-
British Journal of Clinical Pharmacology Mar 2018Information on utilization of oral anticoagulants (OACs) in nursing homes is scarce. This study aimed to (i) describe OAC use in German nursing home residents, (ii)...
AIMS
Information on utilization of oral anticoagulants (OACs) in nursing homes is scarce. This study aimed to (i) describe OAC use in German nursing home residents, (ii) examine factors influencing whether treatment is initiated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) and (iii) assess which conditions predict switching to NOAC instead of continuing VKA.
METHODS
Using claims data (2010-2014), we studied a cohort of new nursing home residents aged ≥65 years receiving OAC. Further, OAC use in patients with atrial fibrillation (AF) was examined over the years.
RESULTS
Overall, 16 804 patients (median age: 85 years, 75% female, 44% with renal disease) were included. The majority received phenprocoumon as first OAC (58.0%), followed by rivaroxaban (28.1%). Over the study period, NOAC use increased substantially. Initiating NOAC instead of VKA was predicted by a previous stroke (adjusted odds ratio: 1.76; 95% confidence interval: 1.49-2.08). In contrast, renal disease predicted VKA initiation (0.66; 0.59-0.75) as did the presence of a prosthetic heart valve. Switching from VKA to NOAC was predicted by a stroke (2.55; 2.00-3.24), bleeding events and a recent hospitalization. During 2010-2014, the proportion of AF patients with a CHADS2 score ≥2 receiving OAC increased from 27% to 46%.
CONCLUSIONS
NOACs are increasingly used in German nursing homes, both for initial anticoagulation but also in VKA pre-treated patients. Switching from VKA to NOAC was substantially influenced by aspects such as intended higher effectiveness and safety but probably also practicability due to less blood monitoring.
Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Drug Monitoring; Female; Germany; Hemorrhage; Humans; Kidney Diseases; Male; Nursing Homes; Phenprocoumon; Rivaroxaban; Stroke; Vitamin K
PubMed: 29148592
DOI: 10.1111/bcp.13474 -
Journal of Thrombosis and Haemostasis :... Jan 2018Essentials The knowledge of quality and safety of acenocoumarol and phenprocoumon use in children is limited. We used data from a multicenter retrospective follow-up...
UNLABELLED
Essentials The knowledge of quality and safety of acenocoumarol and phenprocoumon use in children is limited. We used data from a multicenter retrospective follow-up study in children in the Netherlands. The quality of anticoagulation control in the first month of use was low, but improved thereafter. No thromboembolic events occurred, however bleeding events occurred in 1-3 out of 10 patients.
SUMMARY
Background The use of vitamin-K antagonists in pediatric patients is rare and information on the quality and safety of treatment with acenocoumarol and phenprocoumon is limited. Objectives To assess the quality, safety and effectiveness during the first year of acenocoumarol and phenprocoumon treatment in pediatric patients in the Netherlands. Methods The Children Anticoagulation and Pharmacogenetics Study (CAPS) was designed as a multicenter retrospective follow-up study. Patients who used acenocoumarol or phenprocoumon at an age of ≤ 18 years, were selected from four pediatric hospitals and one anticoagulation clinic in the Netherlands. The quality of treatment was assessed by calculating the percentage of time in therapeutic INR range (TTR) for the first month and for every 3 months of use during the first year of treatment. Effectiveness and safety were assessed by the number of thromboembolic and bleeding events. Results In total, 213 patients participated, of whom 187 (155 acenocoumarol; 32 phenprocoumon) were included in this analysis. The mean TTR was 47.0% and 51.4% in the first month of use for acenocoumarol and phenprocoumon, respectively. After the first 3 months the mean TTR for both VKAs was above 64%. In 14.6% (acenocoumarol) and 31.3% (phenprocoumon) of the patients a bleeding event occurred during the first year of treatment; no thromboembolic events were reported. Conclusions The quality of anticoagulation treatment was low during the first month of use and leaves room for improvement. After the first month it increased to an acceptable level. However, bleeding events occurred frequently during the first year.
