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Interactive Cardiovascular and Thoracic... Jun 2022Oral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or...
OBJECTIVES
Oral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or reversed in time. The goal of this study was to analyse the impact of different oral anticoagulants on the outcome of patients who underwent emergency surgery for acute type A aortic dissection (ATAAD).
METHODS
This was a single-centre retrospective study of patients treated with oral anticoagulation at the time of surgery for ATAAD. Outcomes of patients on new oral anticoagulant (NOAC) therapy were compared to respective outcomes of patients on Coumadin. Additionally, a survival analysis was performed comparing these 2 groups with patients who were operated on with no prior anticoagulation.
RESULTS
Between January 2013 and April 2020, a total of 437 patients (63.8 ± 11.8 years, 68.4% male) received emergency surgery for ATAAD; 35 (8%) were taking oral anticoagulation at the time of hospital admission: 20 received phenprocoumon; 14, rivaroxaban; and 1, dabigatran. Compared to Coumadin, NOAC was associated with a greater need for blood-product transfusions and haemodynamic compromise. Operative mortality was 53% in the NOAC group and 30% in the Coumadin group. A 5-year survival analysis showed no significant difference between the NOAC and the Coumadin group (P = 0.059). Compared to 402 patients treated during the study period without anticoagulation, patients taking NOAC had significantly worse survival (P = 0.001), whereas that effect was not observed in patients undergoing surgery who were taking Coumadin (P = 0.99).
CONCLUSIONS
Emergency surgery for ATAAD in patients taking NOAC is associated with high morbidity and mortality. NOAC are a major risk factor for uncontrollable bleeding and haemodynamic compromise. New treatment strategies must be defined to improve surgical outcomes in these high-risk patients.
Topics: Administration, Oral; Aortic Dissection; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Retrospective Studies; Warfarin
PubMed: 35258082
DOI: 10.1093/icvts/ivac037 -
Thrombosis and Haemostasis Mar 2022In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that...
BACKGROUND
In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications.
AIMS
This article investigates whether the BNT162b2 vaccine affects anticoagulation control in outpatients using vitamin K antagonists (VKAs).
METHODS
A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. International normalized ratio (INR) results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination.
RESULTS
A total of 3,148 outpatient VKA users were included, with a mean age (standard deviation) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol, and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic (odds ratio [OR] = 1.34 [95% confidence interval [CI] 1.08-1.67]) and subtherapeutic levels (OR = 1.40 [95% CI 1.08-1.83]) after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination (OR = 2.29 [95% CI 1.22-4.28]) and 3.3 times higher after second vaccination (OR = 3.25 [95% CI 1.06-9.97]).
CONCLUSION
BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with VKAs, so it is advisable to monitor the INR shortly after vaccination, even in stable patients.
Topics: Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; BNT162 Vaccine; Blood Coagulation; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Netherlands; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vaccination; Vitamin K
PubMed: 35245945
DOI: 10.1055/s-0042-1742628 -
Cancers Jan 2022Stereotactic radiosurgery (SRS) is a well-established treatment modality for brain metastases (BM). Given the manifold implications of metastatic cancer on the body,...
BACKGROUND
Stereotactic radiosurgery (SRS) is a well-established treatment modality for brain metastases (BM). Given the manifold implications of metastatic cancer on the body, affected patients have an increased risk of comorbidities, such as atrial fibrillation (AF) and venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep-vein thrombosis (DVT). These may require therapeutic anticoagulant therapy (ACT). Limited data are available on the risk of intracranial hemorrhage (ICH) after SRS for patients with BM who are receiving ACT. This bi-institutional analysis aimed to describe the bleeding risk for this patient subgroup.
METHODS
Patients with ACT at the time of single-fraction SRS for BM from two institutions were eligible for analysis. The cumulative incidence of ICH with death as a competing event was assessed during follow-up with magnetic resonance imaging or computed tomography.
