Immunosuppression and the risk of readmission and mortality in patients with rheumatoid arthritis undergoing hip fracture, abdominopelvic and cardiac surgery.

OBJECTIVES: The impact of immunosuppression on postoperative outcomes has primarily been studied in patients undergoing joint replacement surgery. We aimed to evaluate the impact of biologics and glucocorticoids on outcomes after other major surgeries. METHODS: This retrospective cohort study used Medicare data 2006-2015 to identified adults with rheumatoid arthritis undergoing hip fracture repair, abdominopelvic surgery (cholecystectomy, hysterectomy, hernia, appendectomy, colectomy) or cardiac surgery (coronary artery bypass graft, mitral/aortic valve). Logistic regression with propensity-score-based inverse probability weighting compared 90-day mortality and 30-day readmission in patients receiving methotrexate (without a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD)), a tumour necrosis factor inhibitor (TNFi) or a non-TNFi biologic/tsDMARD <8 weeks before surgery. Similar analyses evaluated associations between glucocorticoids and outcomes. RESULTS: We identified 10 777 eligible surgeries: 3585 hip fracture, 5025 abdominopelvic and 2167 cardiac surgeries. Compared with patients receiving methotrexate, there was no increase in the risk of 90-day mortality or 30-day readmission among patients receiving a TNFi (mortality adjusted OR (aOR) 0.83 (0.67 to 1.02), readmission aOR 0.86 (0.75 to 0.993)) or non-TNFi biologic/tsDMARD (mortality aOR 0.78 (0.49 to 1.22), readmission aOR 1.02 (0.78 to 1.33)). Analyses stratified by surgery category were similar. Risk of mortality and readmission was higher with 5-10 mg/day of glucocorticoids (mortality aOR 1.41 (1.08 to 1.82), readmission aOR 1.26 (1.05 to 1.52)) or >10 mg/day (mortality aOR 1.64 (1.02 to 2.64), readmission aOR 1.60 (1.15 to 2.24)) versus no glucocorticoids, although results varied when stratifying by surgery category. CONCLUSIONS: Recent biologic or tsDMARD use was not associated with a greater risk of mortality or readmission after hip fracture, abdominopelvic or cardiac surgery compared with methotrexate. Higher dose glucocorticoids were associated with greater risk.

Quality of life in patients with advanced renal cell carcinoma treated with temsirolimus or interferon-alpha.

BACKGROUND: Temsirolimus was approved in Europe as first-line treatment of poor-prognosis advanced renal cell carcinoma (advRCC) based on significant clinical benefits. METHODS: Patients with advRCC and multiple poor-prognostic factors were randomly assigned to receive 25 mg intravenous temsirolimus weekly, interferon-alpha (titrated to 18 mU) three times weekly, or 15 mg intravenous temsirolimus weekly plus 6 mU of interferon-alpha three times weekly. EuroQol-5D utility score (EQ-5D index) and the EQ-5D visual analogue scale (EQ-VAS) responses were recorded. For analysis, patients were required to have their EQ-5D data recorded at baseline, week 12, and last visit after week 12. The analysis was conducted using last-visit data and a repeated-measures mixed-effect (RMME) model to evaluate quality-of-life differences between temsirolimus and interferon-alpha, controlling for baseline covariates. RESULTS: Average EQ-5D score at the last measure was significantly higher in patients receiving temsirolimus compared with interferon-alpha: by 0.10 on EQ-5D index (P=0.0279) and by 6.61 on EQ-VAS (P=0.0095). In the RMME model, the least-square mean for on-treatment EQ-5D index score was 0.590 with temsirolimus and 0.492 with interferon-alpha (P=0.0022). CONCLUSION: Temsirolimus is associated with significantly higher EQ-5D scores compared with interferon-alpha in patients with previously untreated poor-prognosis advRCC.

Development of a diabetes treatment simulation model: with application to assessing alternative treatment intensification strategies on survival and diabetes-related complications.

