Rates of clinical remission and inadequate response to advanced therapies among patients with ulcerative colitis in Germany.

PURPOSE: Many patients treated for ulcerative colitis (UC) do not achieve clinical remission. This real-world study assessed clinical remission and inadequate response rates among patients with UC in Germany treated with advanced therapies. METHODS: This retrospective chart review included patients with UC newly initiating advanced (index) therapy (anti-TNFα agents, vedolizumab, tofacitinib) from January 2017-September 2019 (index date). Included patients had data for ≥ 12 months before (baseline period) and after the index date (follow-up period). Remission was defined as a partial Mayo score ≤ 1. Indicators of inadequate response were: index therapy discontinuation; therapy adjustments (index therapy dose escalation; augmentation with non-advanced therapies; corticosteroid [CS] use during maintenance therapy); CS dependency (use for ≥ 12 weeks); and UC-related hospitalisation, surgery or emergency department visit. Time to first remission and inadequate response were analyzed using Kaplan-Meier analyses. RESULTS: Among 149 patients with UC (median age: 40 years), 96 (64.4%) were biologic-naïve and 42 (28.2%) received CS at the index date. Within 12 months, 52 patients (47.2%) were in remission; of these, 13 patients (25.0%) received ≥ 1 therapy adjustment. At 12 months, 55 patients (37.6%) had ≥ 1 indicator of an inadequate response. Median time to remission was longer among biologic-experienced vs biologic-naïve patients (24 vs 7 months; p = 0.012). CONCLUSION: Over half of the patients were not in clinical remission after 12 months and more than one-third experienced inadequate response. One-quarter of patients in remission required therapy adjustments. Patients with UC require therapies that are more effective than those currently available to achieve better treatment outcomes.

Inadequate Response, Treatment Patterns, Health Care Utilization, and Associated Costs in Patients With Ulcerative Colitis: Retrospective Cohort Study Based on German Claims Data.

BACKGROUND: Real-world data regarding response rates in ulcerative colitis treatment are rare, particularly for later lines of therapy. This study aimed to assess continuity of and changes to advanced therapies, as well as costs and specific indicators defining suboptimal therapy. METHODS: German claims data were retrospectively analyzed (January 2014 to June 2019). Patients with ulcerative colitis initiating an advanced therapy (adalimumab, golimumab, infliximab, tofacitinib, vedolizumab) were included. Inadequate response was indicated by therapy discontinuation, switch, escalation, augmentation, corticosteroid dependency, disease-related hospitalization, or surgery. Health care resource utilization (inpatient, outpatient, sick leaves, medication, aids, and remedies) and related costs were assessed from therapy initiation until discontinuation or loss to follow-up. RESULTS: Among 574 patients (median age, 39 years; female sex, 53.5%) who initiated advanced therapies, 458 (79.8%) received an antitumor necrosis factor therapy, 113 (19.7%) vedolizumab, and 3 (0.5%) tofacitinib. After 12 months, 75% had ≥1 indicator for suboptimal therapy. The median time to first indicated inadequate response was 4.8 months. Therapy discontinuation (38%), switching (26%), and prolonged use of steroids (36%) were common within the first year of treatment. In an unadjusted comparison, all-cause total costs per person-year were significantly higher in those who switched vs patients remaining on their therapy (€44,570 vs €36,807; P < .001). CONCLUSIONS: Our study indicates a high prevalence of inadequate response to advanced therapies. Only 25% of patients showed adequate response within 12 months after therapy initiation. Frequent dose and treatment changes were observed. The economic impact of suboptimal therapy in ulcerative colitis is substantial, highlighting the ongoing need for improved treatment strategies.

Management of patients with atrial fibrillation by primary-care physicians in Germany: 1-year results of the ATRIUM registry.