RESULTS
Forty-one patients with 97 BM were included in the analyses. The median follow-up was 8.2 months (range: 1.7-77.5 months). The median and mean BM volumes were 0.47 and 1.19 cubic centimeters, respectively. The most common reasons for ACT were PE (41%), AF (34%), and DVT (7%). The ACT was mostly performed utilizing phenprocoumon (37%), novel oral anticoagulants (32%), or low-molecular-weight heparin (20%). Nine BM from a group of five patients with ICH after SRS were identified: none of them caused neurological or any other deficits. The 6-, 12-, and 18-month cumulative bleeding incidences per metastasis were 2.1%, 12.4%, and 12.4%, respectively. The metastases with previous bleeding events and those originating from malignant melanomas were found to more frequently demonstrate ICH after SRS ( = 0.02, = 0.01). No surgical or medical intervention was necessary for ICH management, and no observed death was associated with an ICH.
CONCLUSION
Patients receiving an ACT and single-fraction SRS for small- to medium-sized BM did not seem to have a clinically relevant risk of ICH. Previous bleeding and metastases originating from a malignant melanoma may favor bleeding events after SRS. Further studies are needed to validate our reported findings.
PubMed: 35158734
DOI: 10.3390/cancers14030465 -
The Journal of International Medical... Nov 2021Here, the case of a 92-year-old female patient, who was diagnosed with atrial fibrillation and treated with phenprocoumon (Marcumar®), is reported. Pre-existing...
Here, the case of a 92-year-old female patient, who was diagnosed with atrial fibrillation and treated with phenprocoumon (Marcumar®), is reported. Pre-existing comorbidities were arterial hypertension, coronary heart disease, diabetes mellitus type 2, mild senile dementia and renal insufficiency. Despite treatment with phenprocoumon (Marcumar®), the patient experienced an ischaemic stroke. Her measured international normalized ratio (INR)-values during the months before the stroke were within the therapeutic range of 2-3, then suddenly decreased to 1.25. A retrospective inquiry failed to identify any significant changes in behaviour or therapy adherence, other than the consumption of 1.5 kg (3.3 lb) of hard-boiled candy liquorice in the days leading up to the stroke. The sudden decrease in INR-values may be explained by the influence of liquorice and its compounds on the pharmacokinetics of phenprocoumon (Marcumar®). In this context, the most important factors are the susceptibility of vitamin K antagonists to nutrition or metabolic irregularities, the influence of liquorice on the function of isoenzymes of the cytochrome P450 family that may lead to reduced bioavailability of phenprocoumon, and the influence of liquorice on peroxisome proliferator-activated receptor alpha transactivation.
Topics: Aged, 80 and over; Anticoagulants; Brain Ischemia; Female; Glycyrrhiza; Humans; International Normalized Ratio; Phenprocoumon; Retrospective Studies; Stroke
PubMed: 34826377
DOI: 10.1177/03000605211049649 -
Pharmaceuticals (Basel, Switzerland) Oct 2021The aim of this study was to compare effects of an individualized with a standardized risk assessment for adverse drug reactions to improve drug treatment with...
Individualized versus Standardized Risk Assessment in Patients at High Risk for Adverse Drug Reactions (The IDrug Randomized Controlled Trial)-Never Change a Running System?
The aim of this study was to compare effects of an individualized with a standardized risk assessment for adverse drug reactions to improve drug treatment with antithrombotic drugs in older adults. A randomized controlled trial was conducted in general practitioner (GP) offices. Patients aged 60 years and older, multi-morbid, taking antithrombotic drugs and at least one additional drug continuously were randomized to individualized and standardized risk assessment groups. Patients were followed up for nine months. A composite endpoint defined as at least one bleeding, thromboembolic event or death reported via a trigger list was used. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. In total, = 340 patients were enrolled from 43 GP offices. Patients in the individualized risk assessment group met the composite endpoint more often than in the standardized group (OR 1.63 [95%CI 1.02-2.63]) with multiple adjustments. The OR was higher in patients on phenprocoumon treatment (OR 1.99 [95%CI 1.05-3.76]), and not significant on DOAC treatment (OR 1.52 [95%CI 0.63-3.69]). Pharmacogenenetic variants of CYP2C9, 2C19 and VKORC1 were not observed to be associated with the composite endpoint. The results of this study may indicate that the time point for implementing individualized risk assessments is of importance.