Topics: Acenocoumarol; Administration, Oral; Adolescent; Age Factors; Anticoagulants; Blood Coagulation; Child; Child, Preschool; Drug Monitoring; Female; Guideline Adherence; Hemorrhage; Humans; Infant; International Normalized Ratio; Male; Netherlands; Phenprocoumon; Practice Guidelines as Topic; Practice Patterns, Physicians'; Quality Indicators, Health Care; Retrospective Studies; Thromboembolism; Time Factors; Treatment Outcome
PubMed: 29108090
DOI: 10.1111/jth.13897 -
BMJ Case Reports Oct 2017A 59-year-old male patient suffered three life-threatening instent thromboses after an initial resuscitation due to an ST-segment elevation myocardial infarction of the...
A 59-year-old male patient suffered three life-threatening instent thromboses after an initial resuscitation due to an ST-segment elevation myocardial infarction of the anterior cardiac wall. With a high-risk profile for heparin-induced thrombocytopenia (HIT), he was placed on argatroban after the second reinfarction. Under this apparently appropriate treatment, a third reinfarction occurred, and the patient had to undergo high-risk cardiac bypass surgery. Later on, a deep vein thrombosis and an intracardiac thrombus formed. Despite a positive screening test for HIT and a single positive result in the heparin-induced platelet aggregation test, we are not convinced that HIT was the only underlying cause for this 'catastrophic thrombotic syndrome'. We speculate that a massive generation of thrombin, reflected in consistently high D dimers and the need of copious amounts of a direct thrombin inhibitor, triggered the set of events. With this case report, we want to raise awareness for cardiac complications in patients with complex clotting disorders and share our experience in the diagnostic and therapeutic management of such an unusual scenario.
Topics: Anticoagulants; Antithrombins; Arginine; Awareness; Blood Coagulation Tests; Coronary Artery Bypass; Heparin; Humans; Male; Middle Aged; Phenprocoumon; Pipecolic Acids; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Sulfonamides; Thrombocytopenia; Thrombosis; Treatment Outcome; Ultrasonography; Venous Thrombosis
PubMed: 29066639
DOI: 10.1136/bcr-2017-221194 -
Clinical Cardiology Nov 2017Data are limited on the safety of periprocedural anticoagulation with novel oral anticoagulants (NOACs) in patients undergoing pulmonary vein isolation (PVI) using the... (Comparative Study)
Comparative Study
BACKGROUND
Data are limited on the safety of periprocedural anticoagulation with novel oral anticoagulants (NOACs) in patients undergoing pulmonary vein isolation (PVI) using the second-generation cryoballoon (CB) for the treatment of atrial fibrillation.
HYPOTHESIS
We hypothesized that the incidence of acute periprocedural complications in patients undergoing PVI do not differ between patients treated with VKA compared to NOACs.
METHODS
In 200 consecutive patients (mean age, 64.3 _ 10.6 years; female, n = 83) with symptomatic atrial fibrillation, PVI using the second-generation 28-mm CB was performed. In patients treated with NOACs, the medication was stopped the day of the procedure and continued the evening after the procedure with a reduced dosage. Patients treated with phenprocoumon were continued on uninterrupted phenprocoumon with a target INR of 2 to 3. If INR was <2, bridging with low-molecular-weight heparin was performed.
RESULTS
Forty-seven of 200 patients (23.5%) were treated with a vitamin K antagonist (VKA) and 55 (27.5%) were treated with apixaban, 67 (33.5%) with rivaroxaban, and 31 (15.5%) with dabigatran. Seven (3.5%) major complications occurred in the overall population. Major bleeding complications did not differ significantly between the 2 groups (P = 0.23). One patient taking VKA had a pericardial tamponade at the end of the procedure; 2 patients treated with apixaban developed a groin hematoma requiring surgical intervention. Transient ischemic attack occurred in 1 patient of the apixaban and rivaroxaban group.
CONCLUSIONS
Apixaban, rivaroxaban, and dabigatran, compared with uninterrupted VKA, did not show a higher risk for major bleeding or ischemic complications in patients undergoing PVI using the second-generation CB.
Topics: Administration, Oral; Aged; Antithrombins; Atrial Fibrillation; Cardiac Catheters; Cerebrovascular Disorders; Cryosurgery; Dabigatran; Drug Administration Schedule; Drug Monitoring; Equipment Design; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Postoperative Hemorrhage; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Vitamin K
PubMed: 28846806
DOI: 10.1002/clc.22782 -
Journal of Thrombosis and Haemostasis :... Nov 2017Essentials The long-term effects of VKORC1 and CYP2C9 variants on clinical outcomes remains unclear. We followed 774 patients ≥65 years with venous thromboembolism for...
