Outcomes of adding second hypoglycemic drug after metformin monotherapy failure among type 2 diabetes in Hungary.

AIM: The objective of this observational study was to assess the status of glycemic control and associated patient-reported outcomes in ambulatory Hungarian patients with type 2 diabetes mellitus (T2DM) who were prescribed either a sulfonylurea (SU) or a thiazolidinedione (TZD) in addition to the prior metformin (MF) monotherapy. METHODS: Type 2 diabetics aged > or = 30 years and who had added an SU or TZD to previous MF monotherapy at least 1 year prior to the visit date were identified during January 2006 to March 2007. Information on HbA1c (A1C), medication use and co-morbid conditions was extracted from the medical record up to 6 months prior to the addition of SU or TZD to MF (baseline), and a minimum of one year after the initiation of either SU or TZD. Glycemic control (A1C < 6.5%) was assessed using the last available A1C value in the medical record. Self-reported hypoglycemia, health-related quality of life (HRQoL) and treatment satisfaction were also assessed. RESULTS: A total of 414 patients (82% SU+MF and 18% TZD+MF) with a mean age of 60.5 years (SD = 9.4 years) participated in the study. About 27% of patients reported hypoglycemic episodes, with about one-third reporting episodes that resulted into interruption of activities or required medical/non-medical assistance. Three quarters of patients were not at glycemic goal and BMI was the only factor significantly associated with failure to have an A1C level < 6.5%. Patients' HRQoL was significantly associated with self-reported hypoglycemic episodes (p = 0.017), and duration of diabetes (p = 0.045). CONCLUSION: Nearly 75% of patients were not at A1C goal of < 6.5% despite using two oral anti-hyperglycemic medications. Approximately 9% of patients reporting hypoglycemia required some kind of medical/non-medical assistance. Greater BMI at baseline was associated with an A1C level > or = 6.5%. Finally, self- reports of hypoglycemia and duration of diabetes were associated with low HRQoL.

Cholesterol goal attainment in patients with coronary heart disease and elevated coronary risk: results of the Hong Kong hospital audit study.

OBJECTIVE: We sought to determine 1) long-term lipid-lowering treatment patterns; 2) cholesterol goal attainment rates and possible determinants of goal achievement; and 3) effects of cholesterol goal attainment on coronary events in hospitalized Hong Kong patients. METHODS: In this retrospective cohort analysis, records of two public Hong Kong hospitals were reviewed for 196 adults (69% with coronary heart disease (CHD) or CHD-risk equivalent) who received at least one lipid-lowering therapy during hospitalization. Low-density lipoprotein cholesterol (LDL-C) targets were <2.6 mmol/l (<100 mg/dL) for patients with CHD or CHD risk equivalents and <3.37 mmol/l (<130 mg/dL) for those without. RESULTS: Most participants were initiated on regimens of low to midequipotency doses and never had their regimens adjusted to higher potency. Approximately 44% of patients not at LDL-C at baseline failed to achieve goal during a median follow-up of 1.9 years. Patients with higher coronary risk and/or LDL-C levels at baseline were less likely than their lower-risk counterparts to achieve goal; for each 1-mmol/l (38.7-mg/dL) increase in LDL-C at baseline, the likelihood of attaining goal declined by 64%. Patients achieving cholesterol goal had significantly longer cardiovascular event-free times. CONCLUSIONS: A total of 44% of Hong Kong patients not at LDL-C goals at baseline did not achieve them over 1.9 years. More effective and well-tolerated therapies, including adjunctive regimens (e.g., ezetimibe-statin, niacin-statin), may be necessary to enhance LDL-C goal achievement and increase event-free time.

Impact of new Joint British Societies' (JBS 2) guidelines on prevention of cardiovascular disease: evaluation of serum total cholesterol goal achievement in UK clinical practice.