PubMed: 34681280
DOI: 10.3390/ph14101056 -
Journal Der Deutschen Dermatologischen... Oct 2021We aimed to determine the risk of complications during cutaneous surgery for the perioperative discontinuation in comparison to the continuation of antithrombotic agents... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
We aimed to determine the risk of complications during cutaneous surgery for the perioperative discontinuation in comparison to the continuation of antithrombotic agents and the bridging of vitamin K antagonists with heparin in comparison to their continuation.
METHODS
We conducted a systematic review, searching three databases for eligible studies. Methods followed the Cochrane Handbook. We used RoB 2 and ROBINS-I to assess risk of bias. The quality of evidence was judged (GRADE). Fixed-effect meta-analyses were performed.
RESULTS
Two randomized-controlled trials and 19 prospective cohort studies were included. It is uncertain whether, compared to its discontinuation, continuing acetylsalicylic acid (risk difference (RD) 0.004, 95 % confidence interval (CI) -0.003 to 0.019) perioperatively increases the risk of significant postoperative bleedings (SPB). Compared to its discontinuation, continuing phenprocoumon perioperatively may increase the risk of SPB (RD 0.02, 95 % CI 0.00 to 0.05). Bridging phenprocoumon with heparin perioperatively may increase the risk of SPB when compared to its continuation (RD 0.07, 95 % CI 0.01 to 0.22). No evidence was found regarding bleeding risks for direct oral anticoagulants.
CONCLUSIONS
No clear indications of major risks of bleedings when continuing antithrombotic agents during minor skin surgeries were identified. However, the quality of evidence was very low.
Topics: Anticoagulants; Dermatologic Surgical Procedures; Fibrinolytic Agents; Heparin; Humans; Prospective Studies
PubMed: 34596345
DOI: 10.1111/ddg.14579 -
International Journal of Molecular... Sep 2021Patients with atrial fibrillation and previous ischemic stroke (IS) are at increased risk of cerebrovascular events despite anticoagulation. In these patients, treatment...
Patients with atrial fibrillation and previous ischemic stroke (IS) are at increased risk of cerebrovascular events despite anticoagulation. In these patients, treatment with non-vitamin K oral anticoagulants (NOAC) such as edoxaban reduced the probability and severity of further IS without increasing the risk of major bleeding. However, the detailed protective mechanism of edoxaban has not yet been investigated in a model of ischemia/reperfusion injury. Therefore, in the current study we aimed to assess in a clinically relevant setting whether treatment with edoxaban attenuates stroke severity, and whether edoxaban has an impact on the local cerebral inflammatory response and blood-brain barrier (BBB) function after experimental IS in mice. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in male mice receiving edoxaban, phenprocoumon or vehicle. Infarct volumes, functional outcome and the occurrence of intracerebral hemorrhage were assessed. BBB damage and the extent of local inflammatory response were determined. Treatment with edoxaban significantly reduced infarct volumes and improved neurological outcome and BBB function on day 1 and attenuated brain tissue inflammation. In summary, our study provides evidence that edoxaban might exert its protective effect in human IS by modulating different key steps of IS pathophysiology, but further studies are warranted.
Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Disease Models, Animal; Humans; Infarction, Middle Cerebral Artery; Inflammation; Mice; Pyridines; Severity of Illness Index; Stroke; Thiazoles
PubMed: 34576055
DOI: 10.3390/ijms22189893 -
BMJ Open Sep 2021Our study aimed to assess the frequency of potentially inappropriate medication (PIM) use (according to three PIM lists) and to examine the association between PIM use... (Observational Study)
Observational Study
Comparison of FORTA, PRISCUS and EU(7)-PIM lists on identifying potentially inappropriate medication and its impact on cognitive function in multimorbid elderly German people in primary care: a multicentre observational study.
