Direct oral anticoagulants (DOACs) are increasingly used and are an important cornerstone in antithrombotic therapy. Adverse drug reactions (ADRs) such as bleedings have only partially been investigated during clinical trials. The primary goal was to analyse pharmacovigilance data based on spontaneous reports of gastrointestinal (GI) bleedings with DOACs reported to EudraVigilance. A second goal was to compare GI safety profiles between DOACs based on these signals. All DOAC related GI bleedings mentioned in individual case safety reports (ICSRs) from 2012 till 2017 in the European Economic Area were classified in four GI categories based on the reported site of occurrence of the haemorrhage. Age group and gender of the patient, seriousness and ADR outcome, and the reporter's qualification were assessed per category and per DOAC. Disproportionality analyses were performed to evaluate whether or not the reported ADRs were more prevalent with a given DOAC. ICSRs were bleeding-related in about half of the cases (n = 28,992/53,471). Of these bleedings, >25% was GI-related. Most patients experiencing GI bleedings were between 65 and 85 years old, with no obvious differences between men and women. Stomach, ulcer-related duodenal, and rectal bleedings were the most reported GI bleedings with a fatal outcome in 5.8%, 7.5%, and 9.8% of the cases for rivaroxaban, apixaban, and dabigatran, respectively. The disproportionality data suggest that dabigatran is more frequently involved in GI bleeding events than the other DOACs. DOACs were significantly associated with GI bleedings. Although the data should be interpreted with caution, it seems that dabigatran was associated more often than other DOACs with GI bleedings based on the analysis of spontaneous pharmacovigilance reports.
- MeSH
- antikoagulancia škodlivé účinky MeSH
- aplikace orální MeSH
- cévní mozková příhoda * farmakoterapie MeSH
- dabigatran škodlivé účinky MeSH
- fibrilace síní * farmakoterapie MeSH
- gastrointestinální krvácení chemicky indukované epidemiologie farmakoterapie MeSH
- lidé MeSH
- retrospektivní studie MeSH
- rivaroxaban škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: To analyse whether the benefits and risks of rivaroxaban plus aspirin vary in patients with comorbidities and receiving multiple drugs. In patients with coronary or peripheral artery disease, adding low-dose rivaroxaban to aspirin reduces cardiovascular events and mortality. Polypharmacy and multimorbidity are frequent in such patients. METHODS AND RESULTS: We describe ischaemic events (cardiovascular death, stroke, or myocardial infarction) and major bleeding in participants from the randomized, double-blind COMPASS study by number of cardiovascular medications and concomitant medical conditions. We compared event rates and hazard ratios (HRs) for rivaroxaban plus aspirin vs. aspirin alone by the number of medications and concomitant conditions, and tested for interaction between polypharmacy or multimorbidity and the antithrombotic regimen. The risk of ischaemic events was higher in patients with more concomitant drugs (HR 1.7, 95% confidence interval 1.5-2.1 for >4 vs. 0-2) and with more comorbidities (HR 2.3, 1.8-2.1 for >3 vs. 0-1). Multimorbidity, but not polypharmacy, was associated with a higher risk of major bleeding. The relative efficacy, safety, and net clinical benefit of rivaroxaban were not affected by the number of drugs or comorbidities. Patients taking more concomitant medications derived the largest absolute reduction in the net clinical outcome with added rivaroxaban (1.1% vs. 0.4% reduction with >4 vs. 0-2 cardiovascular drugs, number needed to treat 91 vs. 250). CONCLUSION: Adding low-dose rivaroxaban to aspirin resulted in benefits irrespective of the number of concomitant drugs or comorbidities. Multiple comorbidities and/or polypharmacy should not dissuade the addition of rivaroxaban to aspirin in otherwise eligible patients.
Prevalencia fibrilácie predsiení a diabetes mellitus je na vzostupe a tieto ochorenia sa často vyskytujú spoločne. Diabetes mellitus je nezávislý rizikový faktor ischemickej cievnej mozgovej príhody a systémovej embolizácie u pacientov s fibriláciou predsiení. Taktiež sa zdá, že pacienti s cievnou mozgovou príhodou na podklade fibrilácie predsiení a súčasným diabetes mellitus 2. typu majú horšie výsledky. Intenzívna aktivácia koagulačného systému, znížená fibrinolytická aktivita, zmeny vo funkcii krvných doštičiek a endotelu, sprevádzané zvýšenými hladinami antigénu tkanivového aktivátora plazminogénu a aktivitou faktora VIII, môžu slúžiť ako spojenie medzi diabetes mellitus a ischemickou cievnou mozgovou príhodou súvisiacou s fibriláciou predsiení. Dlhodobá antikoagulácia je indikovaná u väčšiny pacientov s diabetes mellitus a fibriláciou predsiení na prevenciu nežiaducich embolických príhod spojených s fibriláciou predsiení. Tento článok skúma aktuálnu literatúru týkajúcu sa používania rivaroxabanu u jedincov s diabetes mellitus a s fibriláciou predsiení.