BACKGROUND: Consensus health panels, including the Joint British Societies (JBS), have established increasingly stringent cholesterol goals. However, in clinical settings, most patients do not achieve even the less stringent goals. OBJECTIVE: To provide descriptive data on the proportion of patients in the United Kingdom who would have achieved the new JBS 2 total cholesterol (TC) goal of < 4.0 mmol/L (< 155 mg/dL) without changes in therapy. METHODS: Cross-sectional analysis of patients initiated on lipid-modifying therapies in 2005 (before publication of the JBS 2 guidelines), as ascertained via a physician (general practitioner (GP)) database. RESULTS: Among 70,194 patients (mean age 64 years) receiving prescriptions for lipid-modifying therapies, 35,823 (51.0%) were considered to be at high risk because of CHD or diabetes mellitus and 34,371 (49.0%) were at low risk. A total of 66,642 (94.9%) patients received monotherapy with HMG-CoA reductase inhibitors (statins), including 33,853 (94.5%) of high-risk patients and 32,789 (95.4%) low-risk individuals. Statins were prescribed at medium (maximum daily dose = simvastatin 40 mg; atorvastatin 20 mg; rosuvastatin 10 mg) or lower equipotency doses in the majority of patients receiving these medications -58,033 (87.1%) patients receiving statins, including 28,988 (85.6%) high-risk patients and 29,045 (88.6%) low-risk patients. Of the 28,874 patients with TC measurements, 7827 (27.1%) would have achieved the new JBS 2 goal without changes in medications or doses. In more than 51% of patients, TC values were > or = 10% above the JBS 2 target despite prescribed therapy, suggesting that these individuals would also not have achieved the JBS 2 goal by doubling their statin doses. CONCLUSIONS: Even though patient data were accessed before the JBS 2 guidelines were issued and data on other cardiovascular risk factors not captured, it can be concluded that most British patients (approximately 73%) would not have achieved the recent JBS 2 TC target of < 4.0 mmol/L without changes in lipid-modifying medications or medication doses. More effective and well-tolerated treatments, including combination statin regimens, are needed to increase the proportion of British patients reaching the more stringent JBS 2 goal.

The A-SACT (Achievement in Singapore of Cholesterol Targets) study in patients with coronary heart disease.

BACKGROUND: Cardiovascular disease remains a leading cause of death worldwide, with hypercholesterolemia being a major risk factor. Evidence-based consensus guidelines have recommended consideration of increasingly stringent cholesterol-lowering goals, yet most patients do not meet these targets. Coronary heart disease (CHD) event and mortality rates and mean serum cholesterol levels have declined in Singapore in recent years; however, certain groups remain at elevated risk. OBJECTIVE: To determine (i) proportions of patients with CHD in Singapore who achieved goals for serum low-density lipoprotein-cholesterol (LDL-C); and (ii) factors influencing goal attainment. METHODS: A historical cohort study was conducted using records from the Singapore Cardiac Databank, a national registry of CHD patients. Serum LDL-C goal attainment was assessed in 5174 survivors of acute myocardial infarction or coronary revascularization (i.e. coronary artery bypass graft surgery or percutaneous coronary interventions), of whom 3811 (73.7%) were at very high risk. RESULTS: At baseline, the mean patient age was 60.3 years, mean serum value of total cholesterol was 228 mg/dL, and mean LDL-C was 163 mg/dL. Of all CHD patients, approximately 70% did not achieve a serum LDL-C target of <100 mg/dL. Most patients receiving HMG-CoA reductase inhibitor (statin) regimens were treated initially with low- to medium-equipotency regimens and were never titrated to stronger regimens. The vast majority (approximately 94%) of patients at very high risk did not achieve the stringent serum LDL-C target of <70 mg/dL. Patients receiving higher potency statins were significantly more likely to achieve LDL-C goals, whereas those with higher baseline LDL-C levels or Malaysian ethnicity were less likely to achieve LDL-C goals. CONCLUSIONS: Most CHD patients in the large group of Singapore residents with CHD in the present study did not achieve recommended LDL-C targets. A more effective disease-management approach, including patient education concerning lifestyle modification (e.g. diet, physical activity), efforts to enhance medication adherence, and more effective, well tolerated therapies such as high-equipotency or high-dose statins and statin combination regimens, may be needed to improve achievement of consensus cholesterol targets. This is the first study of cholesterol goal attainment in a large group of Southeast Asians and serves as a baseline for future evaluations in Asian populations.

