, P = 0.026), peripheral vascular (P = 0.006) and joint/tendon (P = 0.002) involvement over 2 years. mRSS worsening was consistently linked to less favourable lung outcomes at both 1- and 2-year follow-up visits, and more severe gastrointestinal disease at 2 years. CONCLUSION: Changes in lung function in early dcSSc closely parallel skin changes. mRSS improvement reflects better prognosis for visceral disease and may be a reliable outcome measure in clinical trials.

Changes in skin score in early diffuse cutaneous systemic sclerosis are associated with changes in global disease severity.

OBJECTIVE: To determine whether skin score changes are associated with changes in overall disease severity, function and quality of life in early dcSSc patients. METHODS: A total of 154 and 128 dcSSc patients from the Canadian Scleroderma Research Group database with 1 and 2 year follow-up and a disease duration ⩽5 years without end-stage organ damage and/or significant comorbidity at the initial visit were included. Skin was assessed using the modified Rodnan skin score (mRSS) and disease severity by the summed Medsger disease severity score (DSS) (without skin domain), physician and patient global assessments, function [HAQ disability index (HAQ-DI)] and quality of life [36-item Short Form Health Survey (SF-36) physical component summary (PCS)]. Analyses were repeated in patients with a disease duration ⩽3 years. RESULTS: At 2 years, 64 (50%) patients had improved skin (mRSS decrease of ⩾5 points and/or ⩾25%). Skin improvers had improved summed DSS (P = 0.002); better physician global assessments of disease activity, severity and damage (all P ⩽ 0.003); better HAQ-DI (P = 0.001) and SF-36 PCS (P = 0.005). Changes in the mRSS were positively correlated with changes in summed DSS (P = 0.006) and other disease outcomes. In the 26 (20.3%) patients with worsened skin (mRSS increase of ⩾5 points and/or ⩾25%), the summed DSS and physician global assessments were worse (P = 0.01 and P ⩽ 0.009, respectively). In the subgroup with a disease duration ⩽3 years, similar associations were found. CONCLUSION: At 1 and 2 years, overall disease improvement parallels skin improvement in early dcSSc. This is important for prognosis and reflects the value of mRSS as an outcome measure in trials with these patients.

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.

Low-Density Lipoprotein Cholesterol Goal Attainment Rates by Initial Statin Monotherapy Among Patients With Dyslipidemia and High Cardiovascular Risk in Japan　- A Retrospective Database Analysis.

BACKGROUND: To understand the recent management status in Japan, we determined the low-density lipoprotein cholesterol (LDL-C) goal attainment (GA) rate of patients initiating statin monotherapy for dyslipidemia.Methods and Results:Dyslipidemic patients undergoing either primary prevention with high cardiovascular risk or secondary prevention (defined by 2012 Japan Atherosclerosis Society Guidelines) were retrospectively analyzed from a hospital-based claims database. In both groups, the LDL-C levels and GA rates of patients treated with intensive or standard statin monotherapy for ≥4 weeks (January 2012-August 2016) were evaluated. Among 1,501,013 dyslipidemic patients, 11,695 and 9,642 were included in the primary and secondary prevention groups, respectively. A total of 94% of patients underwent statin monotherapy as the initial lipid-lowering therapy, of which most (≥80%) took intensive statins. The proportions of patients in the primary prevention group who achieved an LDL-C goal <120 mg/dL by intensive and standard statins were 81.1% and 61.2%, respectively, and the proportions of those who achieved a goal <100 mg/dL in the secondary prevention group were 73.3% and 48.1%, respectively. The GA rates were similar regardless of disease complications. CONCLUSIONS: Most patients (>70%) in both groups achieved LDL-C management goals using intensive statin monotherapy. Further treatment approaches are required for high-risk patients not achieving LDL-C goals by initial statin monotherapy. Continuous efforts are crucial for adherence and persistence of lipid-lowering therapies.

Cardiovascular events and all-cause mortality associated with sulphonylureas compared with other antihyperglycaemic drugs: A Bayesian meta-analysis of survival data.