BACKGROUND: Patients with atrial fibrillation (AF) in Germany are often managed jointly by primary-care physicians in cooperation with cardiologists. We aimed to investigate the management and 1-year outcomes of AF patients in this setting. HYPOTHESIS: We set out to describe the current management of AF patients in primary care settings in Germany. METHODS: Observational registry with 1-year follow-up, performed by a representative, randomly selected sample of 781 primary-care physicians in Germany. RESULTS: Of 3781 patients with electrocardiographically documented AF, 3163 patients (age 71.9 ± 9.2 years, 57.9% males) were followed for 1 year; 28.4% had paroxysmal, 27.0% persistent, and 43.3% permanent AF. Comorbid conditions were common (mean CHA2 DS2-VASc score 3. 8 ± 1.7). Rhythm-control therapy was used in 16.4%. Although oral anticoagulation was often used (82.7% at baseline), stroke rate during follow-up was high (2.7% stroke, 3.0% transient ischemic attack). Despite a long duration of AF (mean duration 61 months at enrollment), 18.5% of patients were hospitalized during the 1-year follow-up. CONCLUSIONS: In this unselected group of patients with long-standing AF managed in primary care, hospitalizations and cardiovascular complications including strokes are frequent, illustrating the need to improve management of AF patients.

Improved detection of paroxysmal atrial fibrillation utilizing a software-assisted electrocardiogram approach.

BACKGROUND: Automated complexity-based statistical stroke risk analysis (SRA) of electrocardiogram (ECG) recordings can be used to estimate the risk of paroxysmal atrial fibrillation (pAF). We investigated whether this method could improve the reliability of detection of patients at risk for pAF. METHODS AND RESULTS: Data from 12-lead ECGs, 24-h Holter ECGs, and SRA based on separate 1-hour Holter ECG snips were collected from three groups: 70 patients with a history of pAF but who showed no AF episode in the 12-lead ECG at study entry; 19 patients with chronic AF (at study entry); and 100 young healthy individuals. AF episodes were detected by Holter ECG in 19 of the 70 non-chronic AF patients (27.1% overall, 18.6% in the first hour), and 37 of these 70 patients were classified as at risk for pAF by SRA (representing a sensitivity of 52.9% based on the first hour of analyzed recording). Fifty-four of the 70 patients also showed a sinus rhythm in the first hour. SRA detected pAF risk in 23 of these 54 patients (representing a sensitivity of 42.6%). The Holter data showed at least 1 AF episode and at least 1 hour of sinus rhythm in nine of the patients with pAF. For these patients, SRA classified 77.8% as being at risk in the first hour after the end of the AF episode, and 71.4% and 42.9% as being at risk in the second and third hours, respectively. SRA detected almost all cardiologist-confirmed AF episodes that had been recorded in 1-hour ECG snips (sensitivity, 99.2%; specificity, 99.2%). CONCLUSIONS: This outpatient study confirms previous findings that routine use of SRA could improve AF detection rates and thus may shorten the time between AF onset and initiation of prevention measures for patients at high risk for stroke.

Improved detection of silent atrial fibrillation using 72-hour Holter ECG in patients with ischemic stroke: a prospective multicenter cohort study.

BACKGROUND AND PURPOSE: Adequate diagnosis of atrial fibrillation (AF), including paroxysmal AF, is an important part of stroke workup. Prolonged ECG monitoring may improve the detection of paroxysmal, previously undiagnosed AF (unknown AF). Therefore, we evaluated systematic 72-hour Holter ECG monitoring to detect unknown AF for the workup of patients with stroke. METHODS: Unselected survivors of a stroke or transient ischemic attack (TIA) without known AF were enrolled in a prospective, multicenter cohort study of 72-hour Holter ECG monitoring in 9 German secondary and tertiary stroke centers between May 2010 and January 2011. In addition to standardized workup of stroke pathogenesis according to the German Stroke Unit protocol, all patients underwent 72-hour Holter ECG monitoring directly after admission. All ECGs were centrally analyzed by 2 independent observers. We determined the proportion of unknown AF and compared the detection rates of 72- and 24-hour monitoring. RESULTS: A total of 1135 patients were enrolled (mean age, 67 years [SD, 13.1 years], 45% women, 29% TIA). Unknown AF was detected in 49 out of 1135 patients (4.3%, [95% confidence interval, 3.4-5.2%]) by 72-hour ECG monitoring. Unknown AF was diagnosed in 29 patients (2.6%) within the first 24 hours of ECG monitoring, and in 20 more patients only by 72 hours of ECG monitoring. The number needed to screen by 72-hour ECG was 55 patients (95% confidence interval [35-123]) for each additional AF diagnosis. Patients with unknown AF were significantly older and had more often a history of previous stroke. Patients with unknown AF were equally distributed within categories of pathogenesis according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. CONCLUSIONS: In unselected survivors of stroke or TIA, 72-hour ECG monitoring is feasible and improves the detection rate of silent paroxysmal AF.

