Background Selective serotonin reuptake inhibitors (SSRIs) may increase the risk ofmajor bleeding by decreasing platelet function or decreasing vitamin K antagonist(VKA) metabolism via cytochrome... Show moreBackground Selective serotonin reuptake inhibitors (SSRIs) may increase the risk ofmajor bleeding by decreasing platelet function or decreasing vitamin K antagonist(VKA) metabolism via cytochrome P450 (CYP) inhibition. Aims To determine whether SSRIs are associated with major bleeding during VKAtreatment and investigate the possible mechanisms. Methods In this cohort study, information on SSRI use and bleeding complicationswas obtained from patient records of VKAinitiators between 2006 and 2018 from twoanticoagulation clinics. Conditional logistic regression and time-dependent Cox re-gression were used to estimate the effect of SSRIs on a high international normalizedratio (INR >= 5) within 2 months after SSRI initiation and on major bleeding during theentire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9inhibitors. Results A total of 58,918 patients were included, of whom 1,504 were SSRI users.SSRI initiation versus nonuse was associated with a 2.41-fold (95% confidence interval[CI]: 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95% CI: 1.33-7.43)among CYP2C9-inhibiting SSRI users. The adjusted hazard ratio of major bleeding was1.22 (95% CI: 0.99-1.50) in all SSRI users and 1.31 (95% CI: 0.62-2.72) in CYP2C9-inhibiting SSRI users compared with nonusers. Conclusion SSRI use is associated with an increased risk of high INR and might beassociated with major bleeding. The risk of a high INR was slightly more elevated forCYP2C9-inhibiting SSRI users,suggesting theremight bea pharmacokineticinteraction(byCYP2C9 inhibition) next to a pharmacodynamic effect of SSRIs on platelet activation Show less
Background Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low.... Show moreBackground Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low. Objective To examine if pre-switch TTR determines persistence patterns in NVAF patients who are switched from a VKA to DOAC. Patients/Methods Adult NVAF patients from three Dutch anticoagulation clinics who were newly switched from a VKA to DOAC between July 1, 2013 and September 30, 2018 were stratified by pre-switch TTR levels. DOAC prescription records were examined to determine persistence patterns according to a 100-day prescription gap. Cumulative incidences of non-persistence to DOAC were estimated using the cumulative incidence competing risk method. The association of pre-switch TTR levels with DOAC non-persistence was evaluated by Cox regression models. Results A total of 3696 NVAF patients were included, of whom 690 (18.7%) had a pre-switch TTR <= 45%. After switching from VKA to DOAC, 14.0% (95% confidence interval [CI] 11.3-17.0%) of the patients with a pre-switch TTR <= 45% became non-persistent to DOAC within 1 year, while 9.8% (95% CI 8.7-11.0%) did in those with a pre-switch TTR > 45%. In a multivariable model, a pre-switch TTR <= 45% was associated with a higher risk of non-persistence to DOAC (adjusted hazard ratio 1.55, 95% CI 1.22-1.97). Results were similar when using other cut-off points (60% or 70%) to define a low TTR. Conclusion NVAF patients switching from VKA to DOAC due to a low pre-switch TTR saw a worse persistence pattern to DOAC after the switch compared to patients with a high pre-switch TTR. Show less
Background Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low.... Show moreBackground Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low. Objective To examine if pre-switch TTR determines persistence patterns in NVAF patients who are switched from a VKA to DOAC. Patients/Methods Adult NVAF patients from three Dutch anticoagulation clinics who were newly switched from a VKA to DOAC between July 1, 2013 and September 30, 2018 were stratified by pre-switch TTR levels. DOAC prescription records were examined to determine persistence patterns according to a 100-day prescription gap. Cumulative incidences of non-persistence to DOAC were estimated using the cumulative incidence competing risk method. The association of pre-switch TTR levels with DOAC non-persistence was evaluated by Cox regression models. Results A total of 3696 NVAF patients were included, of whom 690 (18.7%) had a pre-switch TTR <= 45%. After switching from VKA to DOAC, 14.0% (95% confidence interval [CI] 11.3-17.0%) of the patients with a pre-switch TTR <= 45% became non-persistent to DOAC within 1 year, while 9.8% (95% CI 8.7-11.0%) did in those with a pre-switch TTR > 45%. In a multivariable model, a pre-switch TTR <= 45% was associated with a higher risk of non-persistence to DOAC (adjusted hazard ratio 1.55, 95% CI 1.22-1.97). Results were similar when using other cut-off points (60% or 70%) to define a low TTR. Conclusion NVAF patients switching from VKA to DOAC due to a low pre-switch TTR saw a worse persistence pattern to DOAC after the switch compared to patients with a high pre-switch TTR. Show less
Camilleri, E.; Rein, N. van; Meer, F.J.M. van der; Nierman, M.C.; Lijfering, W.M.; Cannegieter, S.C.; Dutch COVID Thrombosis Coalition 2021
Background: Coagulopathy has been reported in severely ill patients with coronavirus disease 2019 (COVID-19). It is unclear whether outpatients with COVID-19 who are treated with vitamin K... Show moreBackground: Coagulopathy has been reported in severely ill patients with coronavirus disease 2019 (COVID-19). It is unclear whether outpatients with COVID-19 who are treated with vitamin K antagonists (VKAs) have unstable anticoagulation.Objective: To assess the stability of VKA therapy in patients with COVID-19 through a case-crossover study.Methods: Between February and July 2020, we included patients who tested positive for COVID-19 from two anticoagulant clinics in the Netherlands. We collected international normalized ratios (INRs) determined between 26 weeks before infection and 12 weeks after. Time in therapeutic range (TTR) and the variance growth rate ( VGR) were calculated within patients.Results: Fifty-one patients with COVID-19 (mean age, 84 years) were included, of whom 15 (29%) were men. Mean TTR in the 26 weeks before COVID-19 was 80% (95% confidence interval [CI], 75-85) compared to 59% (95% CI, 51-68) in the 6 weeks after infection. Mean TTR difference was-23% (95% CI, -32 to -14) with a time above therapeutic range of 38% (95% CI, 30-47) in the 6 weeks after infection. The TTR rose again to 79% (95% CI, 69-89) between 6 and 12 weeks after infection. Also, VGR increased, with a mean increase of 4.8 (95% CI, 2.1-7.5) in the 6 weeks after infection. In the 26 weeks before infection, we registered 19 of 641 (3%) of INR >= 5.0 compared with 35 of 247 (14%) in the 6 weeks after (risk ratio, 4.4; 95% CI, 2.7-7.3).Conclusions: COVID-19 is associated with a strong decrease in TTR and in therapeutic stability in patients taking VKAs. Additional monitoring in these patients is advised to maximize therapeutic stability. Show less
Voskamp, P.W.M.; Dekker, F.W.; Rookmaaker, M.B.; Verhaar, M.C.; Bos, W.J.W.; Diepen, M. van; Ocak, G. 2018