Evaluation of lipid-lowering therapy and cholesterol goal attainment in Finland: the National FINRISK Study.

BACKGROUND: European and US study findings show that patients in primary care and specialty care are not adequately treated for cholesterol reduction. OBJECTIVE: To evaluate lipid-lowering treatment in Finland, estimate the proportions of subjects who are achieving cholesterol goals, and assess the influence of determinants on goal attainment. METHODS: Subgroup analysis of the FINRISK study, a national study of cardiovascular disease risk factors in Finland. Study participants, the subgroup of patients on lipid-lowering therapy from FINRISK, completed a postal self-administered questionnaire on health/health behavioral factors. Serum total cholesterol (TC) and other clinical variables were measured using a standardized protocol. Ten-year coronary risk was computed using Framingham risk equations. The influence of certain factors on goal attainment was determined by logistic regression analysis. The main outcome measure was the proportion of subjects who were receiving lipid-lowering therapy and achieved a TC goal of <5 mmol/L (<194 mg/dL). RESULTS: Among 9581 respondents, 622 subjects were on lipid-lowering therapy. Of these, 68 subjects were excluded because of missing data on TC and/or the type/dose of therapy. Among the 554 subjects included, 210 (38%) were secondary-prevention patients and 51% had 10-year coronary risk >/=20%. Approximately two-thirds of subjects were prescribed simvastatin (42%) or atorvastatin (26%), and about half (51%) were prescribed low-equipotency HMG-CoA reductase inhibitors (statins). There was no difference in equipotent doses of statins prescribed for primary and secondary prevention. About half (54%) of subjects did not attain their cholesterol goal (TC <5.0 mmol/L [194 mg/dL]). Subjects with coronary heart disease (odds ratio [OR] 3.00; 95% CI 2.07, 4.35) and patients prescribed medium-to-high equipotent statins (OR 1.93; 95% CI 1.35, 2.76) were more likely to achieve cholesterol goals, whereas postmenopausal women (OR 0.61; 95% CI 0.42, 0.88) were less likely than men to achieve cholesterol goals. CONCLUSION: Most (92%) patients receiving lipid-lowering therapy in a Finnish population were managed on statin monotherapy and approximately half of the patients did not achieve their recommended cholesterol goals. More effective and safe therapies are needed to enhance cholesterol goal attainment. These treatments might include regimens that act on two or more pharmacologic pathways.

Lipid management and cholesterol goal attainment in Norway.

OBJECTIVE: To document prescribing patterns of lipid-modifying therapies in hypercholesterolemic patients, cholesterol goal attainment, and factors associated with cholesterol goal attainment in Norway. METHOD: This was a retrospective, observational study using existing computerized patient records at 11 primary healthcare centers in Norway and the Norwegian Patient Register of hospital data. The study population was 3111 patients identified in the primary care database who were prescribed a lipid-modifying therapy between the dates of July 1987 and May 2003 and who were > or = 18 years of age at the time of the first prescription. Of these patients, 1337 patients had uncontrolled lipid measures at baseline. In the analysis of goal attainment, data were available for 877 (28% of the total study population) and 1144 (37%) patients with baseline and follow-up total cholesterol (TC) and/or low-density lipoprotein-cholesterol (LDL-C) levels after 4 and 12 months' treatment, respectively. OUTCOME MEASURES: Initial lipid-modifying therapy (drug and dosage), changes in initial lipid-modifying therapy, cholesterol goal attainment, and factors related to cholesterol goal attainment. Cholesterol treatment goals were defined as LDL-C <3.0 mmol/L and/or TC <5.0 mmol/L (as per the Second Joint Task Force of European Societies on the Prevention of Cardiovascular Disease). RESULTS: The initial lipid-modifying therapy was a HMG-CoA reductase inhibitor (statin) in 98% of patients, most often simvastatin (42%; mean initial dosage = 18.4 mg/day) or atorvastatin (34%; 12.7 mg/day). The median year of treatment initiation was 1999 and the mean duration of follow-up was 39 months. The initial prescription remained unchanged at year 1 for most patients (69%), whereas 17% discontinued drug treatment. Mean TC levels decreased from 7.36 mmol/L at baseline (n = 1337) to 5.31 mmol/L at 12 months (n = 1144; p < 0.05), whereas mean LDL-C levels decreased from 4.98 (n = 847) to 3.08 mmol/L at 12 months (n = 713; p < 0.05). These mean reductions occurred within 3 months of the initial prescription and did not change subsequently. A total of 32.9% of patients who were not at goal at baseline achieved cholesterol goal 12 months after initiating treatment. The factors related to cholesterol goal attainment at 12 months were: baseline TC level (odds ratio [OR] 0.64; 95% CI 0.58, 0.71), treatment with a statin (OR 8.60; 95% CI 1.13, 65.4), diagnosis of diabetes mellitus (OR 2.91; 95% CI 2.01, 4.21), and age (OR 1.02; 95% CI 1.01, 1.03). CONCLUSIONS: Lipid-modifying therapy in Norway is dominated by statin monotherapy. In this analysis of primary-care patients, maximal reductions in cholesterol levels were seen within the first 3-4 months after therapy initiation. After 12 months of treatment, 67% of patients remained above recommended cholesterol levels. More effective and well tolerated treatment strategies are needed to improve the probability of patients achieving cholesterol treatment goals.