AIMS: The objective of this analysis is to project the long-term impacts on life expectancy and occurrence over 5, 10, and 40 years of microvascular and macrovascular complications of diabetes when using different haemoglobin A1c (HbA1c) thresholds for intensifying treatment of type 2 diabetes. METHODS: A flexible, discrete-event simulation model has been developed to evaluate alternative treatment strategies based on the United Kingdom Prospective Diabetes Study Outcomes Model. In the present analysis, the model is used to investigate the impact of alternative HbA1c thresholds for treatment intensification ranging from 7.0 to 9.0%. For each intensification strategy, the model is run using 80 simulated patients for each of 1224 patient profiles from the Real-Life Effectiveness and Care Patterns of Diabetes Management study (for a total of 97,920 simulated patients) to project the number of patients who will experience diabetes-related complications over time. RESULTS: The use of lower HbA1c thresholds for intensifying treatment is associated with improved long-term outcomes. When the HbA1c threshold for intensifying therapy from oral treatment to basal insulin (T1) is 7.0% and the threshold for intensifying basal insulin to multiple-dose insulin (T2) is 7.0%, simulated patients spend 54% of their time with HbA1c >7.0%, but 95% of their time with HbA1c >7.0% if T1 and T2 are set to 9.0%. More aggressive or proactive treatment postures are projected to reduce clinical events, including diabetes-related deaths and diabetes-related complications, particularly myocardial infarctions (MIs). When T1 and T2 are set to 7.0%, there are 592 fewer diabetes-related deaths in the first 5 years of the simulation and 3740 fewer deaths over 40 years compared with the results when T1 and T2 are set to 9.0%. These decreases in deaths were also associated with a 0.35 year gain in projected life expectancy. Compared with an aggressive strategy with both T1 and T2 being 7%, 644 more patients are projected to experience at least one episode of MI in the first 5 years if treatment intensification is delayed until HbA1c reaches 9.0%. This number increases over time, reaching 2906 additional patients experiencing at least one MI over a 40-year time period. CONCLUSIONS: We report results from a discrete-event simulation model to explore the impact of alternative treatment strategies for patients with type 2 diabetes. Strategies that intensify therapy (in response to rising HbA1c levels) at lower HbA1c thresholds (e.g. 7.0%) are associated with enhanced projected long-term health outcomes.

Glycaemic control among patients with type 2 diabetes mellitus in seven European countries: findings from the Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) study.

OBJECTIVE: This study was undertaken to assess glycaemic control as well as changes in glycaemic control over time in patients with type 2 diabetes mellitus (T2DM) who added a sulphonylurea (SU) or thiazolidinedione (TZD) to their metformin monotherapy in typical treatment settings within seven European countries. METHODS: An observational, cross-sectional multicentre study with retrospective medical chart review was conducted in Finland, France, Germany, Norway, Poland, Spain and UK. T2DM patients who added a SU or a TZD to metformin monotherapy between January 2001 and January 2006 (i.e. index date) and who had > or = 1 haemoglobin A1C (HbA1C) measurement within 12 months before the visit date, which occurred from June 2006 to February 2007, were included in the study. Demographic and clinical data were collected from medical records. The main study outcome measure was the proportion of patients with adequate glycaemic control (defined according to the International Diabetes Federation as HbA1C < 6.5%) using the most recent HbA1C measurement before the visit date. In addition, patients were grouped based upon the interval from the index date to the most recent HbA1C measurement to evaluate goal attainment and treatment changes over time. FINDINGS: In this European cohort of 2023 T2DM patients on metformin and either an SU or a TZD (mean age = 60.4 years), 25.5% of patients had adequate glycaemic control. The average HbA1C level was 7.2% after a mean of 2.6 years of treatment with combination oral antihyperglycaemic agent (AHA) therapy. Among the patients (n = 227) with most recent HbA1C measurement within 1 year after first adding an SU or a TZD, 27% had adequate glycaemic control (HbA1C < 6.5%), with a mean (s.d.) HbA1C of 7.1% (1.0); 1.3% of these patients were using some type of insulin therapy. Among the patients (n = 176) with most recent HbA1C measurement occurring > or = 5 years after adding an SU or a TZD, 20% had adequate glycaemic control, with a mean (s.d.) HbA1C of 7.4% (1.17), and 29.6% of these patients were using insulin. Overall, patients with (vs. without) adequate glycaemic control had significantly (p < 0.05) lower HbA1C levels (7.6 vs. 8.2%) at the time of adding an SU or a TZD to ongoing metformin monotherapy, were less likely to report a history of macrovascular complications (20 vs. 26%) and were more often engaged in physical activity three to five times a week (29 vs. 23%). CONCLUSIONS: Approximately one quarter of European out-patients with T2DM had adequate glycaemic control after a mean of 2.6 years following initiation of combination AHA therapy. Overall glycaemic control modestly declined over time, even though more patients were being treated with insulin. These findings highlight the progressive nature of the disease and need for more effective disease management/therapeutic alternatives.

Cost-effectiveness of sitagliptin-based treatment regimens in European patients with type 2 diabetes and haemoglobin A1c above target on metformin monotherapy.

