Publikationen

Groth A, Halder F, Fuchs A, Maywald U, Wilke T. Unterversorgung von Vorhofflimmer-Patienten mit oralen Antikoagulanzien in Deutschland. Der Kardiologe. 2015 Okt, 9(5):379-392

Abstract

Hintergrund und Ziel

Eine orale Antikoagulation (OAK) mit Vitamin-K-Antagonisten (VKA) oder neuen oralen Antikoagulanzien (NOAK) wird nach deutschen und internationalen Leitlinien für Patienten mit Vorhofflimmern (VHF) und hohem Schlaganfallrisiko (CHA₂DS₂-VAS_C > 1) empfohlen. Ziel des Reviews ist es, die bisherige Evidenz zum Ausmaß an OAK-Unterversorgung von VHF-Patienten in Deutschland sowie potenzielle Gründe für eine bestehende Unterversorgung systematisch darzustellen.

Methode

In Bezug auf das Ausmaß an OAK-Unterversorgung erfolgte eine Auswertung der deutsch- und englischsprachigen Literatur, die das deutsche Versorgungsumfeld thematisierte. Bei der Ermittlung von Ursachen für OAK-Unterversorgung wurde mangels deutscher Daten die gesamte relevante internationale Literatur in die Übersicht einbezogen.

Ergebnisse

Es wurden 4 Beiträge, die sich dem Thema der OAK-Unterversorgung von VHF-Patienten in Deutschland widmeten sowie 87 Publikationen, die Ursachenfaktoren für OAK-Unterversorgung thematisierten, identifiziert. Etwa 50 % der in Deutschland behandelten VHF-Patienten sind von OAK-Unterversorgung betroffen. OAK-Unterversorgung ist dabei ein Versorgungsdefizit, das auf multivariate Ursachenfaktoren zurückzuführen bzw. mit unterschiedlichen Faktoren assoziiert ist. Dabei können 4 wesentliche Gruppen von Ursachenfaktoren mit einigen dominierenden spezifischen Ursachen unterschieden werden: patientenbezogene medizinische Faktoren (frühere Blutungen und Blutungsrisiko, Sturzgefahr, Krebserkrankungen, paroxysmales VHF statt permanentes/persistierendes VHF), allgemeine Charakteristika von Patienten (hohes Alter, Non-Adhärenz), arztassoziierte Faktoren (Arztwissen und arztseitige Nutzeneinschätzung der OAK) sowie sonstige, i. d. R. im Versorgungsumfeld der Patienten befindliche Faktoren (Logistik, u. a. im Kontext der „Internal-normalized-ratio“(INR)-Kontrollen).

Schlussfolgerung

Eine korrekte OAK-Versorgung von VHF-Patienten stellt eine große Herausforderungdar. Versorgungsprogramme, die die OAK-Versorgung von VHF-Patienten zu optimieren versuchen, sollten die Multivariabilität der Ursachen der Unterversorgung beachten.

Wilke T, Mueller S, Groth A, Fuchs A, Seitz L, Kienhöfer J, Maywald U, Lundershausen R, Wehling M. Treatment-dependent and treatment-independent risk factors associated with the risk of diabetes-related events: a retrospective analysis based on 229,042 patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2015 Feb 3;14(1):14.

Abstract

Background

The aim of this study was to analyse which factors predict the real-world ma-cro-/microvascular event, hospitalisation and death risk in patients with type 2 diabetes mellitus. Furthermore, we aimed to investigate whether there exists both an under- and over-treatment risk of these patients.MethodsWe used a German claims/clinical data set covering the years 2010¿12. Diabetes-related events were defined as ( macro-, microvascular events leading to inpatient hospitalisation,  other hospitalisations with type 2 diabetes mellitus as main diagnosis, all-cause death and  a composite outcome including all event categories 1¿4. Factors associated with event risk were analysed by a Kaplan-Meier curve analysis and by multivariable Cox regression models.Results229,042 patients with type 2 diabetes mellitus (mean age 70.2 years; mean CCI 6.03) were included. Among factors that increased the event risk were patients¿ age, male gender, the adapted Charlson Comorbidity Index, the adapted Diabetes Complication Severity Index, previous events, and number of prescribed chronic medications. For systolic blood pressure/HbA1C, a double-J/U-curve pattern was detected: HbA1C of 6¿6.5% (42-48 mmol/mol) and systolic blood pressure of 130-140 mmHg (17.3-18.7kPa) were associated with the lowest event risk, values below/above that range were associated with higher risk. However, this pattern was mainly driven by the death risk and was much less clearly observed for the macrovascular/microvascular/hospitalization risk and for young/less comorbid patients.ConclusionsBoth blood pressure and HbA1C seem to be very important treatment targets, especially in comorbid old patients. It is of particular clinical importance that both over- and under-treatment pose a threat to patients with type 2 diabetes mellitus.