UNLABELLED
Essentials The long-term effects of VKORC1 and CYP2C9 variants on clinical outcomes remains unclear. We followed 774 patients ≥65 years with venous thromboembolism for a median duration of 30 months. Patients with CYP2C9 variants are at increased risk of death and non-major bleeding. Patients with genetic variants have a slightly lower anticoagulation quality only.
SUMMARY
Background The long-term effect of polymorphisms of the vitamin K-epoxide reductase (VKORC1) and the cytochrome P450 enzyme gene (CYP2C9) on clinical outcomes remains unclear. Objectives We examined the association between CYP2C9/VKORC1 variants and long-term clinical outcomes in a prospective cohort study of elderly patients treated with vitamin K antagonists for venous thromboembolism (VTE). Methods We followed 774 consecutive patients aged ≥ 65 years with acute VTE from nine Swiss hospitals for a median duration of 30 months. The median duration of initial anticoagulant treatment was 9.4 months. The primary outcome was the time to any clinical event (i.e. the composite endpoint of overall mortality, major and non-major bleeding, and recurrent VTE. Results Overall, 604 (78%) patients had a CYP2C9 or VKORC1 variant. Three hundred and thirty-four patients (43.2%) had any clinical event, 119 (15.4%) died, 100 (12.9%) had major and 167 (21.6%) non-major bleeding, and 100 had (12.9%) recurrent VTE. After adjustment, CYP2C9 (but not VKORC1) variants were associated with any clinical event (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.08-1.66), death (HR, 1.74; 95% CI, 1.19-2.52) and clinically relevant non-major bleeding (sub-hazard ratio [SHR], 1.39; 95% CI, 1.02-1.89), but not with major bleeding (SHR, 1.03; 95% CI, 0.69-1.55) or recurrent VTE (SHR, 0.95; 95% CI, 0.62-1.44). Patients with genetic variants had a slightly lower anticoagulation quality. Conclusions CYP2C9 was associated with long-term overall mortality and non-major bleeding. Although genetic variants were associated with a slightly lower anticoagulation quality, there was no relationship between genetic variants and major bleeding or VTE recurrence.
Topics: Age Factors; Aged; Anticoagulants; Blood Coagulation; Cytochrome P-450 CYP2C9; Female; Hemorrhage; Humans; Male; Pharmacogenetics; Pharmacogenomic Variants; Prospective Studies; Recurrence; Risk Factors; Switzerland; Time Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K; Vitamin K Epoxide Reductases
PubMed: 28834238
DOI: 10.1111/jth.13810 -
Clinical Otolaryngology : Official... Feb 2018Treatment of epistaxis in patients on anticoagulants is challenging and associated with higher admission rates and longer hospital stays compared with patients without... (Comparative Study)
Comparative Study
OBJECTIVES
Treatment of epistaxis in patients on anticoagulants is challenging and associated with higher admission rates and longer hospital stays compared with patients without anticoagulation. However, there is little information about epistaxis in patients taking new direct oral anticoagulants such as rivaroxaban compared with patients on traditional vitamin K antagonists such as phenprocoumon.
DESIGN
Retrospective cohort study.
SETTING
The study was conducted at the emergency department of the University Hospital Inselspital, Bern, Switzerland.
PARTICIPANTS
All admissions to the emergency department of the University Hospital Inselspital, Bern, Switzerland from 1st July 2012 to 30th June 2016 with non-traumatic epistaxis on anticoagulant therapy with phenprocoumon or rivaroxaban were included.
MAIN OUTCOME MEASURES
We compared clinical outcome parameters (admission rates, length of hospital stay and mortality) for both anticoagulant groups.
RESULTS
We included 440 patients with epistaxis, 123 (28%) on rivaroxaban and 317 (72%) on phenprocoumon. Fewer hospital admissions and shorter hospital stays were found in patients under rivaroxaban (12 (10.4%) vs 57 (18.0%) patients, P=.033; 0.7±2.2 vs 1.5±3.7 days, P=.011) compared with phenprocoumon. Anterior epistaxis was more common in the rivaroxaban group in contrast to posterior epistaxis in patients on phenprocoumon (74 (60.2%) vs 139 (43.8%) patients, P=.002; 7 (5.7%) vs 39 (12.3%) patients, P=.042).