OBJECTIVE: Sitagliptin is a novel oral incretin enhancer that acts by inhibiting the dipeptidyl peptidase 4 enzyme and is indicated in Europe as a treatment adjunct to metformin (MF), sulphonylurea (SU), MF plus SU and diet and exercise, in the management of type 2 diabetes mellitus. The objective of the current analysis was to evaluate the cost-effectiveness of adding sitagliptin to the regimens of patients with haemoglobin A1c (HbA1C) above the International Diabetes Federation goal (6.5%) while on MF in six European countries: Austria, Finland, Portugal, Scotland (United Kingdom), Spain and Sweden. METHODS: A discrete event simulation model, which employed the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model risk equations for predicting risks of diabetes-related complication, was used. Lifetime costs and benefits were projected for alternative treatment strategies of adding sitagliptin, compared with adding rosiglitazone or a SU to MF in patients not at HbA1C goal on MF monotherapy. Changes in HbA1C as well as side effects associated with these different treatment strategies were based on clinical trial data. Mean baseline values from local epidemiologic studies involving patients with type 2 diabetes not at HbA1C goal on MF monotherapy were included in the current analysis. Costs of medications, side effects and direct costs of diabetes-related complications were based on country-specific data. UKPDS-based disutility weights associated with diabetes complications were incorporated. Disutilities associated with medication side effects were based on published data. All future costs and benefits were discounted according to local guidelines on cost-effectiveness analysis. One-way sensitivity analyses were conducted by varying key input parameters. FINDINGS: The discounted incremental cost-effectiveness ratios (ICER) associated with the addition of sitagliptin to MF, compared with adding rosiglitazone, in the different countries analysed ranged from treatment with sitagliptin being dominant (cost saving with improved health outcome) to its being cost-effective [4,766 euros per quality-adjusted life year (QALY)]. Treatment with sitagliptin added to MF was cost-effective compared with adding a SU, with discounted ICER values ranging from 5949 euros/QALY to 20,350 euros/QALY across countries. Sensitivity analyses showed that these results were robust to changes in input parameters, including clinical efficacy, costs and utility weights for both diabetes-related complications and hypoglycaemia. CONCLUSIONS: Compared with adding rosiglitazone or a SU to MF, adding sitagliptin to MF is projected to be either cost saving or cost-effective for patients with type 2 diabetes who are not at HbA1C goal on MF.

Long-term achievement of the therapeutic objectives of lipid-lowering agents in primary prevention patients and cardiovascular outcomes: an observational study.

AIMS: Lowering elevated cholesterol levels reduces cardiovascular (CV) morbidity and mortality. Nonetheless, most patients treated with lipid-lowering agents (LLA) do not reach recommended therapeutic objectives. In a setting of primary care in France, we investigated the association between LDL-cholesterol goal attainment and the occurrence of CV events in primary prevention patients with multiple CV risk factors (> or = 3). According to national guidelines, the therapeutic objective (TO) for such patients is an LDL-cholesterol value below 130 mg/dL. METHODS: 579 patients treated with LLA and with LDL-cholesterol values documented at least once a year over a period of at least 3 years (2000-2002) were allocated to three groups based on the number of years the TO was attained during the follow-up period: in all 3 years (TO+++: n=145), only part of the time (TO intermediate: n=256), and never (TO---: n=178). CV events (angina pectoris, myocardial infarction, heart failure, stroke, peripheral artery disease) occurring during the last year of observation (2002) were retrospectively collected. The occurrence risk (OR) of CV events was assessed based on TO status, with a logistic regression model to adjust for baseline differences in CV risk factors. RESULTS: Only a quarter of patients attained TO during all 3 study years. CV events during the third year of observation occurred in 5.5%, 10.5% and 12.9% of patients in the TO+++, TO intermediate and TO--- groups, respectively. Compared with TO+++ patients, the risk of CV events increased significantly in TO intermediate (OR=2.34, 95% CI=[1.01-5.39]) and TO--- patients (OR=2.99, 95% CI=[1.26-7.08]). CONCLUSION: In real practice, a prolonged attainment of TO is rarely observed in high CV risk patients treated with LLA as primary prevention. Therapeutic failure is related to an increased incidence of cardiovascular morbidity. Our data strongly support the need to improve adherence to treatment guidelines to achieve effective cardiovascular prevention.

Current lipid management and low cholesterol goal attainment in common daily practice in Spain. The REALITY Study.

