Nils Kuklik

Background: Oral anticoagulation is highly effective in preventing ischemic events in patients with atrial fibrillation. Still, a considerable number of patients have an acute ischemic stroke or transient ischemic attack despite anticoagulation. In this study, we investigated the association of prior antithrombotic regimens with stroke severity, volume, and hemorrhagic transformation. Methods and Results: This is a post hoc analysis of the prospective, multicenter, observational PRODAST (Prospective Record of the Use of Dabigatran in Patients With Acute Stroke or TIA) study, which was conducted in 86 stroke units in Germany between July 2015 and November 2020. In 9030 patients with atrial fibrillation who had an acute ischemic stroke or transient ischemic attack within 7 days before enrollment, we analyzed the association of anticoagulants in comparison to lack of prevalent antithrombotic treatment with clinical stroke severity, infarct size, and risk for hemorrhagic transformation. A total of 4479 patients had prior anticoagulation at the time of index event. After adjustment for confounders (arterial hypertension, diabetes, heart failure, age, and sex), patients with prior anticoagulation had less severe strokes (−2.5 National Institutes of Health Stroke Scale points [95% CI, −2.8 to −2.2]), smaller infarct sizes (−23 mL [95% CI, −44 mL to −2 mL], n=4041), and reduced odds for hemorrhagic transformation (5% versus 10%; odds ratio, 0.48 [95% CI, 0.40–0.57]) compared with patients without antithrombotic treatment. These findings were confirmed using sensitivity analyses accounting for thrombolysis and mechanical thrombectomy, as well as timing of brain imaging. Antiplatelet therapy had hardly any association with the end points compared with no antithrombotic pretreatment. Conclusions: Prior anticoagulation was not only associated with less severe stroke and smaller infarct size but also with a reduced risk of hemorrhagic transformation compared with no antithrombotic pretreatment. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02507856.

Background: Intracranial hemorrhage (ICH) is a rare but serious side effect associated with the use of oral anticoagulants, such as dabigatran. The specific reversal agent for dabigatran, idarucizumab, is available for the management of individuals with ICH. The aim of this study was to provide real-world evidence on patients with ICH and effective treatment with dabigatran and reversal with idarucizumab in clinical routine compared to those under effective treatment with vitamin-K-antagonist (VKA).Methods: Registration of Idarucizumab for Patients with IntraCranial Hemorrhage (RIC-ICH) is a non-interventional study conducted in 22 German stroke units that prospectively enrolled dabigatran patients treated with idarucizumab. Retrospective data from VKA patients served as reference population. Main objective was in-hospital mortality. Further objectives included change in bleeding volume, stroke severity, and functional status.Result: In-hospital mortality was 26.7% in 15 dabigatran and 27.3% in 88 VKA patients (hazard ratio 1.00, 95% CI 0.29–2.60). In patients with bleeding volume > 60 ml, mortality was lower in the dabigatran group (N = 6, 33%) compared to the VKA group (N = 15, 67%; HR 0.24, 95% CI 0.04–0.96). No differences were observed in secondary endpoints between dabigatran and VKA patients.Conclusion: These results, based on data from routine clinical practice, suggest that in-hospital mortality after idarucizumab treatment is comparable to that in patients pretreated with VKA. Due to the low precision of estimates, the results must be interpreted with caution.

Adverse drug events (ADEs) that occur during hospitalization are an ongoing medical concern. Systematic strategies for ADE identification are lacking. The aim of this study was to evaluate the potential to identify adverse drug events caused by medication errors (preventable ADEs, pADEs), and previously unknown adverse drug reactions (ADRs or non-preventable ADEs, npADEs) in inpatients by combining diagnosis codes in routine data with a chart review. Diagnoses of inpatients are routinely coded using the International Classification of Diseases, 10th Revision (ICD-10). A total of 2326 cases were sampled from routine data of four hospitals using a set of ICD-10 German Modification ADE codes. Following a chart review, cases were evaluated in a standardized process with regard to drug relation and preventability of events. By chart review, 1302 cases were classified as hospital-acquired and included in the evaluation. This yielded 1285 cases indicating an ADE. 96.8% of ADEs (1244 ADEs) were classified as known npADEs, only three cases as suspected previously unknown npADEs, one case as event after drug abuse. A total of 37 ADEs were classified as preventable (2.9% of all ADEs) by identifying a medication error as probable cause. The prevalence of pADEs varied considerably between included ADE codes, with hemorrhagic diathesis due to coumarins and localized skin eruptions showing the highest rates (8.7 and 9.1%, respectively). Most frequent medication errors were non-compliance to a known allergy, and improper dose. When focusing on specific ADE codes, routine data can be used as markers for npADEs and medication errors, thus providing a meaningful complement to existing drug surveillance systems. However, the prevalence of medication errors is lower than in former studies on the frequency of pADEs.

Adverse drug events (ADEs) during hospital stays are a significant problem of healthcare systems. Established monitoring systems lack completeness or are cost intensive. Routinely assigned International Statistical Classification of Diseases and Related Health Problems (ICD) codes could complement existing systems for ADE identification. To analyze the potential of using routine data for ADE detection, the validity of a set of ICD codes was determined focusing on hospital-acquired events. The study utilized routine data from four German hospitals covering the years 2014 and 2015. A set of ICD, 10^th Revision, German Modification (ICD-10-GM) diagnoses coded most frequently in the routine data and identified as codes indicating ADEs was analyzed. Data from psychiatric and psychotherapeutic departments were excluded. Retrospective chart review was performed to calculate positive predictive values (PPV) and sensitivity. Of 807 reviewed ADE codes, 91.2% (95%-confidence interval: 89.0, 93.1) were identified as disease in the medical records and 65.1% (61.7, 68.3) were confirmed as ADE. For code groups being predominantly hospital-acquired, 78.5% (73.7, 82.9) were confirmed as ADE, ranging from 68.5% to 94.4% dependent on the ICD code. However, sensitivity of inpatient ADEs was relatively low. 49.7% (45.2, 54.2) of 495 identified hospital-acquired ADEs were coded as disease in the routine data, from which a subgroup of 12.1% (9.4, 15.3) was coded as drug-associated disease. ICD codes from routine data can provide an important contribution to the development and improvement of ADE monitoring systems. Documentation quality is crucial to further increase the PPV, and actions against under-reporting of ADEs in routine data need to be taken.