Deep Vein Thrombosis in Europe-Health-Related Quality of Life and Mortality.

OBJECTIVES: Deep vein thrombosis (DVT) is a major health-care burden in Europe, but exact estimates are lacking. This study reports results from the PREFER venous thromboembolism (VTE) study concerning health-related quality of life (HrQoL) and mortality of patients with DVT. METHODS: PREFER VTE was a prospective, observational study, conducted in 7 European countries, designed to provide data concerning treatment patterns, resource utilization, mortality, and QoL. First-time or recurrent patients with DVT were followed at 1, 3, 6, and 12 months. Health-related QoL-as measured by the EuroQoL 5-Dimension 5-Level instrument ( EQ-5D-5L)-was analyzed using Tobit regression with repeated measures, assessing the impact of baseline characteristics stratified by cancer activity. Mortality was analyzed using logistic regression. RESULTS: At baseline, patients with DVT had a 0.14 lower EQ-5D-5L index score (0.72 for total sample) compared to the reference UK population (0.85). The EQ-5D-5L index score improved from baseline to 12 months in patients with active cancer (from 0.70 to 0.79) and those without (0.72-0.87); 7.3% died within a year, a 5.2% excess mortality compared to the age- and gender-adfjusted general population. The 12-month mortality rate of DVT varied between 2.9% in the pooled data from Germany, Switzerland, or Austria and 15.4% in Italy. Furthermore, the mortality rate differed between patients with active cancer and those without (42.9% vs 4.7%). CONCLUSIONS: Deep vein thrombosis is associated with a substantial burden of illness in terms of HrQoL at baseline, which following treatment normalizes after 12 months and has a significant mortality rate. In addition, active cancer has a significant impact on mortality and the HrQoL of patients with DVT.

[Hypercholesterolemia - Where are we today? Where are we going?]. / Hypercholesterinämie - Wo stehen wir heute? Wo wollen wir hin?

Hypercholesterolemia is one of the major modifiable risk factors for the development of atherosclerosis. Increasing LDL cholesterol is associated with an increased risk of developing cardiovascular diseases as well as cardiovascular ischemic complications. Studies with statins and ultimately with ezetimibe have been able to impressively demonstrate that lowering LDL cholesterol contributes to a significant reduction of cardiovascular ischemic complications.Based on the results of randomized trials for lipid lowering, the practice guidelines developed by the professional societies have defined LDL cholesterol goals. High-risk patients, such as patients with clinically manifest cardiovascular disease, type 2 diabetes, type 1 diabetes with organ damage, moderate or severe chronic kidney disease or a risk of SCORE ≥10 %, should reach LDL cholesterol values <70 mg/dl. Data from observational trials demonstrated that in daily practice only about 20 % of treated high-risk patients reached this recommended LDL cholesterol goal. The therapeutic options are not yet exhausted; patients are treated mainly with low or at most average statin dosages. There should be more potent and high-dose statins used as well as the combination therapy of statin and ezetimibe to achieve the recommended LDL cholesterol goals. Specific cardiac rehabilitation and prevention programs with regular benchmarking could support improved goal-achievement. The new therapeutic option of PCSK9 inhibitors, which significantly and safely lower LDL cholesterol on top of statins and ezetimibe, is currently investigated in large randomized outcome trials.

Impact of body weight on antidiabetic treatment and predictors of weight control under real-world conditions: a 2-year follow-up of DiaRegis cohort.

AIMS: Treatment strategies for obese patients with type 2 diabetes mellitus aim to increase physical activity, reduce body weight, and improve glucose control using weight-beneficial antidiabetic drugs. The objective of this study was to determine whether these strategies are implemented, and to identify factors predictive of glucose control and body weight management in a large, real-world patient population. METHODS: The prospective DiaRegis cohort study included 3807 patients with type 2 diabetes in whom the treating physician decided to intensify and optimize treatment because of insufficient glucose control. RESULTS: Antidiabetic treatment of overweight and obese patients was compared with that of normal-weight patients over a 2-years follow-up period, and multivariate analyses were performed to identify predictors of body weight loss. Among the 3807 participants, 92.5 % were overweight or obese. Normal-weight participants were more often treated with sulfonylureas or insulin, and overweight and obese patients with metformin or glucagon-like peptide (GLP)-1 analogues. Predictors of weight loss were body mass index (BMI) ≥30 kg/m(2) and any reported physical activity. CONCLUSIONS: DiaRegis study shows that under real-world conditions, antidiabetic drug therapy is performed dependent on body weight. This strategy results in adequate glucose control and moderate weight reductions in overweight and obese patients. Weight loss is affected by treatment with weight-beneficial drugs, but also by any reported physical activity. However, only a small subgroup of patients perform physical activity. Initiation and maintenance of a physically active lifestyle remains a significant challenge for physicians, and patients with type 2 diabetes.