Lipid-modifying therapy and attainment of cholesterol goals in Europe: the Return on Expenditure Achieved for Lipid Therapy (REALITY) study.

BACKGROUND: Few studies have been conducted in actual clinical practice settings to evaluate the ways in which dyslipidemia is managed using lipid-modifying therapies. OBJECTIVE: To determine lipid-modifying therapy practices and their effects on low-density lipoprotein cholesterol (LDL-C) and/or total cholesterol (TC) goal attainment in Europeans based on prevailing guidelines at the time of therapy in each country. METHODS: Retrospective cohort analysis involving 58,223 patients initiated on lipid-modifying therapies in 10 European countries, with a median patient follow-up on lipid-modifying therapy of 15.3 months. Data on prescriptions of lipid-modifying therapies, laboratory data including LDL-C and TC, achievement of cholesterol goals for LDL-C and/or TC, and hospitalizations were obtained from healthcare administrative databases and/or patient chart reviews. RESULTS: Across Europe, statin monotherapy was the initial lipid-modifying treatment in 51,786 (89.3%) of 58,009 patients with available data. In addition, 38,853 (89.5%) of 43,410 patients with available follow-up statin potency data were initiated on statin regimens of medium or lower equipotency. Low-equipotency regimens include atorvastatin 5 mg, simvastatin 10 mg, and pravastatin 20 mg, whereas medium-equipotency regimens include atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg. Regimens were adjusted to higher equipotency via either up-titration or switches to combination regimens in 16.2% of patients. On average, 40.5% of patients across Europe who were not initially at guideline recommended cholesterol goals (either LDL-C or TC) and had follow-up data attained recommended cholesterol levels, including <30% of patients in Spain, Italy, or Hungary. In many countries, the likelihood of goal attainment was inversely associated with baseline cardiovascular risk and/or LDL-C levels. CONCLUSIONS: Lipid management strategies in Europe during the study period were dominated by statin monotherapy. Even after prolonged follow-up on lipid-modifying therapy, approximately 60% of Europeans studied did not achieve guideline recommended cholesterol goals. Future emphasis must be placed on subsequent lipid panel monitoring, as well as the use of more efficacious, well-tolerated lipid-modifying therapies such as dual cholesterol inhibitors to enable more European patients to attain their recommended cholesterol goals.

Inappropriate initial treatment of secondary intra-abdominal infections leads to increased risk of clinical failure and costs.