AIM: To conduct a systematic review and meta-analysis to determine the risk of cardiovascular events and all-cause mortality associated with sulphonylureas (SUs) vs other glucose lowering drugs in patients with T2DM (T2DM). MATERIALS AND METHODS: A systematic review of Medline, Embase, Cochrane and clinicaltrials.gov was conducted for studies comparing SUs with placebo or other antihyperglycaemic drugs in patients with T2DM. A cloglog model was used in the Bayesian framework to obtain comparative hazard ratios (HRs) for the different interventions. For the analysis of observational data, conventional fixed-effect pairwise meta-analyses were used. RESULTS: The systematic review identified 82 randomized controlled trials (RCTs) and 26 observational studies. Meta-analyses of RCT data showed an increased risk of all-cause mortality and cardiovascular-related mortality for SUs compared with all other treatments combined (HR 1.26, 95% confidence interval [CI] 1.10-1.44 and HR 1.46, 95% CI 1.21-1.77, respectively). The risk of myocardial infarction was significantly higher for SUs compared with dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose co-transporter-2 inhibitors (HR 2.54, 95% CI 1.14-6.57 and HR 41.80, 95% CI 1.64-360.4, respectively). The risk of stroke was significantly higher for SUs than for DPP-4 inhibitors, glucagon-like peptide-1 agonists, thiazolidinediones and insulin. CONCLUSIONS: The present meta-analysis showed an association between SU therapy and a higher risk of major cardiovascular disease-related events compared with other glucose lowering drugs. Results of ongoing RCTs, which should be available in 2018, will provide definitive results on the risk of cardiovascular events and all-cause mortality associated with SUs vs other antihyperglycaemic drugs.

Assessing the impact of kidney cancer-related premature mortality and productivity loss in Greece and Portugal.

OBJECTIVE: In 2018, 371,750 people were diagnosed with kidney cancer globally, constituting 2.2% of all cancer diagnoses. Since 2010, the number of kidney cancer deaths in Europe have decreased in people under 65. However, this is not the case in Greece and Portugal. This study estimated the mortality and lost productivity due to premature mortality from kidney cancer in Greece and Portugal. METHODS: Years of life lost (YLL) and present value of future lost productivity (PVFLP) due to kidney cancer mortality (ICD-10 code: C64 - Malignant neoplasm of kidney, except renal pelvis) were calculated using the human capital approach. Age-specific mortality, mean earnings, and labor force participation rates were used in these calculations. RESULTS: In 2019, there were 564 and 454 kidney cancer deaths in Greece and Portugal, respectively, resulting in 5,871 (3,636 in males and 2,234 in females) and 5,397 (3,100 in males and 2,297 in females) YLL, respectively. YPLL and annual PVFLP were estimated to be 1,326 and €14.8 M in Greece and 1,278 and €11.8 M in Portugal, respectively. CONCLUSION: YLL and PVFLP due to kidney cancer mortality are substantial in Greece and Portugal. These results provide new evidence to assist decision-makers in allocating resources to reduce cancer burden.

Indirect Costs Due to Lung Cancer-Related Premature Mortality in Four European Countries.

INTRODUCTION: Lung cancer accounts for approximately 20% of all cancer-related deaths and for the loss of 3.2 million disability-adjusted life years (DALYs) annually across Europe. The present study investigated the productivity losses resulting from premature deaths due to lung cancer in four European countries. METHODS: The human capital approach (HCA) was used to estimate indirect cost of productivity losses due to premature death due to lung cancer (ICD-10 codes C33-34 malignant neoplasm of trachea, bronchus, and lung) in Belgium, the Netherlands, Norway, and Poland. Years of productive life lost (YPLL) and present value of future lost productivity (PVFLP) were calculated using national age-specific mortality, wages, and employment rates. Data were sourced from the World Health Organization, Eurostat, and the World Bank. RESULTS: In 2019, there were 41,468 lung cancer deaths in the included countries resulting in 59,246 YPLL and more than €981 million in productivity losses due to premature mortality. From 2010 to 2015, the PVFLP of lung cancer decreased by 14% in Belgium, 13% in the Netherlands, 33% in Norway, and 19% in Poland. From 2015 to 2019, the PVFLP of lung cancer decreased by 26% in Belgium, 27% in the Netherlands, 14% in Norway, and 38% in Poland. CONCLUSION: The results from this study illustrate a decreasing trend in productivity costs of premature mortality due to lung cancer, as illustrated by the decreasing PVFLP between 2010 and 2019. This trend could be driven by a shift in the distribution of deaths towards older age groups due to advancements in the preventative and treatment landscape. These results provide an economic measure of the lung cancer burden which may assist decision-makers in allocating scarce resources amongst competing priorities in the included countries.

Breast cancer-related mortality in Central and Eastern Europe: years of life lost and productivity costs.