[Antithrombotic treatment in patients with stable coronary artery disease. Which drugs and for how long?]. / Antithrombozytäre Therapie bei stabiler KHK. Was, wie lange?

Stable chronic coronary artery disease (SCAD) encompasses several groups of patients including those with stable angina pectoris or other symptoms thought to be linked to CAD as well as patients with known prior acute coronary syndrome or prior coronary interventions, who have become asymptomatic with treatment and need regular follow-up. Patients with SCAD have an elevated risk for subsequent ischemic events and significantly benefit not only from lipid-lowering therapy with statins but also in particular from long-term antithrombotic treatment. These patients therefore need lifelong antithrombotic treatment with 100 mg acetylsalicylic acid (ASA) daily whereby clopidogrel 75 mg daily is indicated as an alternative in cases of aspirin intolerance. As chronic CAD may present with very different developmental phases spanning from chronic stable phases to acute coronary syndromes, antithrombotic treatment in SCAD patients needs continuous evaluation and adaptation. In addition, new concomitant diseases, such as atrial fibrillation may necessitate further adaptation of antithrombotic therapy. The current overview focuses on the description of the long-term antithrombotic treatment of SCAD as well as on the need for adaptation in the setting of elective percutaneous coronary interventions (PCI).

Prognostic implications of DPP-4 inhibitor vs. sulfonylurea use on top of metformin in a real world setting - results of the 1 year follow-up of the prospective DiaRegis registry.

BACKGROUND: DPP-4 inhibitors (DPP4-I) have been shown to provide non-inferior glycaemic control compared with sulfonylureas (SU), but result in a reduction of body weight and a significantly lower risk of hypoglycaemia in patients with type 2 diabetes. We aimed to validate these results in a large real-world sample of patients participating in the prospective DiaRegis registry and to assess prognostic implications. METHODS: DiaRegis included 3810 patients with type 2 diabetes in which antidiabetic therapy was intensified. We defined two patient subgroups, the first receiving either a DPP4-I or SU on top of prior metformin monotherapy and the second containing patients out of subgroup 1 with unaltered treatment for 1 year. RESULTS: After enrolment 884 patients with prior metformin monotherapy received a dual combination of metformin with either DPP4-I (n = 628; 71%) or SU (n = 256; 29%). Patient characteristics, blood glucose and blood pressure control as well as comorbidity burden were virtually identical. There were neither significant differences in the change of HbA1c over the 12 months treatment period nor in the reduction of body weight, but fasting (p = 0.033) and postprandial glucose levels (p = 0.01) were significantly lower in those receiving DPP4-I. Hypoglycaemia was significantly less frequent in patients receiving DPP4-I (OR 0.32; 95% CI 0.19-0.54). Qualitative changes were robust for subgroup 2 (except of fasting plasma glucose). Patients receiving DPP4-I had significantly less stroke/transitory ischaemic attack (0.2 vs. 2.0; p < 0.05) during the 1 year follow-up, whereas other vascular events (coronary artery bypass graft, percutaneous coronary intervention) were borderline significant. CONCLUSIONS: The present results confirm prior randomised controlled trial results in patients with type 2 diabetes from real world clinical practice demonstrating that DPP4-I on top of prior metformin monotherapy result in similar HbA1c reductions within 12 months but a significant reduction in hypoglycaemia compared with sulfonylurea added to metformin. The reduction in vascular events observed has to be verified in larger cohorts.

[Lipid therapy in daily routine]. / Lipidtherapie im Alltag.