Müller S, Wilke T. Validation of the Adherence Barriers Questionnaire (ABQ) – An Instrument for Identifying Potential Risk Factors Associated With Medication-Related Non-Adherence. Value in Health. 2014;17(7):A512.

Abstract

OBJECTIVES

Medication-related non-adherence is a major challenge in the real-life treatment of patients. To meet this challenge successfully, adherence interventions with a tailored approach towards patient-specific adherence barriers are needed. Therefore, a reliable and practicable questionnaire for identification of those adherence barriers in specific patients is needed. The aim of this investigation is to develop and validate such a questionnaire.

METHODS

The “Adherence Barriers Questionnaire (ABQ)” was developed and tested in 432 patients with atrial fibrillation in a multicenter observational cohort study. Evaluation of the questionnaire included an assessment of internal consistency as well as factor analysis. Criterion-related external validity was appraised by comparing the ABQ score with the score of a self-report adherence measure and with a clinical parameter (time in therapeutic range (TTR) regarding INR values in the VKA-based stroke prophylaxis treatment of patients).

RESULTS

The final 14-item ABQ scale demonstrated high internal consistency (Cronbach’s alpha=0.820). Factor analysis identified a three-factor solution, representing intentional adherence barriers with 5 items (31.9% of the variance), medication- or health care system-related adherence barriers with 5 items (13.3% of the variance) and unintentional adherence barriers with 4 items (7.7% of the variance).

The ABQ correlated significantly with self-reported non-adherence (Spearman’s rho=0.438, P<0.001) as well as TTR (Spearman’s rho=-0.161, P<0.01). Patients with above-average ABQ scores (increased number of existing adherence barriers) were significantly (p<0.005, Pearson Chi-Square) more likely to have a poor anticoagulation quality (TTR<60%) than patients with a lower ABQ score (44.6% versus 27.3%).

CONCLUSION

The ABQ is a practicable, reliable and valid instrument for identifying specific barriers to medication-related adherence. Future research is required to examine the ability of the ABQ to identify patient perception/behavior changes over time which may be important for the measurement of success of adherence interventions.

Wilke T, Groth A, Berg B, Sikirica M, Martin AA, Fuchs A, Maywald U. Non-Adherence And Non-Persistence Related To Glp-1 Therapy In Patients With Diabetes Mellitus Type 2 (T2dm): Analysis of A Large German Claims-Based Dataset And Comparison To Oral Anti-Diabetics. Value in Health. 2014;17(7):A359.

Abstract

OBJECTIVES

This study describes the extent of non-adherence (NA) and non-persistence (NP) with Glucagon-like peptide 1 agonists (GLP-1) and oral anti-diabetic (OAD) therapy in T2DM patients in clinical practice in Germany.

METHODS

Claims data from a German sickness fund (AOK Plus) from 2010-2012 were used to identify patients with ≥ 1 diagnosis for T2DM. NA/NP were measured for patients initiating new T2DM medication (no prescription of respective medication in prior 6 months ) over a minimum of 12 months. A 100% adherence to therapy was assumed equivalent to the drug-specific DDD (defined daily dosage). NP was defined as a medication gap ≥ 90 days. Adherence was calculated via medication possession ratios (MPR), NA was defined as MPR<80%. Descriptive analyses with percentage of patients affected by NP and/or NA were conducted.