BACKGROUND: Breast cancer (BC) poses a public health challenge as the most commonly diagnosed cancer among women globally. While BC mortality has declined across Europe in the past three decades, an opposite trend has been reported in some transitional European countries. This analysis estimates the mortality burden and the cost of lost productivity due to BC deaths in nine Central and Eastern Europe (CEE) countries: Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia, that have defied the favorable cancer mortality trends. These estimates may provide relevant evidence to aid decision-makers in the prioritization of BC-targeted policies. METHODS: The human capital approach (HCA) was used to estimate years of life lost (YLL) and productivity losses due to premature death from BC (ICD-10 code: C50 Malignant neoplasm of breast). YLL and present value of future lost productivity (PVFLP) were calculated using age and gender-specific mortality, wages, and employment rates. Data were sourced from the World Health Organization (WHO), Eurostat, and the World Bank. RESULTS: In 2019, there were 19,726 BC deaths in the nine CEE countries. This study estimated BC deaths resulted in 267,184 YLL. Annual PVFLP was estimated to be €85 M in Poland, €46 M in Romania, €39 M in Hungary, €21 M in Slovakia, €18 M in Serbia, €16 M in Czech Republic, €15 M in Bulgaria, €13 M in Croatia, and €7 M in Slovenia. CONCLUSION: Premature death from BC leads to substantial YLL and productivity losses. Lost productivity costs due to premature BC-related mortality exceeded €259 million in 2019 alone. The data modeled provide important evidence toward resource allocation priorities for BC prevention, screening, and treatment that could potentially decrease productivity losses. Careful consideration should be given to BC-specific policies, such as surveillance programs and the availability of new treatments in CEE countries to decrease the medical and financial burden of the disease.

Economic evaluation of doravirine/tenofovir disoproxil fumarate/lamivudine for HIV-1-infected adults in Russia: a cost-minimization and budget impact analysis.

BACKGROUND: In Russia, before 2022, the list of vital and essential drugs for HIV-infected patients previously untreated with antiretroviral drugs included the fixed-dose combination rilpivirine/tenofovir disoproxil fumarate/emtricitabine (RPV/TDF/FTC) but not doravirine/tenofovir disoproxil fumarate/lamivudine (DOR/TDF/3TC). METHODS: An indirect comparison of the efficacy of DOR/TDF/3TC and RPV/TDF/FTC defined by virologic suppression (HIV-1 RNA of <50 copies/mL at week 48) was made. The per-patient drug costs over 1 year were compared in a cost-minimization analysis. A budget impact analysis considered the costs to the healthcare system of including DOR/TDF/3TC as a treatment option for eligible patients in Russia over a 3-year time horizon. RESULTS: The indirect treatment comparison of DOR/TDF/3TC and RPV/TDF/FTC in treatment-naïve patients with baseline HIV-1 RNA 100,000 copies/ml or less showed no statistically significant difference (RR 0.914, 95% CI 0.833-1.003). In the cost-minimization analysis, the per-patient cost of one year of treatment with RPV/TDF/FTC and DOR/TDF/3TC was, respectively, ₽320,975 and ₽151,192, for a saving of ₽169,783. In the budget impact analysis, the adoption of DOR/TDF/3TC into clinical practice is expected to reduce drug costs by ₽333 million (23.8%) in year 3. CONCLUSIONS: Fixed-dose combination DOR/TDF/3TC is equally effective and cost-saving compared to RPV/TDF/FTC from Russian vital and essential drugs list perspective.

The demographics, clinical characteristics and quality of life of patients with chronic cough from the Isala Cough Clinic in the Netherlands.

Introduction: Chronic cough affects ∼10% of the population and adversely impacts quality of life. This retrospective observational cohort study aimed to identify the demographics, clinical characteristics and quality of life of the chronic cough population in a Dutch chronic cough clinic, at baseline and following treatment at 6 months. Patients were categorised based on the underlying phenotype and response to treatment. Methods: Retrospective data on 2397 patients who were diagnosed according to standard guidelines of the American College of Chest Physicians were analysed. Quality of life was captured via the Leicester Cough Questionnaire, the Cough Numeric Rating Scale and the Hospital Anxiety and Depression Scale. Results: Mean patient age was 59 years; 62.5% of the patients were female; and 69.1% had at least one underlying phenotype associated with chronic cough. Of the latter, 52.1% had bronchial hyperresponsiveness/airflow limitation, 33.3% had airway reflux and 20.1% had upper airway cough syndrome. 46% of patients with a phenotype, and 51% without, experienced no improvement in their quality of life or still had significant cough remaining after 6 months. Of patients with available quality-of-life data, 37.5% were categorised as having refractory chronic cough, and 9.5% were categorised as unexplained chronic cough. Discussion: This study highlights the poor quality-of-life outcomes in patients with chronic cough, despite interventions to treat underlying conditions, and indicates a need to manage chronic cough irrespective of phenotype.

Reaction development and mechanistic study of a ruthenium catalyzed intramolecular asymmetric reductive amination en route to the dual Orexin inhibitor Suvorexant (MK-4305).