Patients with increased cardiovascular risk profile are frequently seen in general practice. Comprehensive management of modifiable risk factors, in particular dyslipidemia, is mandatory. Many studies in clinical practice have shown a gap between the recommendations in clinical guidelines and the actual situation. Current data on the management situation of patients with high cardiovascular risk is provided by the prospective registry LIMA. Primary care physicians in 2,387 offices throughout Germany documented 13,924 patients with coronary artery disease (CAD), diabetes mellitus or peripheral arterial disease (PAD). Treatment with simvastatin 40 mg was an inclusion criterion. Physicians documented drug utilization, laboratory values (lipids, blood glucose), blood pressure and clinical events over one year and received feedback about the target value attainment of their patients after data entry. Mean age of the patients was 65.7 years, and 61.6 % were men. CAD was reported in 70.6 %, diabetes mellitus in 58.2 % and PAD in 14.9 %. Most patients (68 %) received simvastatin as monotherapy also after the inclusion visit; 20.6 % of patients received in addition the cholesterol absorption inhibitor (ezetimibe) in the first 6 months, and 23.3 % in the second 6 months. Patients achieved the LDL-cholesterol target value in 31.8 % at entry and 50.0 % after one year. The blood pressure target < 140 /90 mmHg was reached by 65.8 % after one year. Of patients with diabetes mellitus 40.0 % reached an HbA1c value below 6.5 %. Clinical events (death, hospitalization, (cardio-) vascular events, and dialysis) were reported by 11.7 % of patients between entry and Month 6, and by 12.0 % between Month 7 and 12. In daily practice comprehensive management of risk factors in patients at high cardiovascular risk remains a challenge. For normalization of increased LDL cholesterol values addition of ezetimibe to existing statin therapy improves the chances of patients for target level attainment.

[Comorbidity, hypoglycaemia and appropriate selection of antidiabetic pharmacotherapy in diabetic patients with heart failure in clinical practice in Germany. Results of the DiaRegis registry].

BACKGROUND: Patients with type 2 diabetes and heart failure are considered to be at high risk for hypoglycaemic complications. There is a considerable uncertainty with respect to the appropriate choice of antidiabetic pharmacotherapy in patients with type 2 diabetes and comorbid heart failure. Little is known about comorbidity, hypoglycaemia rates and selected pharmacotherapy in diabetic patients with heart failure in clinical practice. METHODS: DiaRegis is a prospective registry in Germany including 3,810 patients with type 2 diabetes receiving antidiabetic treatment with oral mono or oral dual combination therapy in 2009/2010. Only patients for which adjustment of pharmacotherapy (including the introduction of insulin and GLP-1 analogues) was deemed necessary were enrolled. We examined the differences in comorbidity, hypoglycaemia and choice of anti-diabetic pharmacotherapy between diabetics with and without clinical heart failure in clinical practice in Germany. RESULTS: For 3,746 patients, data on the presence of heart failure were available, median (IQR) age 65.9 (57.6-72.8) years and 46.8% were female. Patients with heart failure (n = 370; 9.9%) were older, had a higher BMI, were less physically active, and had more cardiovascular risk factors and a substantial comorbidity. Glycaemic control was comparable between groups. Of the patients with heart failure, 76.8% received metformin, 32.7% sulfonylureas, 2.2% glucosidase inhibitors, 4.3% glinides, 6.2% glitazones and 7.3% DPP-4 inhibitors at baseline before adjustment of therapy. In multivariate analyses, patients with heart failure received less metformin (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.43-0.79) and sulfonylureas (OR 0.70, 95%CI 0.52-0.95) but not thiazolidinediones (OR 1.22, 95%CI 0.82-1.81) or other antidiabetic drugs. Hypoglycaemia was considerably more frequent in diabetic patients with heart failure than in those without (OR 1.96, 95%CI 1.47-2.61). CONCLUSION: Patients with type 2 diabetes and heart failure had a substantially increased comorbidity burden compared to patients without heart failure. They more often suffered from episodes of hypoglycaemia, especially those requiring medical assistance. The diagnosis of heart failure did not impact the choice of antidiabetic pharmacotherapy in patients with type 2 diabetes. There was no differential use of thiazolidinediones despite evidence discouraging their use in patients with heart failure.

