Eva-Maria Fronk

The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry.

BackgroundVenous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement.Methods/designThe PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls.ResultsOverall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year.ConclusionThe PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice.Trial registrationRegistered in DRKS register, ID number: DRKS00004795

Effectiveness and tolerability of a fixed-dose combination of olmesartan and amlodipine in clinical practice

Objectives: To assess the efficacy and tolerability of a fixed-dose combination of olmesartan and amlodipine in an unselected population of patients in primary care and to compare the results with recent randomized controlled trial evidence. Methods: A multicenter, noninterventional, noncontrolled observational study with 8241 hypertensive patients seen by 2187 physicians in daily practice. Blood pressure (BP) reduction, comorbid disease, pharmacotherapy, and tolerability were documented over a 12–18-week observational period. Results: Patients had a mean age of 62.8 ± 11.8 years (48.1% female), and 74.8% had at least one comorbid risk factor or condition. In total, 51.3% received olmesartan-amlodipine 20/5 mg, 30.6% received 40/5 mg, and 17.9% received 40/10 mg at baseline, mostly because of lack of efficacy on prior antihypertensive therapy (73.8%). BP at baseline was 161.8 ± 16.6/93.6 ± 10.2 mmHg (39.8% had Grade 2 hypertension), and the observed BP reduction was −29.0 ± 17.1/−13.5 ± 10.9 mmHg (P < 0.0001), with a significant correlation between BP at baseline and BP reduction (Spearman’s Rho −0.811 for systolic BP and −0.759 for diastolic BP). BP reduction appeared to be dependent on dose and prior antihypertensive therapy, but not on age, gender, body mass index, duration of hypertension, or the presence of diabetes. At the final visit, 69.4% (4.3% at baseline) were controlled (<140/90 mmHg). Adverse drug reactions were observed in 2.76% of the study population; 94.25% of these adverse drug reactions were judged as nonserious events, and 31.5% of all adverse drug reactions reported were peripheral edema. Conclusion: The fixed-dose olmesartan-amlodipine combination was effective and well tolerated in an unselected population of patients in primary care practice. These results confirm prior randomized controlled trial evidence.

The management of acute venous thromboembolism in clinical practice

Summary Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0% were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5%). The diagnosis was deep-vein thrombosis (DVT) in 59.5% and pulmonary embolism (PE) in 40.5%. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5%), hypertension (42.3%) and dyslipidaemia (21.1%). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2%), almost half received a vitamin K antagonist (48.7%) and nearly a quarter received a DOAC (24.5%). Almost a quarter of all presentations were for recurrent VTE, with >80% of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes.Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0% were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5%). The diagnosis was deep-vein thrombosis (DVT) in 59.5% and pulmonary embolism (PE) in 40.5%. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5%), hypertension (42.3%) and dyslipidaemia (21.1%). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2%), almost half received a vitamin K antagonist (48.7%) and nearly a quarter received a DOAC (24.5%). Almost a quarter of all presentations were for recurrent VTE, with >80% of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes.

Safety and effectiveness of a fixed-dose combination of olmesartan, amlodipine, and hydrochlorothiazide in clinical practice

Background Clinical trials indicate that the use of fixed-dose combinations (FDCs) is associated with a higher level of treatment adherence and prolonged blood pressure (BP) control. The aim of this study was to document the safety and effectiveness of the FDC olmesartan/amlodipine/hydrochlorothiazide in patients with essential hypertension in clinical practice. Methods This multicenter, prospective, 24-week, noninterventional study enrolled 5,831 patients from primary care offices in Germany and Austria. Inclusion criteria were a diagnosis of essential hypertension and newly initiated treatment with the FDC. Results The mean age of patients was 63.5 years, almost 50% of patients had a time since diagnosis of essential hypertension of over 5 years, and approximately 70% of patients had at least one cardiovascular risk factor, including 29.4% of patients with diabetes mellitus. Following approximately 24 weeks of treatment, the mean reduction in systolic/diastolic BP was 29.0/14.0 mmHg, a BP response was observed by 94.2% of patients, and a target BP of <140/90 mmHg was attained in 67.5% of patients. At least one adverse drug reaction (ADR) was experienced by 1.2% of patients, with the most common being peripheral edema. Subanalyses demonstrated that the following factors did not have a significant influence on the ADR rate: age (<65 years versus ≥65 years), diabetes mellitus (no/yes), cardiovascular risk (low/high), and concomitant medication (no/yes). Conclusion This study demonstrates that in clinical practice, treatment with the three-drug combination as an FDC tablet resulted in a very high proportion of patients with a BP response and control, accompanied by a very low rate of ADRs.

Improving quality of life in hypertension management using a fixed-dose combination of olmesartan and amlodipine in primary care.