The prevalence of atrial fibrillation and diabetes mellitus is rising, and these disorders frequently occur simultaneously. Diabetes mellitus is an independent risk factor of ischemic stroke and systemic embolism in patients with atrial fibrillation. Moreover, patients with atrial fibrillation-associated stroke and concomitant diabetes mellitus seem to have worse outcome compared to non-diabetic patients. Intensive activation of coagulation, decreased fibrinolytic activity, changes in platelet and endothelial function, together with increased levels of tissue plasminogen activator and factor VIII activity might directly link diabetes mellitus with atrial fibrillation-associated stroke. Long-term anticoagulation is indicated in majority of patients with diabetes mellitus and atrial fibrillation to prevent adverse embolic events connected with atrial fibrillation. This article reviews up-to-date literature regarding the use of rivaroxaban in patients with diabetes mellitus and with atrial fibrillation.
- MeSH
- antikoagulancia farmakologie škodlivé účinky terapeutické užití MeSH
- cévní mozková příhoda * prevence a kontrola MeSH
- diabetes mellitus MeSH
- fibrilace síní MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- rivaroxaban * farmakologie škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Autoři předkládají popis průběhu suicidálního pokusu nemocného vyššího věku smíšenou medikací včetně až 12 tablet rivaroxabanu o síle 20 mg. Monitorování aktivity anti Xa ukázalo její opožděný nástup oproti údajům výrobce a dosavadním klinickým zkušenostem. V diskusi jsou rozebrány možnosti ovlivnění farmakokinetiky i farmakodynamiky rivaroxabanu současně požitou další medikací a etanolem.
The authors present a description of the course of a suicidal attempt in an elderly patient with mixed medication, including up to 12 tablets of rivaroxaban with a strength of 20 mg. Monitoring of anti-Xa activity showed its delayed onset compared to the manufacturer‘s data and clinical experience to date. The discussion considers the potential to influence the pharmacokinetics and pharmacodynamics of rivaroxaban with other medications and ethanol used concomitantly.
- Klíčová slova
- farmakodynamika,
- MeSH
- lidé MeSH
- pokus o sebevraždu MeSH
- rivaroxaban * farmakokinetika farmakologie škodlivé účinky MeSH
- senioři nad 80 let MeSH
- výsledek terapie MeSH
- zneužívání léků na předpis * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- Publikační typ
- kazuistiky MeSH
Importance: Prior studies have observed an association between the burden of atherosclerotic vascular disease and the risk of venous thromboembolism (VTE). The association is not well described in peripheral artery disease (PAD) after lower extremity revascularization (LER). Objective: To describe the risk of, factors associated with, and outcomes after VTE, as well as the association of low-dose rivaroxaban plus antiplatelet therapy with VTE after LER. Design, Setting, and Participants: This global, multicenter cohort study used data from the Vascular Outcomes Study of ASA (acetylsalicylic acid) Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER PAD) randomized clinical trial, which enrolled patients from 2015 to 2018 with median follow-up of 28 months. Participants included patients with PAD undergoing LER. Patients with an indication for therapeutic anticoagulation were excluded. Data were analyzed from September 2020 to September 2021. Exposure: Randomization to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily; short-term clopidogrel was used at the discretion of the treating physician. Main Outcomes and Measures: Symptomatic VTE was a prespecified secondary outcome and prospectively collected. Results: Among 6564 patients (median [IQR] age, 67 [61-73] years; 4860 [74.0%] men), 66 patients had at least 1 VTE. The 3-year rate of VTE in patients receiving placebo was 1.7%, and the pattern of risk was linear (year 1: 0.5%; year 2: 1.1%). After multivariable modeling, weight (hazard ratio [HR], 3.04; 95% CI, 1.09-8.43), hypertension (HR, 2.11; 95% CI, 0.91-4.89), prior amputation (HR, 2.07; 95% CI, 0.95-4.53), and older age (HR, 1.81; 95% CI, 1.06-3.11) were associated with increased risk of VTE. VTE was associated with risk of subsequent mortality (HR, 7.22; 95% CI, 4.66-11.19). Compared with aspirin alone, rivaroxaban plus aspirin was associated with lower VTE risk (HR, 0.61; 95% CI, 0.37-0.998; P = .047), with benefit apparent early and sustained over time. This association was not modified by use of clopidogrel at randomization (without clopidogrel: HR, 0.55; 95% CI, 0.29-1.07; with clopidogrel: HR, 0.69; 95% CI, 0.32-1.48; P for interaction = .67). Conclusions and Relevance: In this cohort study, there was continuous risk for VTE after LER in patients with PAD, with greater risk in patients who were older and had obesity and those with more severe PAD, as reflected by prior amputation. Low-dose rivaroxaban plus aspirin was associated with lower VTE risk compared with aspirin alone, with benefits apparent early and continued over time. The spectrum of venous and arterial thrombotic events and overall benefits of more potent antithrombotic strategies for prevention should be considered after LER for PAD.