The first example of an intramolecular asymmetric reductive amination of a dialkyl ketone with an aliphatic amine has been developed for the synthesis of Suvorexant (MK-4305), a potent dual Orexin antagonist under development for the treatment of sleep disorders. This challenging transformation is mediated by a novel Ru-based transfer hydrogenation catalyst that provides the desired diazepane ring in 97% yield and 94.5% ee. Mechanistic studies have revealed that CO(2), produced as a necessary byproduct of this transfer hydrogenation reaction, has pronounced effects on the efficiency of the Ru catalyst, the form of the amine product, and the kinetics of the transformation. A simple kinetic model explains how product inhibition by CO(2) leads to overall first-order kinetics, but yields an apparent zero-order dependence on initial substrate concentration. The deleterious effects of CO(2) on reaction rates and product isolation can be overcome by purging CO(2) from the system. Moreover, the rate of ketone hydrogenation can be greatly accelerated by purging of CO(2) or trapping with nucleophilic secondary amines.

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.

A mild and efficient one-pot synthesis of 2-aminated benzoxazoles and benzothiazoles.

Previous syntheses of the biologically active 2-aminated benzoxazoles have relied on forcing thermal conditions to generate the products directly from the corresponding thiols. The resulting yields have ranged from moderate to poor. A mild and high-yielding alternative one-pot chlorination-amination procedure is described. Compounds with a variety of substitution patterns are reported and the methodology has been successfully extended to benzothiazoles. Palladium catalysis on suitably activated examples has been employed to generate the desired compounds of interest.

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.

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.

Contemporary data on treatment practices for low-density lipoprotein cholesterol in 3867 patients who had suffered an acute coronary syndrome across the world.

DYSIS II ACS was a longitudinal, observational study in 3867 patients from 18 countries. They were being hospitalized after suffering an acute coronary syndrome. Evaluations were performed at the time of admission and again 120±15 days following the date of admission (the follow-up time point). 2521 patients were on active lipid lowering treatment (LLT) at admission. Mean atorvastatin dose was 22 mg per day and 2.7% received ezetimibe in combination with a statin. At discharge from hospital, 3767 patients received LLT expressed as a mean atorvastatin dose of 36 mg per day with 4.8% receiving ezetimibe on top of a statin. After 120 days, intensity in lipid lowering treatment was reduced to 32 mg per day with 4.9% of the patients receiving ezetimibe and a statin. Of note, during this 4-month follow up period, only 32% of all patients received laboratory lipid testing. 37% attained the low density lipoprotein cholesterol (LDL-C) target value of <70 mg/dl after 120 days. There are differences in the therapy administered as well as in the switch strategies when comparing the data from the respective countries studied. CONCLUSIONS: Only one in three patients achieved the LDL-C target value following only marginal improvements in atorvastatin dose or combination therapy after an ACS event.

Prevalence of lipid abnormalities and cholesterol target value attainment in patients with stable coronary heart disease or an acute coronary syndrome in Saudi Arabia.

OBJECTIVES: To provide an overview of the extent of hyperlipidemia in very high-risk patients, and how lipid-lowering therapy (LLT) is used in a real-world setting. Methods: In this multicenter observational study, data were collected from LLT-treated patients with stable CHD or an ACS in Saudi Arabia between 2013 and 2014. Individuals were included if they were greater than 18 years and had a full lipid profile available, recorded either prior to the baseline physician visit (CHD patients) or within 24-hours of admission to hospital (ACS patients).  Results: A total of 737 patients were included in the study, 597 with stable CHD and 140 with ACS. Few patients in either group had an LDL-C level of greater than 70 mg/dl, which is advocated for very high-risk patients (24.3% and 11.4%, respectively). The median distances to this value were 19.0 mg/dl (CHD) and 25.0 mg/dl (ACS). Low doses of statins were being utilized (31 and 24 mg/day for CHD and ACS, respectively), with only minimal intensification for the ACS patients after hospital admission (41 mg/day at follow-up). Conclusions: Achievement of recommended LDL-C levels was poor for patients with stable CHD or an ACS. Statin intensity was low, indicating huge scope for intensifying the treatment of these very high-risk patients.

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.

Contemporary data on treatment practices for low-density lipoprotein cholesterol in 6794 patients with stable coronary heart disease across the world.

DYSIS II CHD was a longitudinal, observational study in 6794 patients from 18 countries. They were attending an outpatient physician appointment for coronary heart disease (CHD). 6370 patients (93.8%) were on active lipid lowering therapy (LLT). The mean atorvastatin dose equivalent was 25 mg per day and 10.5% received ezetimibe in combination with a statin. The mean low-density lipoprotein cholesterol (LDL-C) level was 88 mg/dL, with 29.4% of patients displaying a level below the 70 mg/dL target for very high-risk subjects. CONCLUSION: While more than 90% of patients with CHD were on lipid lowering drugs, only three out of ten patients achieved their LDL-C target value.