Vascular risk prediction in ischemic stroke patients undergoing in-patient rehabilitation - insights from the investigation of patients with ischemic stroke in neurologic rehabilitation (INSIGHT) registry.

BACKGROUND: In-patient rehabilitation following ischemic stroke offers a unique opportunity for risk factor and lifestyle modification. Quantification of risk in this setting may help to tailor therapy, increase physician awareness and patient compliance and thus to reduce recurrent vascular events. AIMS: To validate the predictive value of established secondary stroke risk scores. METHODS: One thousand one hundred sixty-three patients undergoing in-patient rehabilitation following recent ischemic stroke in 15 German neurologic rehabilitation centers were included 0·9 ± 0·5 months after the index event. Outcome information was available for 846 participants (72·7%) after a mean follow-up of 13 ± 2·3 months. RESULTS: Patients' mean age was 66·3 ± 12·3 years and 42·5% were women. The National Institutes of Health Stroke Scale (mean 4·0 ± 3·9), modified Rankin scale (median 2, range 0-5), and Barthel Index (median 90, range 0-100) indicated good functional status. A recurrent fatal or nonfatal stroke during follow-up occurred in 6·7% and combined vascular events (stroke, myocardial infarction, vascular death) in 10·9%. The predictive accuracy for recurrent stroke was slightly higher on the Essen Stroke Risk Score than on the Stroke Prognostis Instrument II (area under the curve 0·62 vs. 0·56), while both scores had a similar predictive accuracy for combined vascular events. CONCLUSIONS: Risk stratification on the Essen Stroke Risk Score and Stroke Prognostis Instrument II provides a moderate accuracy for the prediction of recurrent stroke and vascular events in patients undergoing neurologic in-patient rehabilitation. Although individual risk prediction may remain imprecise, the use of these scores should be encouraged.

Microalbuminuria indicates long-term vascular risk in patients after acute stroke undergoing in-patient rehabilitation.

BACKGROUND: Patients in neurologic in-patient rehabilitation are at risk of cardio- and cerebrovascular events. Microalbuminuria (MAU) is frequent and an important risk predictor but has not been validated in in-patient rehabilitation. We therefore aimed to examine MAU as an indicator of risk and predictor of vascular events in a prospective study. METHODS: The INSIGHT (INvestigation of patients with ischemic Stroke In neuroloGic reHabiliTation) registry is the first to provide large scale data on 1,167 patients with acute stroke (< 3 months) that survived the initial phase of high risk and were undergoing neurologic in-patient rehabilitation. MAU was determined by dipstick-testing and correlated to baseline clinical variables (stroke-origin, functional impairment, co-morbidity, ankle-brachial-index, intima-media-thickeness) as well as vascular events after one year of follow-up. Comparisons were made with the χ2 or Mann-Whitney-U Test. Relative risks (RR) with 95% confidence intervals (CI) were estimated using log-binominal models. To evaluate the association between MAU and new vascular events as well as mortality, we calculated hazard ratios (HR) using Cox proportional hazard regression. RESULTS: A substantial proportion of patients was MAU positive at baseline (33.1%). Upon univariate analysis these patients were about 4 years older (69 vs. 65 years; p < 0.0001), had a slightly higher body mass index (27.8 vs. 27.1 kg/m2; p = 0.03) and increased waist circumference (79.5 vs. 50.4% for women [p < 0.0001] and 46.8 vs. 43.2% for men [p = 0.04]) and twice as often had diabetes mellitus (41.8 vs. 20.1%; p < 0.0001). Patients with MAU had a similar NIH stroke scale score (median 3 vs. 3; p = 0.379) but had lower values on the Barthel Index (median 75 vs. 90; p < 0.001). They had higher rates of atrial fibrillation (RR 1.38; 95% CI 1.09-1.75), coronary artery disease (RR 1.54; 95% CI 1.18-2.00), heart failure (RR 1.70; 95% CI 1.10-2.60) symptomatic peripheral artery disease (RR 2.30; 95% CI 1.40-3.80) and atherosclerotic stroke etiology (53.7 vs. 35.4%; p < 0.0001). MAU was associated with an increased intima-media-thickness, decreased ankle-brachial-index and polyvascular disease (RR 1.56; 95%CI 1.31-1.99). The event rate after a median follow-up of 13 months was 6.7% for fatal or nonfatal stroke, 4.7% for death, and 10.9% for combined vascular events (stroke, MI, vascular death). The presence of MAU was predictive for vascular events during the following year (HR for total mortality 2.2; 95% CI 1.3-3.7; HR for cardiovascular events 2.3; 95% 1.2 - 4.4). CONCLUSIONS: INSIGHT demonstrated a significant association between MAU and polyvascular disease and further supports previous findings that MAU predicts cardio-/cerebrovascular events in patients recovering from ischemic stroke. This biomarker may also be used in patients during neurologic in-patient rehabilitation, opening a window of opportunity for early intervention in this patient group at increased risk for recurrent events.

Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options--a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference.

While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.

Management of atrial fibrillation by primary care physicians in Germany: baseline results of the ATRIUM registry.

BACKGROUND: In contrast to surveys in cardiologist settings, presentation and management of atrial fibrillation (AF) in primary care patients is less well studied. METHODS AND RESULTS: The prospective ATRIUM (Outpatient Registry Upon Morbidity of Atrial Fibrillation) collected data from patients with AF seen by 730 physicians representing a random sample of all primary care physicians in Germany. ATRIUM enrolled 3,667 patients (mean age, 72 ± 9 years; 58% male, mean CHADS(2) score 2.2 ± 1.3), 994 (27.1%) with paroxysmal, 944 (25.7%) with persistent or long-standing persistent and 1,525 (41.6%) with permanent AF (no AF type was specified in 204 patients). Mean duration since initial diagnosis of AF was 61 ± 66 months (median 42, interquartile range 14-88). Reported symptoms included palpitations (43%), shortness of breath (49%), fatigue (49%), dizziness (37%) and angina (20%). Most common concomitant conditions were hypertension (84%), heart failure (43%), coronary artery disease (345%), diabetes (35%) and chronic kidney disease (20%). Prior myocardial infarction was present in 11% of patients, prior stroke in 10% and prior transient ischemic attack in 10%. Antithrombotic medication was used by 93% of the patients (oral anticoagulants, 83%). Rate control therapy was reported in 75% and rhythm control therapy in 33%, often added to rate control. Drugs for rhythm and rate control included ß-blockers (75%), calcium antagonists (15%), digitalis (29%), sodium channel blockers of type IA (quinidine, 1.0%) or IC (flecainide or propafenone, 5%), and potassium channel blockers including amiodarone (11%). In the year prior to enrollment, 46% of the patients had been cardioverted (23% by drugs, 22% electrically), catheter ablation had been performed in 5%, and 10% received a pacemaker or defibrillator. A high proportion (44%) of the patients were hospitalized in the year prior to enrollment. CONCLUSIONS: Patients with AF managed in primary care often receive guideline-conforming therapy including antithrombotic therapy, rate control and rhythm control (numbers given above). Despite this apparent adherence, almost half of the patients were hospitalized in the year prior to enrollment, suggesting that the therapies applied do not stabilize patients sufficiently to keep them out of hospital.

Presentation of atrial fibrillation and its management by cardiologists in the ambulatory and hospital setting: MOVE cross-sectional study.

OBJECTIVE: The aim of the study was to collect comprehensive data on atrial fibrillation (AF) in ambulatory and hospital-based management in Germany. METHODS: Consecutive patients with ECG-confirmed AF in the previous 12 months were documented in a non-interventional study in 638 physician offices (78.0%) or hospitals (12.7%). RESULTS: Of the 3354 patients (mean age 68.9 ± 10.1 years; CHADS(2) score 1.9 ± 1.3), a total of 1136 (33.9%) had paroxysmal, 899 (26.8%) persistent, 1295 (38.6%) permanent and 24 (0.7%) unspecified AF. In the 12 months prior to documentation, pharmacological conversion was attempted in 18.2%, electric cardioversion in 17.5%, the combination of both in 31.2%, and catheter ablation of AF in 5.5%. Only 41.4% of patients met the definition of stable disease (having neither AF related intervention nor change in antiarrhythmic therapy in the previous 12 months). As treatment strategy, physicians stated rate control in 64%, rhythm control in 8%, and both in 19% (not reported: 8%). Patients received antiarrhythmic drugs of class IA in 1.3%, IC in 13.8%, II in 78.1%, III in 17.9%, IV in 9.7% and digitalis in 26.7%. Drugs for thromboembolic prevention (oral anticoagulants and/or antithrombotics) were administered in 81.5%. Hospitalisations for AF or associated diseases in the previous 12 months were reported in 34.2%. Possible limitations include the open, observational design, selection of physicians with particular interest in the field and selection of patients (i.e. underrepresentation of critically ill individuals). CONCLUSIONS: While treatment rates with regards to the prevention of thromboembolic events were among the highest reported to date, the low proportion of stable patients and in particular, the high hospitalisation rate hint at difficulties in the management of patients with AF in clinical practice.