- MeSH
- Aspirin škodlivé účinky MeSH
- dolní končetina krevní zásobení chirurgie MeSH
- inhibitory agregace trombocytů škodlivé účinky MeSH
- klopidogrel terapeutické užití MeSH
- kohortové studie MeSH
- lidé MeSH
- onemocnění periferních arterií * komplikace epidemiologie chirurgie MeSH
- rivaroxaban škodlivé účinky MeSH
- senioři MeSH
- žilní tromboembolie * epidemiologie etiologie prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: The effect of interventions on functional impairment is an important outcome in stroke prevention trials and should be considered as an adjunct to counting discrete events. In the NAVIGATE-ESUS trial, 7213 patients with recent embolic strokes of undetermined source were randomized to rivaroxaban (15 mg once daily) or aspirin (100 mg daily). After 11 months there was no effect on the prevention of recurrent stroke. AIMS: To determine the effect of rivaroxaban compared to aspirin on functional and cognitive outcomes. METHODS: Function and cognition were measured at baseline, 1 year, and study end using the Standard Assessment of Global Everyday Activities (SAGEA), a 15-item scale assessing cognitive, instrumental, and basic activities of daily living as well as mobility, and the Montreal Cognitive Assessment (MoCA). Changes in scores were calculated by subtracting either study end or 1-year scores from baseline, and differences in distributions were compared using the Mann-Whitney U test. SAGEA and MoCA scores were also correlated with recurrent stroke. RESULTS: Follow-up SAGEA scores were available in 6378 (88%) participants. There was no difference in change in function for those allocated to rivaroxaban compared to aspirin (Mann-Whitney U test, p = 0.8), with both distributions having a median (25p,75p) change of 0 (-2,1). Overall, more of those who experienced a recurrent stroke (n=247; mostly minor ischemic), reported functional difficulty at study end versus entry, compared with those who did not (51% versus 30%, chi-square test, p< 0.001), and this was consistent across global regions. There was no difference in the change in cognition by treatment group, nor were recurrent strokes associated with a change in cognition. CONCLUSIONS: Rivaroxaban, compared to aspirin, was not associated with changes in functional or cognitive status in patients with recent ESUS. The SAGEA scale detected changes in functional status associated with recurrent strokes in an international stroke population.