OBJECTIVES
Our study aimed to assess the frequency of potentially inappropriate medication (PIM) use (according to three PIM lists) and to examine the association between PIM use and cognitive function among participants in the MultiCare cohort.
DESIGN
MultiCare is conducted as a longitudinal, multicentre, observational cohort study.
SETTING
The MultiCare study is located in eight different study centres in Germany.
PARTICIPANTS
3189 patients (59.3% female).
PRIMARY AND SECONDARY OUTCOME MEASURES
The study had a cross-sectional design using baseline data from the German MultiCare study. Prescribed and over-the-counter drugs were classified using FORTA (Fit fOR The Aged), PRISCUS (Latin for 'time-honoured') and EU(7)-PIM lists. A mixed-effect multivariate linear regression was performed to calculate the association between PIM use patients' cognitive function (measured with (LDST)).
RESULTS
Patients (3189) used 2152 FORTA PIM (mean 0.9±1.03 per patient), 936 PRISCUS PIM (0.3±0.58) and 4311 EU(7)-PIM (1.4±1.29). The most common FORTA PIM was phenprocoumon (13.8%); the most prevalent PRISCUS PIM was amitriptyline (2.8%); the most common EU(7)-PIM was omeprazole (14.0%). The lists rate PIM differently, with an overall overlap of 6.6%. Increasing use of PIM is significantly associated with reduced cognitive function that was detected with a correlation coefficient of -0.60 for FORTA PIM (p=0.002), -0.72 for PRISCUS PIM (p=0.025) and -0.44 for EU(7)-PIM (p=0.005).
CONCLUSION
We identified PIM using FORTA, PRISCUS and EU(7)-PIM lists differently and found that PIM use is associated with cognitive impairment according to LDST, whereby the FORTA list best explained cognitive decline for the German population. These findings are consistent with a negative impact of PIM use on multimorbid elderly patient outcomes.
TRIAL REGISTRATION NUMBER
ISRCTN89818205.
Topics: Aged; Cognition; Cross-Sectional Studies; Female; Humans; Inappropriate Prescribing; Male; Potentially Inappropriate Medication List; Primary Health Care
PubMed: 34535481
DOI: 10.1136/bmjopen-2021-050344 -
Nederlands Tijdschrift Voor Geneeskunde Sep 2021Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent...
Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.
Topics: Acenocoumarol; Anticoagulants; Blood Coagulation; Humans; International Normalized Ratio; Phenprocoumon
PubMed: 34523845
DOI: No ID Found -
Fitoterapia Oct 2021Thrombosis, which seriously endangers human health and life, is the leading cause of morbidity and mortality globally. Antithrombotic drugs can interfere with the... (Review)
Review
Thrombosis, which seriously endangers human health and life, is the leading cause of morbidity and mortality globally. Antithrombotic drugs can interfere with the occurrence and development of thrombotic diseases and play an important role in the treatment of thrombotic diseases. However, unsatisfactory efficacy and serious adverse effects of existing antithrombotic drugs increase the research for new, efficient and safer drugs. Natural and synthetic coumarins have been shown to possess antithrombotic activity, namely, anticoagulation and antiplatelet aggregation. Especially, coumarin-based warfarin, phenprocoumon and cloricromen have long been used in clinical treatment of thrombosis. Coumarin with low toxicity is the privileged structure for developing novel antithrombotic drugs with multiple mechanisms of action. The present review aims to compile current research on the development of coumarins against thrombosis, emphasizing the relationship between their chemical structures and therapeutic effectiveness. It is intended to provide promising ideas for the discovery of novel coumarin derivatives with high antithrombotic activity.
Topics: Coumarins; Fibrinolytic Agents; Humans; Structure-Activity Relationship; Thrombosis
PubMed: 34352355
DOI: 10.1016/j.fitote.2021.104947