Blood pressure management in a cohort of hypertensive patients in Germany treated by cardiologists.

BACKGROUND: In Germany, an estimated 20-25 million patients suffer from hypertension. Blood pressure control rates are, however, lower than in many other European countries and the USA. The present analysis reports blood pressure treatment and control rates in Germany in patients with hypertension treated by cardiologists. METHODS: The present analysis reports data from a German subgroup analysis of a large, multinational, observational survey i-SEARCH that recruited patients in 2005/2006. It reports blood pressure readings, drug utilization and control rates in cardiology practice. RESULTS: A total of 4,982 patients were documented at 417 sites. Mean systolic/diastolic blood pressure (SBP/DBP) was 152 ± 19.5/88.4 ± 11.5 mmHg. SBP was 1.3 mmHg higher in men than in women (p = 0.021). The majority of patients had an SBP between 141 and 160 mmHg and 31.4% of patients had normal SBP. Overall blood pressure control rate was only 11.6% [95% CI 10.7-12.6] in treated patients. It was different in men [10.2%; 95% CI 9.0-11.6] than in women [8.1%; 95% CI 7.1-9.4; p = 0.008] and higher in patients without diabetes [12.7%; 95% CI 11.6-14.0] than in those with diabetes [4.3%; 95% CI 3.4-5.4; p < 0.0001]. One-third of patients received either monotherapy or dual therapy, or three and more drugs, respectively; 42.2% of patients received guideline-recommended dual combination therapy. A combination of beta-blockers + ACE inhibitors was most frequently prescribed (30.8%). CONCLUSIONS: Our data indicate a low level of blood pressure control, especially in patients at an increased risk for cardiovascular events, such as those with diabetes or cardiovascular comorbidities. Major efforts are required to improve hypertension management as recommend by current treatment guidelines.

Contrast-Enhanced Transcranial and Extracranial Duplex Sonography: Preliminary Results of a Multicenter Phase II/III Study with SonoVuetrade mark.

Transcranial sonography is an ultrasonographic application with real problems of insufficient signal to noise ratio, which make it a primary candidate for applying ultrasonographic contrast enhancing agents. Within an international randomized multicenter phase II/III study, we investigated ten patients with insufficient Doppler signal retrieval using transcranial and extracranial color-coded duplex sonography to define safety, toxicity, optimal dosing, and the potential of the new ultrasound contrast agent SonoVue(trade mark). Patients were studied with standard color duplex systems. SonoVue(trade mark) was administered by IV bolus injection at four different doses. Efficacy parameters included the assessment of global quality of Doppler investigations, color Doppler (CD), and spectral Doppler (SD) evaluated by semiquantitative analysis using a four-point scale from 0 to 3 (very poor to excellent) and the duration of clinically useful signal enhancement. In addition, CD enhancement, evaluated at best signal enhancement, was assessed using a five-point scale, from no enhancement, slight, moderate, optimal to excessive (0-4). All examinations were compared to "gold" standard imaging (magnetic resonance imaging, digital subtraction angiography) to evaluate diagnostic confidence at optimum dosage. No serious adverse events were observed. Mean signal increase over baseline in CD or SD was 2 out of 4 points. Mean time to appearance of contrast enhancement was 22.8 seconds (9-52 sec) at the optimal dosage. The mean duration of enhancement was 281 seconds(20-593 sec) at the optimal dosage, which was of 2.4 ml of SonoVuetrade mark in nine patients. CD and SD signal enhancement (n = 20, CD + SD) was considered optimal in 12 of 20, excessive in 1 of 20, and moderate or insufficient in 5 of 20 and 2 of 20 cases, respectively. There was a tendency for superior improvement in CD signal enhancement. Diagnostic confidence was improved in 8 of 10 cases without false diagnostic conclusions. SonoVuetrade mark has been demonstrated to be a powerful and safe echo signal enhancing agent, which significantly improves transcranial and extracranial ultrasound investigations and increases the confidence in diagnosis.