[Diabetes and heart failure: a practically oriented critical appraisal]. / Diabetes und Herzinsuffizienz: eine praxisorientierte, kritische Bestandsaufnahme.

Patients with type 2 diabetes have an increased risk for developing symptoms of heart failure. These can be accompanied by a reduction of left ventricular ejection fraction (HFREF, systolic heart failure) or by a preserved function (HFPEF, diastolic heart failure). The pathophysiology of both entities is distinct and involves impairment of myocardial metabolism and coronary circulation alike. Although diabetes and heart failure often coincide, the management of these patients particularly with respect to the specific benefits or possible hazards of antidiabetic treatment is vague. Therefore, from a pathophysiological as well as clinical viewpoint, 1) diabetic patients with symptoms of heart failure have to be differentiated regarding systolic as well as diastolic left ventricular function by echocardiography and tissue doppler imaging. 2) Heart failure in diabetic patients needs similar attention due to a prognosis and interactions. 3) Optimized blood glucose lowering in combination with improvement of other cardiovascular risk factors is evident for HFREF and is assumed to be beneficial for HFPEF. 4) Antidiabetic medication has to be specifically adapted for both entities. As prospective, controlled studies are scarce, future interventional studies should specifically focus on clinical outcome in diabetic patients with different entities of heart failure.

Persistent lipid abnormalities in statin-treated patients with diabetes mellitus in Europe and Canada: results of the Dyslipidaemia International Study.

AIM: To assess the prevalence of persistent lipid abnormalities in statin-treated patients with diabetes with and without the metabolic syndrome. METHODS: This was a cross-sectional study of 22,063 statin-treated outpatients consecutively recruited by clinicians in Canada and 11 European countries. Patient cardiovascular risk factors, risk level, lipid measurements and lipid-modifying medication regimens were recorded. RESULTS: Of the 20,129 subjects who had documented diabetes and/or metabolic syndrome status, 41% had diabetes (of whom 86.8% also had the metabolic syndrome). Of those with diabetes, 48.1% were not at total cholesterol target compared with 58% of those without diabetes. Amongst those with diabetes, 41.6 and 41.3% of those with and without the metabolic syndrome, respectively, were not at their LDL cholesterol goal relative to 54.2% of those with metabolic syndrome and without diabetes, and 52% of those with neither condition. Twenty per cent of people with diabetes but without the metabolic syndrome were not at the optimal HDL cholesterol level compared with 9% of those with neither condition. Of people with diabetes and the metabolic syndrome, 49.9% were not at optimal triglyceride level relative to 13.5% of people with neither diabetes nor the metabolic syndrome. Simvastatin was the most commonly prescribed statin (>45%) and the most common statin potency was 20-40 mg/day (simvastatin equivalent). Approximately 14% of patients were taking ezetimibe alone or in combination with a statin. CONCLUSIONS: Despite evidence supporting the benefits of lipid modification and international guideline recommendations, statin-treated patients with diabetes had a high prevalence of persistent lipid abnormalities. There is frequently room to optimize therapy through statin dose up-titration and/or addition of other lipid-modifying therapies.

[Regional differences in the treatment of dyslipidemia in Germany]. / Regionale Unterschiede in der Behandlung von Fettstoffwechselstörungen innerhalb Deutschlands?

