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Der Chirurg; Zeitschrift Fur Alle... Jul 2021A decreased antiplatelet prophylaxis (low response, LR/high on-treatment platelet reactivity, HPR) with acetylsalicylic acid (ASA) is associated with an increased risk...
BACKGROUND
A decreased antiplatelet prophylaxis (low response, LR/high on-treatment platelet reactivity, HPR) with acetylsalicylic acid (ASA) is associated with an increased risk of thromboembolic events. The prevalence of a LR is frequent with about 20% and a therapeutic regimen is not yet established. The aim of this prospective study was to evaluate the effectiveness of a therapeutic regimen for treatment adaptation when LR/HPR is detected in vascular surgery patients.
METHODS
Overall, 36 patients under long-term antiplatelet treatment with 100 mg/day ASA and a detected ASA low response (ALR) were included in the study. In this patient group a modification of the prophylactic medication was carried out according to the established treatment plan and a control aggregometry was performed. The therapeutic regimen followed the test and treat principle. To evaluate the effect of ASA impedance, aggregometry with multiple electrodes was used (multiplate).
RESULTS
All 36 patients were successfully transferred to response status with the treatment scheme. In 32 (88.89%) patients an increased dose of 300 mg/day ASA was carried out and in 2 (5.56%) patients the medication was changed from ASA to clopidogrel. A further 2 (5.56%) patients were switched to oral anticoagulation with phenprocoumon, due to other indications. Bleeding complications or other side effects did not occur.
CONCLUSION
The chosen treatment regime for a low response proved to be effective and safe in vascular surgery patients. A guideline-compliant increase of the ASA dose from 100 mg to 300 mg/day predominantly led to an effective inhibition of platelet aggregation in the aggregometry.
Topics: Aspirin; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies
PubMed: 32945920
DOI: 10.1007/s00104-020-01280-x -
BMC Medicine Aug 2020Direct oral anticoagulants (DOACs) are not only increasingly being used for the initial stroke prevention therapy but progressively also substitute vitamin K antagonist...
Comparing stroke prevention therapy of direct oral anticoagulants and vitamin K antagonists in patients with atrial fibrillation: a nationwide retrospective observational study.
BACKGROUND
Direct oral anticoagulants (DOACs) are not only increasingly being used for the initial stroke prevention therapy but progressively also substitute vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (AF). DOACs have been compared regarding therapeutic efficacy and adverse outcomes to warfarin in several pivotal studies and showed non-inferiority in terms of stroke prevention and superiority in terms of bleeding complications. However, comprehensive comparative studies are lacking for phenprocoumon, a VKA prescribed frequently outside the USA and the UK and accounting for 99% of all VKA prescriptions in Germany. Patients treated with phenprocoumon seem to meet more often international normalized ratio values in the therapeutic range, which may have implications concerning their efficacy and safety. This study aims at comparing the risk of stroke and bleeding in phenprocoumon- and DOAC-treated patients with AF in an adequately powered observational study population.
METHODS
Retrospective analysis of stroke and bleeding incidence of 837,430 patients (1.27 million patient years) treated with DOAC or phenprocoumon for stroke prevention in German ambulatory care between 2010 and 2017. Relative risks of stroke and bleeding were estimated by calculating cox regression-derived hazard ratios (HR) and 95% confidence intervals (CI) of propensity score-matched cohorts.
RESULTS
Patients treated with DOAC had an overall higher risk for stroke (HR 1.32; CI 1.29-1.35) and a lower risk for bleeding (0.89; 0.88-0.90) compared to phenprocoumon. When analyzed separately, the risk for stroke was higher for dabigatran (1.93; 1.82-2.03), apixaban (1.52; 1.46-1.58), and rivaroxaban (1.13; 1.10-1.17) but not for edoxaban (0.88; 0.74-1.05). The risk for bleeding was lower for dabigatran (0.85; 0.83-0.88), apixaban (0.71; 0.70-0.73), and edoxaban (0.29; 0.17-0.51) but not for rivaroxaban (1.03; 1.01-1.04).
CONCLUSIONS
This study provides a comprehensive view of the stroke and bleeding risks associated with phenprocoumon and DOAC use in Germany. Phenprocoumon may be preferable to DOAC treatment for the prevention of strokes in AF in a real-world population cared for in ambulatory care.
Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Retrospective Studies; Stroke; Vitamin K; Young Adult
PubMed: 32847578
DOI: 10.1186/s12916-020-01695-7 -
PloS One 2020Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability...
BACKGROUND
Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control.
AIMS
We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability.
METHODS AND RESULTS
In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2-3, 269 patients in target range 2-3.5 and 98 patients in target range 2.5-3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers' TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2-3, 2-3.5 and 2.5-3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers' INRs were much more stable than non-switchers'.
CONCLUSION
Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase.
Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Retrospective Studies; Risk; Treatment Outcome; Venous Thromboembolism; Vitamin K
PubMed: 32649714
DOI: 10.1371/journal.pone.0235639 -
Journal of Clinical Medicine Jun 2020Individual differences in required drug dosages exist based on the pharmacogenomic (PGx) profiles. This study aimed to assess associations between PGx profiles and...
Individual differences in required drug dosages exist based on the pharmacogenomic (PGx) profiles. This study aimed to assess associations between PGx profiles and adverse drug reactions (ADR) that lead to admissions to the emergency department (ED). ADR cases of the prospective multi-center observational trial in EDs (ADRED study) were analyzed ( = 776) together with the relevant PGx phenotypes of the enzymes CYP2D6, CYP2C19, CYP2C9, and VKORC1. Overall, the allele frequency distribution in this cohort did not differ from the population frequencies. We compared the frequencies of phenotypes in the subgroups with the drugs suspected of certain ADR, in the remaining cases. The frequency distribution of CYP2C19 differed for the ADR bleeding cases suspected of clopidogrel ( = 0.020). In a logistic regression analysis, higher CYP2C19 activity (OR (95% CI): 4.97 (1.73-14.27)), together with age (1.05 (1.02-1.08)), showed an impact on the clopidogrel-suspecting ADRs, when adjusting for the clinical parameters. There was a trend for an association of phenprocoumon-risk profiles (low VKORC1 or CYP2C9 activity) with phenprocoumon-suspecting ADRs ( = 0.052). The PGx impact on serious ADRs might be highest in drugs that cannot be easily monitored or those that do not provoke mild ADR symptoms very quickly. Therefore, patients that require the intake of those drugs with PGx variability such as clopidogrel, might benefit from PGx testing.
PubMed: 32527038
DOI: 10.3390/jcm9061801 -
Diagnostics (Basel, Switzerland) Jun 2020We report a case of a young male who presented with acute limb ischemia after sport. With no prior history of disease, a non-infective endocarditis of the native aortic...
We report a case of a young male who presented with acute limb ischemia after sport. With no prior history of disease, a non-infective endocarditis of the native aortic valve was diagnosed. After surgical valve replacement, the patient suffered from acute myocardial ischemia under phenprocoumon therapy. Anti-coagulant monitoring was subsequently changed to Factor II analysis after a rare Factor VII deficiency and prothrombin mutation (G20210A) was diagnosed.
PubMed: 32521783
DOI: 10.3390/diagnostics10060384 -
Drugs & Aging Jul 2020Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age... (Review)
Review
A Structured Literature Review and International Consensus Validation of FORTA Labels of Oral Anticoagulants for Long-Term Treatment of Atrial Fibrillation in Older Patients (OAC-FORTA 2019).
INTRODUCTION
Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019.
METHODS
A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA.
RESULTS
A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p < 0.05) and the proposed FORTA classes were confirmed in all cases during the first round (consensus coefficient > 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A.
CONCLUSION
OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age.
Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Consensus Development Conferences as Topic; Dabigatran; Europe; Female; Humans; Long-Term Care; Male; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Vitamin K; Warfarin
PubMed: 32500503
DOI: 10.1007/s40266-020-00771-0 -
Journal of Nuclear Medicine : Official... Jan 2021Proinflammatory macrophages are important mediators of inflammation after myocardial infarction and of allograft injury after heart transplantation. The aim of this...
Proinflammatory macrophages are important mediators of inflammation after myocardial infarction and of allograft injury after heart transplantation. The aim of this study was to image the recruitment of proinflammatory chemokine receptor 2-positive (CCR2+) cells in multiple heart injury models. Cu-DOTA-extracellular loop 1 inverso (ECL1i) PET was used to image CCR2+ monocytes and macrophages in a heart transplantation mouse model. Flow cytometry was performed to characterize CCR2+ cells. Autoradiography on a human heart specimen was conducted to confirm binding specificity. Cu- and Ga-DOTA-ECL1i were compared in an ischemia-reperfusion injury mouse model. Cu-DOTA-ECL1i showed sensitive and specific detection of CCR2+ cells in all tested mouse models, with efficacy comparable to that of Ga-DOTA-ECL1i. Flow cytometry demonstrated specific expression of CCR2 on monocytes and macrophages. The tracer binds to human CCR2. This work establishes the utility of Cu-DOTA-ECL1i to image CCR2+ monocytes and macrophages in mouse models and provides the requisite preclinical information to translate the targeted clinical-grade CCR2 imaging probe for clinical investigation of heart diseases.
Topics: Animals; Heart Injuries; Isotope Labeling; Mice; Mice, Inbred C57BL; Monocytes; Phenprocoumon; Positron-Emission Tomography; Receptors, CCR2
PubMed: 32444372
DOI: 10.2967/jnumed.120.244673 -
Scientific Reports May 2020We examined human exposures to dental products (EDP), stomatological preparations (ESP), and in the context of dental care (EDC) or toothache (ETA) registered by the...