AIMS: The objective of this population-based, retrospective cohort study was to investigate the incidence and initial antibiotic treatment of secondary intra-abdominal infections (sIAI) and to assess whether inappropriate initial antibiotic therapy affects patient outcomes. METHODS: All patients hospitalized for sIAI (1995-1998) were identified in the PHARMO Record Linkage System, a patient-centric database including pharmacy dispensing records from community pharmacies linked to hospitalization records in the Netherlands. Complementary in-hospital antibiotic drug use was obtained from the computerized inpatient pharmacy files. The patient outcomes considered were switch to second-line antibiotic treatment, re-operation, and death. In addition, a composite variable clinical failure was constructed based on the above-mentioned outcomes. Furthermore, the effect of clinical failure on length of hospital stay and costs of hospitalization was assessed. Associations between appropriateness of initial antibiotic treatment and outcomes were estimated using multivariate logistic and linear regression models. RESULTS: In the source population of 228,000 persons, 175 cases were classified as sIAI (mean age 49.3 +/- 24.5, 50.9% male) resulting in an incidence of 2.3/10,000 person-years [95% confidence interval (CI) 2.0, 2.7]. Initial antibiotic treatment was appropriate for 84% of the cases. The risk of clinical failure was 17.1%. Inappropriate initial antibiotic treatment increased the risk of clinical failure 3.4-fold (95% CI 1.3, 9.1). Length of hospital stay and costs of hospitalization were significantly increased for patients with clinical failure. CONCLUSIONS: Inappropriate choice of initial antibiotic therapy in sIAI patients leads to more clinical failure resulting in a longer hospital stay and higher costs of hospitalization compared with appropriate initial antibiotic therapy.

How appropriate is asthma therapy in general practice?

High association between burden of asthma and inadequate disease control make asthma management a major public health issue. We studied asthma management practices of general practitioners (GPs) in France to describe drug therapy and more specifically, to identify correlates of antibiotic prescriptions, a marker of inappropriate asthma management. Patients with persistent asthma aged 17-50 years were evaluated in a 12-month retrospective study using a computerized GPs database (Thales) and a patient survey, in which patients reported hospital contacts, use of oral corticosteroids and recent asthma symptoms. Therapy was described and the correlates of antibiotic prescriptions in the previous year were identified using multivariate logistic regression. During the study period, 16.4% of 1038 patients received one or more prescriptions of theophylline, 31.3% long-acting beta-agonists and 61.6% inhaled corticosteroids. Rates of prescription of antibiotics, expectorants, antihistamines, antitussives and nasal corticosteroids were 57.6, 42.0, 33.0, 19.9, and 14.4%, respectively. In parallel, 15% of patients reported at least one hospital contact for asthma and 43.1% used oral corticosteroids. Antibiotic prescriptions were more likely co-prescribed in patients using expectorants [odds ratio (OR) = 13.0, 95% confidence interval (CI) = 8.5-19.8] and antitussives (OR = 6.5, 95% CI = 3.7-11.6). Moreover, patients using courses of oral corticosteroids, and often visiting their GP (more than four times) during the study period were more likely to receive antibiotics. The results were unchanged when analyses were restricted to non-smokers and younger patients (< or = 40 years). Asthma management was sub-optimal among asthma patients treated by general practitioners in France. Antibiotics, expectorants, antihistamines, antitussives and nasal corticosteroids were commonly prescribed while asthma controllers were under-used.

Cost of care for patients treated with lipid-lowering drugs.

OBJECTIVE: To investigate the relationship between attainment of treatment goals with lipid-lowering therapy and healthcare costs. PARTICIPANTS: 9789 patients who received treatment with a lipid-lowering agent at any time between 1 January 1993 and 14 April 2003. DESIGN AND METHODS: A cohort study using linkage of patient medical records from 29 Swedish primary care centres and the Swedish national inpatient register. The primary outcomes of interest were the total costs of medical care and costs of cardiovascular-related inpatient care during the year before treatment initiation and during years 1, 2 and 3 of treatment. The cost data were analysed with a two-part random-effects regression model. RESULTS: Of the 9789 patients identified in the database for the study, 6316 had at least one cholesterol measurement during the year after the index prescription and were included in the analysis. 37% of the patients attained the goal of low-density lipoprotein cholesterol < 3.0 mmol/L and total cholesterol < 5.0 mmol/L. Patients who attained treatment goal had 44% higher pre-treatment costs of care. During the first year of treatment, patients who attained treatment goal had 28% higher costs of care. After the first year, costs for goal-attaining patients were 17% higher. However, the cost of cardiovascular-related inpatient care in patients attaining cholesterol treatment goal was twice as high as in patients not achieving goal before treatment start and 40% lower 2-3 years after treatment start. CONCLUSION: Patients reaching target cholesterol levels showed a trend of cost reductions over time, whereas no such trend could be found for patients not reaching goal levels. Reductions in costs were substantial for cardiovascular-related inpatient care for patients attaining cholesterol goals compared with patients not attaining cholesterol goals.