RESULTS

The NP analysis, included 2,490/42,891 T2DM patients initiating GLP-1s/OADs. Among GLP-1 patients, 408/1,727/135 received twice-daily (BID; exenatide)/once-daily (OD; liraglutide)/once-weekly (OW; exenatide) therapies. Average age for GLP-1/OAD users was 56 (SD 10.8)/67 (SD 12.6) years. After 12 months, the percentage of patients with NP was 36.83% (all GLP-1s), 42.65% (BID), 37.64% (OD), 27.41% (OW), and 55.87% (OAD). The NA analysis included 2,154/34,128 T2DM patients initiating GLP-1/OAD therapy with ≥1 follow-up prescription. Average age was 56 (SD 10.6)/66 (SD 12.2) years. Average MPR was 88.2% (all GLP-1s), 87.8% (BID), 88.2% (OD), 95.0% (OW), and 63.2% (OAD). Percentage of patients affected by NA was 21.96% (all GLP-1s), 23.98% (BID), 22.00% (OD), 5.74% (OW), and 65.82% (OAD).

CONCLUSIONS

In this German dataset, overall patients with T2DM had low rates of adherence and persistence despite the chronic nature of the disease and clinical sequelae. Higher adherence and persistence rates were observed with GLP-1s than with OAD medications and also with less frequently dosed GLP-1s.

Böttger B, Thate-Waschke IM, Bauersachs R, Kohlmann T, Wilke T. Preferences Regarding The Attributes Of Oral Anticoagulants In Patients With Atrial Fibrillation Results Of A Discrete Choice Experiment. Value in Health. 2014;17(7):A495.

Abstract

OBJECTIVES

Since the introduction of new oral anticoagulants (NOACs), an additional option for stroke prevention of patients with atrial fibrillation (AF) compared to vitamin-K-antagonists (VKAs) is available. The objective of this study was to asses patients’ preferences regarding the attributes of these different treatment options.

METHODS

We conducted a multicenter study among randomly selected physicians. Preferences were assessed by computer-assisted telephone interviews. We used a Discrete-Choice-Experiment (DCE) with four treatment dependent attributes (need of bridging: yes/no, interactions with food/nutrition: yes/no, need of INR controls/dose adjustment: yes/no; frequency of intake: once/twice daily) and one comparator attribute (distance to practitioner: <1km/>15km). Preferences measured in the interviews were analyzed descriptively and based on a logistic regression model.

RESULTS

A total of 140 AF patients (age: 74.0±8.5 years; 57.0% male; mean CHA2DS2-VASc: 6.1±1.1; current medication: 27.1% Rivaroxaban, 71.4% VKA, 1.4% other) could be interviewed. Regardless of type of medication, patients significantly preferred the attributes’ level (in order of patients’ importance) “once daily intake” (Level: once = 1 vs. twice = 0; Coefficient = 0.954; p<0.001), “no interactions with food/nutrition” (yes = 1 vs. no = 0; -0.842; p<0.001), “no bridging necessary” (yes = 1 vs. no = 0; -0.656; p<0.001) and “distance to practitioner of ≤ 1 km (> 15 km =1 vs. ≤ 1 km = 0; 0.644; p<0.001). However, for the attribute "need of INR controls/dose adjustment" (Level: yes = 1 vs. no = 0; Coefficient = 0.020; p=0.808) no significant preference in favour of one of the options are shown.

CONCLUSION

In our analyses, “once daily frequency of intake” was the most important attribute for patients’ choice followed by “no interactions with food/nutrition” and “no bridging necessary”. Thus, patients with AF seem to prefer treatment options which are easier to administer. When deciding about medical therapy, patients’ preferences should be considered.

Petersen J, Wilke T, Mauss S, Heyne R, Herold C, Wiese M, Boeker K, Pichl T, Hueppe D. Real-life persistence and adherence in ETV treated chronic hepatitis b patients: results of a German prospective multicenter observational study.  J Hepatol Suppl. 2014;60(1):S423.

Abstract

OBJECTIVES

Entecavir (ETV) is a very effective and safe treatment option in chronic hepatitis B (CHB) patients. However, some patients show only a partial virologic response. The most reasonable explanation is non-persistence/non-adherence. Persistence and adherence measurement is underrepresented in clinical trials. Therefore, the extent of non-persistence (NP), non-adherence (NA) and clinical outcomes of any NA/NP were measured in ETV-treated patients in a real-life study.

METHODS

In a prospective observational multicenter study, persistence and adherence were measured based on documented prescriptions within a 12 month period. A patient was defined as NP if he missed all treatment doses in >30 subsequent days. Adherence was measured based on medication possession ratio (MPR) between first and last documented prescription (NA if MPR<80%). Proportion of patients reaching undetectable HBV-DNA levels (<69IU/mL) was determined.