CONCLUSIONS
Our data suggests that epistaxis on direct oral anticoagulation with rivaroxaban is associated with shorter hospital stays and fewer hospital admissions than epistaxis on vitamin K antagonist phenprocoumon.
Topics: Aged; Anticoagulants; Epistaxis; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Length of Stay; Male; Patient Admission; Phenprocoumon; Retrospective Studies; Risk Assessment; Rivaroxaban; Switzerland
PubMed: 28510336
DOI: 10.1111/coa.12904 -
Circulation. Heart Failure May 2017Left ventricular assist device-supported patients are usually anticoagulated with a combination of aspirin and vitamin K antagonists. Long-term vitamin K antagonist... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Left ventricular assist device-supported patients are usually anticoagulated with a combination of aspirin and vitamin K antagonists. Long-term vitamin K antagonist therapy can be complicated by unstable international normalized ratio values and patient-related compliance problems. Therefore, direct thrombin inhibitors may represent an alternative to vitamin K antagonists.
METHODS AND RESULTS
Thirty HeartWare ventricular assist device patients with stable renal function were planned for this prospective, randomized, open-label, single-center study. Patients were randomized to receive either phenprocoumon or dabigatran in addition to aspirin for long-term anticoagulation. Treatment duration was scheduled for 1 year and stopped after observation of a primary end point. Dabigatran dose was 110 and 75 mg BID in patients with normal or impaired renal function (glomerular filtration rate >80 mL/min or between 80 and 30 mL/min, respectively). The study was stopped prematurely for safety reasons after 16 patients (61±8 years, 1 female) were randomized. Thromboembolic events occurred in 4 subjects receiving dabigatran (50%) and in 1 receiving phenprocoumon (13%; =0.28). No major bleeding was recorded, and no patient died during the study. Median time to treatment termination was significantly shorter in dabigatran patients (8.5 versus 12.0 months; =0.015).
CONCLUSIONS
Thromboembolic events on dabigatran led to early termination of a randomized controlled trial of dabigatran versus phenprocoumon in left ventricular assist device patients.
CLINICAL TRIAL REGISTRATION
https://www.clinicaltrials.gov. Unique identifier: NCT02872649.
Topics: Antithrombins; Dabigatran; Dose-Response Relationship, Drug; Equipment Failure; Female; Follow-Up Studies; Heart Ventricles; Heart-Assist Devices; Humans; Male; Middle Aged; Phenprocoumon; Pilot Projects; Prospective Studies; Thromboembolism; Time Factors; United States; Vitamin K
PubMed: 28500254
DOI: 10.1161/CIRCHEARTFAILURE.116.003709 -
Drugs & Aging Jul 2017Age appropriateness of anticoagulants for stroke prevention in atrial fibrillation is uncertain. (Review)
Review
Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial Fibrillation in Older People: Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016).
BACKGROUND
Age appropriateness of anticoagulants for stroke prevention in atrial fibrillation is uncertain.
OBJECTIVE
To review oral anticoagulants for the treatment of atrial fibrillation in older (age >65 years) people and to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability using the Fit-fOR-The-Aged (FORTA) classification.
METHODS
We performed a structured comprehensive review of controlled clinical trials and summaries of individual product characteristics to assess study and total patient numbers, quality of major outcome data and data of geriatric relevance. The resulting evidence was discussed in a round table with an interdisciplinary panel of ten European experts. Decisions on age appropriateness were made using a Delphi process.
RESULTS
For the eight drugs included, 380 citations were identified. The primary outcome results were reported in 32 clinical trials with explicit and relevant data on older people. Though over 24,000 patients aged >75/80 years were studied for warfarin, data on geriatric syndromes were rare (two studies reporting on frailty/falls/mental status) and missing for all other compounds. Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist oral anticoagulants (including low/high-intensity dabigatran and high-intensity edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon, acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting the absence of data.
CONCLUSIONS
All non-vitamin K antagonist oral anticoagulants and warfarin were classified as beneficial or very beneficial in older persons (FORTA-A or -B), underlining the overall positive assessment of the risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally used in Europe, the lack of evidence should challenge current practice.