Development and validation of a model to project the long-term benefit and cost of alternative lipid-lowering strategies in patients with hypercholesterolaemia.

INTRODUCTION: Patients not currently reaching their lipid goals, even with the use of statins, are at elevated coronary heart disease (CHD) risk. Ezetimibe, when coadministered with a patient's current statin, has been shown to effectively reduce cholesterol in patients with hypercholesterolaemia. In order to help healthcare decision makers assess the cost effectiveness of this treatment strategy, a model is needed to compare ezetimibe coadministration versus alternative statin titration strategies among patients who have failed to reach their lipid goal with their current statin dose. METHODS: A flexible decision-analytic model that projects the long-term benefit and cost of alternative lipid-lowering strategies is described. Using a Markov process, the model allows movement from one health state to another based on the predicted risk of CHD events (fatal and nonfatal) and the risk of death from non-CHD causes. Each health state can be assigned a quality-of-life weight and an expected cost in order to determine the total survival time, quality-adjusted survival time and cost associated with the alternative treatment strategies. The accuracy of the model in projecting the percentage of patients who experience fatal and nonfatal CHD events was assessed by using individual baseline patient characteristics from two long-term outcomes trials: the Air Force Coronary Atherosclerosis Prevention Study, a primary prevention trial, and the Scandinavian Simvastatin Survival Study, a secondary prevention trial. RESULTS: Compared with event rates in the two outcome trials, the model appears to underestimate both the absolute risk of nonfatal CHD events and its reduction due to lipid lowering. But the model appears to provide reasonable estimates of the absolute reduction in fatal CHD events following lipid treatment. DISCUSSION: The model will allow one to assess the cost effectiveness of alternative treatment strategies for hypercholesterolaemia including statin titration and the coadministration of ezetimibe in patients who have failed to reach their lipid goal with a statin. Because the benefit of reducing nonfatal CHD events may be underestimated, the model may overestimate the cost-effectiveness ratio of ezetimibe coadministration.

Cost-effectiveness of ezetimibe coadministration in statin-treated patients not at cholesterol goal: application to Germany, Spain and Norway.

BACKGROUND: Despite the growing use of statins, many hypercholesterolaemic patients fail to reach their lipid goal and remain at elevated risk of coronary heart disease (CHD). Alternative treatment strategies, such as ezetimibe coadministration and statin titration, can help patients achieve greater lipid control, and thereby lower their CHD risk. But is it cost effective to more aggressively lower cholesterol levels across a broad range of current statin users? METHODS: Using a decision-analytic model based on epidemiological and clinical trials data, we project the lifetime benefit and cost of alternative lipid-lowering treatment strategies for CHD and non-CHD diabetic patients in Germany, Spain and Norway. RESULTS: It is projected that from 40% to 76% of these patients who have failed to reach their lipid goal with their current statin treatment will be able to reach their goal with ezetimibe coadministration; this represents a gain of up to an additional absolute 14% who will be able to reach their goal compared with a 'titrate to goal' strategy where patients are titrated in order to reach their lipid goal (up to the maximum approved dose). For CHD patients, the estimated incremental cost-effectiveness ratio for ezetimibe coadministration is under Euro 18 000 per life-year gained (Euro/LYG) and 26 000 Euro/LYG compared with strategies based on the observed titration rates and the aggressive 'titrate to goal' strategy, respectively; for non-CHD diabetic patients, these ratios are under 26 000 Euro/LYG and 48 000 Euro/LYG for ezetimibe coadministration compared with the two titration strategies. CONCLUSION: Compared with statin titration, ezetimibe coadministration is projected to be cost effective in the populations and countries studied.