RESULTS

112 CHB patients were analysed, baseline characteristics and results are presented in table 1. 26.8% of patients (n=30) missed treatment doses in >30 subsequent days (NP group), 30% of patients in the NP group (n=9) and none of the persistent patients were classified as non-adherent. Mean MPR for all patients was 95.3%. 84.4% of persistent/adherent patients and 63.0% of patients in the NP group reached undetectable HBV-DNA levels (p=0.022). So far no significantly correlating factors for NP/NA could be detected.

CONCLUSION

Böttger B, Wehling M, Bauersachs RM, Amann S, Schuchert A, Reinhold C, Kümpers P, Wilke T. Prevalence of renal insufficiency in hospitalised patients with venous thromboembolic events: A retrospective analysis based on 6,725 VTE patients. Thromb Res. 2014;134(5):1014–1019.

Abstract

Wilke T, Groth A, Pfannkuche M, Harks O, Fuchs A, Maywald U, Krabbe B. Real life anticoagulation treatment of patients with atrial fibrillation in Germany: extent and causes of anticoagulant under-use. J Thromb Thrombolysis. 2014;Epub ahead of print

Abstract

Wilke T, Groth A, Fuchs A, Seitz L, Kienhöfer J, Lundershausen R, Maywald U. Real life treatment of diabetes mellitus type 2 patients: An analysis based on a large sample of 394,828 German patients. Diabetes Res Clin Pract. 2014;Epub ahead of print.

Abstract

OBJECTIVES

The aim of this claims-based data analysis was to describe the care of German T2DM patients and to determine which subgroups could be differentiated in terms of the achieved T2DM-related treatment results, the underlying comorbidities, and the achieved comorbidity-related treatment results.

METHODS

We included all T2DM patients insured by a large sickness fund in 2010/2011. We defined 12 subgroups according to observed HbA1C, blood pressure and Charlson Comorbidity Index (CCI). For each subgroup, available sociodemographic and clinical information were reported. Different treatment variables were described. T2DM-related events leading to acute hospitalisations were reported.

RESULTS

We included 394,828 T2DM patients in our analysis; for 228,703 patients’ detailed data as basis for subgroup classification were available. For 4.5% of these patients, a HbA1C >9% was observed.

21,833 of the T2DM patients were affected by a T2DM-related event; the risk was 5.53% per patient year; 1.74% of the patients suffered from more than one event. Most frequent event types were hospitalisation with T2DM as primary diagnosis (2.39%), vascular interventions/stent implantations (1.92%), and ischaemic stroke (1.19%). There were significant differences between the observed subgroups in terms of T2DM-related event risk.

CONCLUSION

Overall, our data indicate that the typically treated T2DM patient has a number of comorbidities and thus treatment focused solely on T2DM is neither possible nor clinically meaningful. Particularly those patients who reached HbA1C goals, but had also achieved relevant additional treatment goals reached low yearly T2DM event rates whereas subgroups failing to achieve one or several treatment goals are facing much higher event risks

Müller S, Pfannkuche M, Breithardt G, Bauersachs R, Maywald U, Kohlmann T, Wilke T. The quality of oral anticoagulation in general practice in patients with atrial fibrillation. Eur J Intern Med. 2014;25(3):247-254.

Abstract

BACKGROUND

The aims of this study were to evaluate the quality of oral anticoagulation (OAC) in AF patients in the practices of general practitioners (GPs) in Germany and to investigate possible causal factors which influence OAC quality.

METHODS

We conducted a multi-center, non-interventional, prospective observational cohort study among general practitioners (GPs) in Germany. To assess the quality of OAC on the basis of the prospectively documented international normalized ratio (INR) values, the time in therapeutic range (TTR) was calculated using the Rosendaal linear trend method. The causes of poor OAC quality were identified by a multivariate analysis model (logistical regression; poor OAC quality: TTR < 60%).

RESULTS AND CONCLUSIONS

For 525 OAC patients (66.8%; patients with at least 2 prospectively documented INR values) the average TTR (target range of 2.0–3.0) was 67.6%. About 34.7% of the patients had a TTR < 60%.

None of the variables representing characteristics of the medical practices were capable of explaining the occurrence of poor OAC quality. However, with regard to care provision-based variables, the existence of a brief discontinuation of medication was important. As the existence of adherence barriers increased, the probability of poor anticoagulation quality increased.