OBJECTIVE: To evaluate prescribing patterns of lipid-lowering drugs used in management of patients at risk of coronary heart disease (CHD) in usual clinical practice in Spain and to assess low-density lipoprotein cholesterol (LDL-C) goal attainment among CHD and CHD equivalent patients (< 100 mg/dL) and non-CHD patients with two or more risk factors (< 130 mg/dL) who were prescribed lipid-lowering drugs. METHODS: Cohort study with retrospective chart review at 23 primary care centres and 16 lipid treatment centres across Spain (59% primary care; 41% outpatient lipid centres). Physicians consecutively identified eligible patients. Adults (aged > or = 18 years) with CHD/CHD equivalent or two or more major risk factors prior to first prescription of lipid-lowering drugs were eligible. Medical records were reviewed by physicians to collect patient characteristics, baseline and follow-up laboratory values and lipid-lowering drug treatment data. RESULTS: 619 patients (45.5% CHD and CHD equivalent patients and 54.5% non-CHD with two or more major risk factors) were included in the study with an average study follow-up of 3.6 years. Mean age was 60.1 years (SD 10.2), and 47.8% were female. Mean baseline LDL-C was 178 mg/dL (SD 45.0) for the CHD/CHD equivalent patients and 191 mg/dL (SD 56.95) for patients with two or more risk factors. Statins were the initial lipid-lowering drugs in 90.2% of patients; 52.5% of patients were initiated on low-dose (simvastatin 10mg or lower potency) statins. Overall 20.2% of CHD/CHD equivalent and 31.4% of patients with two or more risk factors attained LDL-C goal during the study period; of patients not attaining goal, 28.7% required an additional LDL-C reduction of > 30% to attain goal. In a logistic regression model for goal attainment, CHD/CHD equivalent patients (odds ratio [OR] 0.47; 95% confidence interval [CI] 0.31, 0.72) and patients with baseline LDL-C > 190 mg/dL (OR 0.53; 95% CI 0.35, 0.80) were least likely to reach cholesterol goal when compared with patients having baseline LDL-C > 100 mg/dL and < 130 mg/dL. CONCLUSION: Only 12.9% of patients attained LDL-C goal on their initial lipid-lowering drugs, and an additional 13.4% achieved goal after a change in their lipid-lowering therapy, resulting in 73.7% of patients not attaining goal after at least 3 years of follow-up, after initiation of lipid-lowering therapy. Patients who would gain the most from aggressive lipid lowering (CHD patients and patients with high baseline LDL-C) were least likely to achieve goal. More effective lipid management is needed to help these patients lower their cholesterol to goal levels or even lower.

Determinants of cholesterol goal attainment at 12 months in patients with hypercholesterolaemia not at consensus goal after 3 months of treatment with lipid-lowering drugs.

BACKGROUND: Less than half of patients in Scandinavian societies achieve target cholesterol values established by consensus coronary prevention panels. METHODS AND RESULTS: Using logistic regression analysis, we determined that patients not at consensus cholesterol goals after 3 months of treatment using lipid-lowering medications were significantly more likely to achieve these goals at 12 months if they were treated with an active management strategy (changes in lipid-lowering therapy within 3 months), had a diagnosis of diabetes mellitus, or initiated lipid-lowering more recently, compared with their counterparts without these factors. CONCLUSION: An active management strategy is associated with a higher probability of achieving treatment goals in patients not at goal after 3 months following treatment initiation.

Ineffectiveness of lipid-lowering therapy in primary care.

BACKGROUND: Evidence confirms the positive effects of lipid-lowering agents on the risk of cardiovascular disease. Local guidelines in France (AFSSAPS) have defined therapeutic objectives for LDL-cholesterol. These objectives vary with the number of cardiovascular risk factors in addition to dyslipidaemia. We determined the proportions of patients at therapeutic objective in different classes of cardiovascular risk to test the hypothesis that compliance with guidelines varies across the levels of risk. Comparison with international guidelines (ANDEM) was also performed. METHODS: A group of 3173 dyslipidaemic patients treated with lipid-lowering agents and managed by general practitioners was randomly selected from BKL-Thales panel, a French computerized database. For each patient, history of coronary heart disease and the number of cardiovascular risk factors were documented. Compliance with guidelines was assessed from achievement of therapeutic objective. RESULTS: The study population included 79% primary prevention patients (1.6, 25.5, 31.7 and 20.1%, with 1, 2, 3, and >3 risk factors, respectively) and 21.0% secondary prevention patients. Applying AFSSAPS guidelines, the proportions of primary prevention patients not at LDL-cholesterol objectives varied across risk categories (P < 0.0001), from 3.9% for patients with one risk factor to 46.5% for patients with >3 risk factors, and therapeutic failure reached 39.9% in secondary prevention. Only 26% of patients who were at high cardiovascular risk (>3 risk factors or prior coronary heart disease) and not at therapeutic objective received high doses (>standard recommended doses) of lipid-lowering agents in monotherapy. Applying ANDEM guidelines, 74% of secondary prevention patients were not at treatment goal. CONCLUSION: Compliance with guidelines varied inversely with the level of cardiovascular risk. Besides, most patients not at therapeutic objective were not up-titrated. The use of lipid-lowering agents is inadequate, depriving many patients of an effective protection against cardiovascular diseases.