Objectives. To assess quality of life (QoL) in unselected patients in primary care treated with a fixed-dose combination of olmesartan and amlodipine. Research design and methods. Multicenter, noninterventional, noncontrolled observational study in 8241 patients seen by 2187 physicians over 12 – 18 weeks. Main outcome measures. Changes in QoL were assessed by using the Short Form 12 (SF-12) questionnaire completed by 5434 patients (65.9%) at baseline and 4924 patients (59.8%) at the follow-up visit. Results. Patients had a mean age of 62.8 ± 11.8 years (48.1% female), mean blood pressure [BP] at baseline was 161.8 ± 16.6/93.6 ± 10.2 mmHg and 74.8% had at least one co-morbid risk factor or condition. All 12 items of the SF-12 improved over the observational period (p < 0.0001) as did the physical (46.8 vs 40.4; p < 0.0001) and mental summary scores (52.4 vs 47.5; p < 0.0001). Correlations of changes in systolic and diastolic BP, pulse pressure and heart rate with scores were significant, although weak (maximum -0.2055 for physical health and changes in systolic blood pressure). Conclusions. The fixed-dose combination of olmesartan and amlodipine significantly improves QoL in an unselected population of patients in primary-care practice. This might translate into improved patient compliance and improved long-term antihypertensive efficacy.

Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40 mg and hydrochlorothiazide 12.5/25 mg in daily practice

Background The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ) as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control. Methods In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs. Results The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19), and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P < 0.0001), but had reduced effectiveness in patients ≥75 years with diabetes or impaired renal function. In 69% of patients, blood pressure was normalized (<140/90 mmHg). No noteworthy differences in baseline characteristics or baseline blood pressure were found between patients with an activity level (sum of weekly energy costs) above or below the median of 9,460.6. A higher versus lower physical activity score had no impact on blood pressure reduction. Conclusion Our data confirm randomized trial data concerning safe and efficient blood pressure reduction using a fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg in a large, unselected patient population, independent of physical activity level.

The role of heparin lead-in in the real-world management of acute venous thromboembolism: The PREFER in VTE registry

INTRODUCTION The appropriate strategy for initiating oral anticoagulant (OAC) therapy after an acute venous thromboembolism (VTE) depends on the intermediate-term anticoagulant to be used. While heparin bridging to vitamin K antagonists (VKA) is required, the direct oral anticoagulants (DOAC) rivaroxaban (30mg/day) and apixaban (10mg/day) can be initiated directly without parenteral anticoagulation. The objective was to evaluate OAC initiation patterns in clinical practice. MATERIALS AND METHODS PREFER in VTE was an international, non-interventional registry conducted between January 2013 and August 2015. Consecutive acute VTE patients were grouped based on their OAC treatment at 1month after the index event (VKA or DOAC). RESULTS At 1month, 825 patients were receiving a VKA and 687 a DOAC (rivaroxaban in 685/687 cases). DOAC patients were significantly younger, less comorbid, at a lower bleeding risk, and less frequently diagnosed with pulmonary embolism (34.4% vs. 44.7%). During the first month after VTE, the most common treatment pattern was heparin-OAC overlap for VKA patents (69.6%), and OAC only for DOAC patients (49.1%). However, 28.8% of DOAC patients received a heparin-OAC overlap (median heparin duration: 3days; IQR: 2-6) and 14.8% were switched from heparin to DOAC. For those on rivaroxaban at 1month, only 29.7% had received the initial 30mg/day recommended dose. Clinical event rates were comparable between the DOAC only, heparin-DOAC switch, and heparin-DOAC overlap subgroups at 1 and 6months. CONCLUSIONS Guidelines for DOAC/rivaroxaban initiation after VTE are often not adhered to in clinical practice. This could result in adverse outcomes or suboptimal anticoagulation. Intervention programs to raise awareness amongst physicians may be merited.

Quality of life and emotional impact of a fixed‐dose combination of antihypertensive drugs in patients with uncontrolled hypertension

Often considered to be a symptomless condition, hypertension can be associated with a significant emotional burden. To analyze changes of health‐related quality of life as well as the emotional burden questions regarding the impact of hypertension were incorporated into the noninterventional SeviTarget study. Comparisons were made between baseline and follow‐up findings, and between patients with treatment target achievement and those without. A total of 5831 patients were recruited. At baseline, only 33.3% of patients described their current state of health as good or excellent, while at follow‐up this value had risen to 75.8%. Responses regarding symptoms and limitations in activities and mental factors such as anxiety associated with treatment all improved during antihypertensive treatment. Changes to more optimistic responses were more likely for patients who achieved a target BP of <140/90 mm Hg. The study demonstrates that improvements in quality of life and the perceived emotional burden related to hypertension can be achieved with effective management of hypertension.