Topics: Administration, Oral; Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Consensus; Dabigatran; Delphi Technique; Europe; Evidence-Based Practice; Female; Humans; Long-Term Care; Middle Aged; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Stroke; Thiazoles; Warfarin
PubMed: 28493216
DOI: 10.1007/s40266-017-0466-6 -
Europace : European Pacing,... Apr 2018Several studies showed reduced stroke severity in patients with atrial fibrillation (AF) if the international normalized ratio (INR) was ≥ 2 at stroke onset. There... (Comparative Study)
Comparative Study Observational Study
AIMS
Several studies showed reduced stroke severity in patients with atrial fibrillation (AF) if the international normalized ratio (INR) was ≥ 2 at stroke onset. There are no respective data for non-vitamin K-dependent oral anticoagulants (NOACs). The aim of this study was to compare the impact of NOAC or phenprocoumon intake on stroke severity.
METHODS AND RESULTS
In this single-centre observational study, 3669 patients with acute ischaemic stroke were retrospectively analysed regarding AF status and medication immediately before admission. Using multivariable regression, we analysed the association of pre-admission anticoagulation with severe stroke (National Institutes of Health Stroke Scale score ≥ 11) on admission and poor outcome at discharge (modified Rankin scale score > 2). Before the index stroke, 655 patients had known AF and a CHA2DS2-VASc score ≥ 2. While 325 (49.6%) patients were anticoagulated, 159 (24.3%) were prescribed a NOAC and 75 (11.5%) phenprocoumon patients had an INR ≥ 2 on admission. Compared with AF patients without medical stroke prevention, an INR ≥ 2 [OR 0.23 (95% CI 0.10-0.53)] or NOAC intake [OR 0.48 (95% CI 0.27-0.86)] were associated with a lower probability of severe stroke after adjustment for confounders, while an INR < 2 [OR 0.62 (95% CI 0.33-1.16)] was not. Adjusted odds ratios for poor functional outcome at hospital discharge were 0.47 (95% CI 0.27-0.84) for NOAC patients, 0.33 (95% CI 0.17-0.65) for INR ≥ 2 and 0.61 (95% CI 0.32-1.16) for INR < 2.
CONCLUSION
NOAC intake before stroke did reduce the probability of severe stroke on hospital admission and poor functional outcome at hospital discharge as similarly demonstrated for phenprocoumon patients with an INR ≥ 2 on admission.
Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Hospitalization; Humans; International Normalized Ratio; Male; Phenprocoumon; Protective Factors; Retrospective Studies; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome
PubMed: 28460024
DOI: 10.1093/europace/eux087 -
EuroIntervention : Journal of EuroPCR... Apr 2017We aimed to assess the efficacy and safety of vitamin K antagonist (VKA) monotherapy in atrial fibrillation (AF) patients undergoing transcatheter aortic valve...
AIMS
We aimed to assess the efficacy and safety of vitamin K antagonist (VKA) monotherapy in atrial fibrillation (AF) patients undergoing transcatheter aortic valve implantation (TAVI).
METHODS AND RESULTS
In 735 TAVIs since 2008 we identified 167 patients suffering from concomitant AF who received either VKA monotherapy (n=77), VKA plus single antiplatelet therapy (SAPT, n=41) or a triple anticoagulation regimen (n=49). Thromboembolic as well as bleeding complications were analysed for six months after TAVI. Only one minor bleeding and no thromboembolic events occurred after VKA therapy had been initiated post TAVI. Compared to patients being treated with additional either single or dual antiplatelet therapy, the incidence of major/life-threatening bleeding complications was significantly lower in the VKA mono group (0/77 [VKA mono] vs. 3/41 [VKA+SAPT; p=0.04] vs. 4/49 [triple anticoagulation; p=0.02]). Analysis of a combined endpoint of post-procedural death, stroke, embolism and major bleeding revealed a significant superiority of VKA monotherapy compared to VKA plus SAPT or DAPT, respectively (5/77 vs. 9/41 [p=0.02] vs. 14/49 [p=0.002]).
CONCLUSIONS
VKA therapy without additional antiplatelet treatment is effective and safe in AF patients undergoing TAVI.
Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Feasibility Studies; Female; Germany; Hemorrhage; Humans; Male; Phenprocoumon; Postoperative Complications; Thromboembolism; Transcatheter Aortic Valve Replacement
PubMed: 28433958
DOI: 10.4244/EIJ-D-15-00259