- MeSH
- Aspirin škodlivé účinky MeSH
- cévní mozková příhoda * diagnóza farmakoterapie etiologie MeSH
- činnosti denního života MeSH
- dvojitá slepá metoda MeSH
- embolická cévní mozková příhoda * MeSH
- inhibitory agregace trombocytů MeSH
- inhibitory faktoru Xa škodlivé účinky MeSH
- intrakraniální embolie * diagnóza farmakoterapie etiologie MeSH
- kognice MeSH
- lidé MeSH
- rivaroxaban škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: In patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 mg once daily compared with aspirin 100 mg once daily. We assessed the effect of switching to non-study aspirin at the time of early stopping. METHODS: Incident composite of myocardial infarction, stroke or cardiovascular death was estimated per 100 person-years (py) during randomised treatment (n=18 278) and after study treatment discontinuation to non-study aspirin (n=14 068). RESULTS: During randomised treatment, the combination compared with aspirin reduced the composite (2.2 vs 2.9/100 py, HR: 0.76, 95% CI 0.66 to 0.86), stroke (0.5 vs 0.8/100 py, HR: 0.58, 95% CI 0.44 to 0.76) and cardiovascular death (0.9 vs 1.2/100 py, HR: 0.78, 95% CI 0.64 to 0.96). During 1.02 years after early stopping, participants originally randomised to the combination compared with those randomised to aspirin had similar rates of the composite (2.1 vs 2.0/100 py, HR: 1.08, 95% CI 0.84 to 1.39) and cardiovascular death (1.0 vs 0.8/100 py, HR: 1.26, 95% CI 0.85 to 1.86) but higher stroke rate (0.7 vs 0.4/100 py, HR: 1.74, 95% CI 1.05 to 2.87) including a significant increase in ischaemic stroke during the first 6 months after switching to non-study aspirin. CONCLUSION: Discontinuing study rivaroxaban and aspirin to non-study aspirin was associated with the loss of cardiovascular benefits and a stroke excess. TRIAL REGISTRATION NUMBER: NCT01776424.
- MeSH
- Aspirin * aplikace a dávkování škodlivé účinky MeSH
- fibrinolytika aplikace a dávkování škodlivé účinky MeSH
- infarkt myokardu * etiologie mortalita prevence a kontrola MeSH
- ischemická cévní mozková příhoda * etiologie mortalita prevence a kontrola MeSH
- kombinovaná farmakoterapie metody MeSH
- koronární nemoc * diagnóza farmakoterapie MeSH
- lidé MeSH
- monitorování léčiv metody statistika a číselné údaje MeSH
- mortalita MeSH
- náhrada léků škodlivé účinky MeSH
- nenasazení léčby statistika a číselné údaje MeSH
- onemocnění periferních arterií * diagnóza farmakoterapie MeSH
- rivaroxaban * aplikace a dávkování škodlivé účinky MeSH
- senioři MeSH
- trvání terapie MeSH
- výsledky a postupy - zhodnocení (zdravotní péče) MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
AIMS: Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease. METHODS AND RESULTS: We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8-2.6) and cardiovascular death (hazard ratio 2.0; 1.5-2.7) were more than twofold higher in patients with 4-6 compared with 0-1 risk factors (p < 0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors (p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors. CONCLUSION: More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events.
- MeSH
- antikoagulancia aplikace a dávkování škodlivé účinky MeSH
- Aspirin aplikace a dávkování škodlivé účinky MeSH
- časové faktory MeSH
- chronická nemoc MeSH
- dvojitá slepá metoda MeSH
- fibrinolytika aplikace a dávkování škodlivé účinky MeSH
- hodnocení rizik MeSH
- inhibitory faktoru Xa aplikace a dávkování škodlivé účinky MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci koronárních tepen diagnostické zobrazování farmakoterapie mortalita MeSH
- onemocnění periferních arterií diagnostické zobrazování farmakoterapie mortalita MeSH
- prospektivní studie MeSH
- recidiva MeSH
- rivaroxaban aplikace a dávkování škodlivé účinky MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- sekundární prevence * MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Článek podává přehled o novém antidotu přímých perorálních inhibitorů FXa apixabanu a rivaroxabanu, kterým je andexanet alfa (přípravek Ondexxya®). Uvedeny jsou také výsledky uskutečněných klinických studií fáze I–III/VI a dávkování andexanetu alfa při život ohrožujícím krvácení.
A review of a new antidote for direct oral inhibitors of FXa, apixaban and rivaroxaban, andexanet alfa (Ondexxya®), has been reviewed. The results of ongoing phase I–III/VI clinical trials are presented with its dosage for the life‑threatening bleeding.
- Klíčová slova
- andexanet alfa, apixaban, ANNEXA-4,
- MeSH
- antidota * aplikace a dávkování ekonomika farmakokinetika farmakologie škodlivé účinky MeSH
- hemostáza účinky léků MeSH
- inhibitory faktoru Xa * škodlivé účinky MeSH
- klinická studie jako téma MeSH
- krvácení chemicky indukované farmakoterapie klasifikace MeSH
- lidé MeSH
- rekombinantní proteiny aplikace a dávkování ekonomika farmakokinetika farmakologie škodlivé účinky MeSH
- rivaroxaban škodlivé účinky MeSH
- statistika jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