We examined human exposures to dental products (EDP), stomatological preparations (ESP), and in the context of dental care (EDC) or toothache (ETA) registered by the Poisons Information Centre (PIC) Erfurt from 1997 to 2017. Dental products like dental technical and filling materials belong to medical devices. Stomatological preparations were classified according to the ATC code and symptom severity to the Poisoning Severity Score (PSS). In total, 156 cases of EDP (136 cases with different tooth filling materials), 1167 cases of ESP (55.6% fluoride containing products), 979 cases of EDC, and 331 cases of ETA were registered. Symptom severity in EDP and ESP were asymptomatic or mild. In ETA and EDC, however, 35 cases with moderate and 5 cases with severe symptoms were detected. 5 moderate and 3 severe cases were caused by prolonged paracetamol overdose. Severe bleeding occurred following tooth extraction in a 41 year-old phenprocoumon treated patient after self-medication with acetylsalicylic acid and metamizole. Gingival injection of lidocaine plus epinephrine in a 37 year-old healthy woman resulted in severe bradycardia and cardiac arrest. Acute toxicity of EDP and ESP appears to be low. Prolonged paracetamol overdose because of toothache, and some dental treatment can result in severe symptoms.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Dental Care; Dental Materials; Female; Humans; Infant; Male; Middle Aged; Occupational Exposure; Toothache; Young Adult
PubMed: 32415116
DOI: 10.1038/s41598-020-65079-w -
European Journal of Case Reports in... 2020We present a case of an 85-year-old woman diagnosed with uncomplicated pyelonephritis, who was treated with intravenous ceftriaxone. Her chronic medications were...
UNLABELLED
We present a case of an 85-year-old woman diagnosed with uncomplicated pyelonephritis, who was treated with intravenous ceftriaxone. Her chronic medications were phenprocoumon, diltiazem and bisoprolol. During the infectious phase, the patient presented tachycardia - despite high-dose beta-blocker treatment - and developed left acute heart failure, with acute renal failure (pre-renal origin). After introduction of furosemide diuretic therapy, clinical conditions improved and better control of the volemic status and heart rate was achieved. Several days after ceftriaxone and digoxin therapy initiation, worsening multiple non-blanching palpable purpuric lesions with bullae and papules, limited to the lower extremities, were noted. Skin biopsy was performed and a diagnosis of leucocytoclastic vasculitis, with associated panniculitis, was made. Ceftriaxone was discontinued and systemic corticosteroids were introduced, with a clear improvement in the cutaneous condition.
LEARNING POINTS
Leucocytoclastic vasculitis is a rare but significant side effect related to the administration of ceftriaxone.The importance of skin biopsy in the differential diagnosis of skin eruptions.
PubMed: 32309253
DOI: 10.12890/2020_001464 -
World Neurosurgery Jul 2020The chronic subdural hematoma (cSDH)-Drain trial compared recurrence rates and clinical outcome associated with the use of subperiosteal drain (SPD) and subdural drain... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The chronic subdural hematoma (cSDH)-Drain trial compared recurrence rates and clinical outcome associated with the use of subperiosteal drain (SPD) and subdural drain (SDD) after burr-hole drainage for cSDH. This subgroup analysis aimed to determine whether one drain type is preferable for patients treated with platelet inhibitors (PI) or anticoagulants (AC).
METHODS
This subanalysis included 133 patients treated with PI/AC of the 220 patients from the preceding cSDH-Drain trial. For these patients the association between the drain type used and recurrence rates, mortality, as well as clinical outcome at 6 weeks and 12 months follow-up were analyzed using a logistic regression analysis model. Additionally, recurrence rates, clinical outcome, and mortality were assessed for each PI or AC type separately.
RESULTS
The insertion of SPD was associated with 7.35% recurrence rates compared to 13.85% with SDD in patients treated with PI or AC (OR 0.41, 95% CI 0.06-2.65, P = 0.36). Outcome measurements and mortality did not differ significantly between both groups at 6-week and 12-month follow-up. In addition, there was no statistically significant association between drain type and recurrence rate or mortality when comparing data for each PI or AC type. At 24 hours postoperatively, significantly more patients under phenprocoumon and natrium-dalteparin had a Glasgow Coma Scale score between 13 and 15 in the SDD group compared with the SPD group (P = 0.006), whereaas at 6-week follow-up significantly more patients in the SDD group treated with ASA had a good modified Rankin scale score (P = 0.01). At 12 months, no significant difference in outcome measurements was seen for all PI and AC types.
CONCLUSIONS
In patients treated with PI or AC, the insertion of SPD after burr-hole drainage of cSDH showed comparable recurrence, mortality, and long term outcome rates when compared with SDD.
Topics: Aged; Aged, 80 and over; Anticoagulants; Drainage; Female; Hematoma, Subdural, Chronic; Humans; Male; Periosteum; Platelet Aggregation Inhibitors; Recurrence; Subdural Space; Treatment Outcome; Trephining
PubMed: 32247794
DOI: 10.1016/j.wneu.2020.03.134