BACKGROUND AND OBJECTIVE: DYSIS (Dyslipidemia International Study) is an international multicenter cross-sectional trial. The objective of the regional analysis was to identify differences in lipid-lowering therapy and attainment of goal/normal lipid levels in Germany. METHODS: 4,260 patients who were at least 45 years of age and receiving regular statin therapy at 748 centers (office practices / outpatient clinics) in Germany were assessed at a routine ambulant appointment. Results from centers in the northern, eastern, southern, and western part of Germany were compared. RESULTS: The mean age of the patients was 66.6 - 67.9 years (p < 0.01, range over the four regions) and the proportion of males was 53 - 60 % (p < 0.01). There were significant regional differences in the number of cardiovascular risk factors and cardiovascular conditions, e. g. arterial hypertension (82 - 88 %), smoking (12 - 17 %), family history of coronary heart disease (CHD) (30 - 42 %), lack of exercise (38 - 48 %), CHD (only in women, 27 - 42 %), peripheral artery vascular disease (11 - 15 %), and heart failure (16 - 20 %). No regional differences were found for body mass index (BMI), waist circumference, metabolic syndrome, or diabetes mellitus. The mean LDL-cholesterol level in the four regions was 107 - 108 mg/dl (p = 0.53), HDL-cholesterol was 50 - 51 mg/dl (p = 0.62), and triglycerides 141 - 148 mg/dl (p = 0.68). The mean simvastatin (or simvastatin-equivalent) dosage was approximately 27 mg/day (p = 0.62). About half of the patients (49 - 53 %, p = 0.11) failed to attain their LDL-cholesterol target despite statin therapy. In addition to elevated LDL-cholesterol, 30 % of the patients had elevated triglycerides and/or low HDL-cholesterol. CONCLUSION: DYSIS showed the existence of significant regional differences in the characteristics of statin-treated patients but not in the type or dosage of statin therapy or in adherence to target/normal lipid levels as per guidelines. In a high proportion of patients the lipid-lowering therapy will need to be reviewed, as guideline target levels have not been attained.

Beneficial effects of abciximab in patients with primary percutaneous intervention for acute ST segment elevation myocardial infarction in clinical practice.

OBJECTIVES: To assess the safety and effectiveness of abciximab in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) in clinical practice. METHODS: Data were analysed of 2184 consecutive patients treated with primary PCI for acute STEMI and either concomitant abciximab or no glycoprotein IIb/IIIa inhibitor (control group), who were prospectively enrolled in the Acute Coronary Syndromes (ACOS) registry between July 2000 and November 2002. RESULTS: Patients who were treated with abciximab were younger than the control group, and fewer of them had a history of stroke/transient ischaemic attack and systemic hypertension, but more of them had three-vessel coronary artery disease and cardiogenic shock. Cumulated mid-term survival for patients treated with abciximab was significantly higher than in the control group (91% v 79%, log rank p < 0.05, median observational time 375 days, range 12-34 months). The Cox proportional hazards model of mid-term mortality after admission with adjustment for baseline characteristics showed that mortality was significantly lower in the abciximab group than in the control group (hazard ratio 0.68, 95% confidence interval 0.49 to 0.95). Whereas overall there was no difference in bleeding complications, patients older than 75 years had more major bleeding events with abciximab (12.5% v 3.4%, p = 0.03). CONCLUSION: In clinical practice adjunctive treatment with abciximab in patients with primary PCI for acute STEMI was associated with a reduction in mid-term mortality. The subgroup of patients older than 75 years who were treated with abciximab had more major bleeding complications.

Which factors are associated with the application of reperfusion therapy in ST-elevation acute coronary syndromes?. Lessons from the Euro Heart Survey on Acute Coronary Syndromes I.

BACKGROUND/AIMS: A large proportion of patients with a ST-elevation acute coronary syndrome do not receive reperfusion therapy. In order to contribute to a better understanding of the clinical decision making process, we analyzed which factors are associated with the application of reperfusion therapy. METHODS: From the Euro Heart Survey of Acute Coronary Syndromes I, 4,260 patients with ST-elevation acute coronary syndrome were selected for the current analysis, of which 1,539 (36%) patients received fibrinolysis and 904 (21%) primary percutaneous coronary intervention (PCI). The analysis contained 32 variables on demographics, medical history, admission parameters and reperfusion therapy. RESULTS: A short pre-hospital delay, arrival in a hospital with PCI facilities, severe ST-elevation, and participation in a clinical trial were the strongest predictors for receiving reperfusion therapy. Primary PCI was more likely to be performed than fibrinolysis in patients with a long pre-hospital delay, arriving in a hospital with PCI facilities, not participating in a clinical trial, and with at least one previous PCI. CONCLUSION: Hospital facilities and culture, pre-hospital delay and infarction size play a major role in management decisions regarding reperfusion therapy in ST-elevation acute coronary syndrome. This analysis indicates which factors require special attention when implementing and reviewing the reperfusion guidelines.