Use of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Lesions

Biase, Luigi Di

doi:10.1161/jaha.115.002776

Cited by 59 publications

(45 citation statements)

References 53 publications

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“…22, 23 Although recent guidelines recommend using NOACs for non-valvular atrial fibrillation, current research is focused on identifying other potential roles in clinical conditions such as atrial fibrillation associated with valvular heart disease and patients with prosthetic heart valves. 24 Thus, it is possible that the range of indications for NOAC use will expand in the future. 25 …”

Section: Discussionmentioning

confidence: 99%

Restarting Anticoagulant Therapy After Intracranial Hemorrhage

Murthy

Gupta

Merkler

et al. 2017

Stroke

181

133

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Background and Purpose The safety and efficacy of restarting anticoagulation (AC) therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to summarize the associations of AC resumption with the subsequent risk of ICH recurrence and thromboembolism. Method We searched published medical literature to identify cohort studies involving adults with anticoagulation-associated ICH. Our predictor variable was resumption of AC. Outcome measures were thromboembolic events (stroke and/or myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between AC resumption and our outcomes. Results Eight studies were eligible for inclusion in the meta-analysis, with 5,306 ICH patients. Almost all studies evaluated AC with vitamin-K antagonists. Reinitiation of AC was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, [CI], 0.25-0.45; Q = 5.12, P for heterogeneity = 0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of AC therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% CI, 0.58-1.77; Q = 24.68, P for heterogeneity <0.001). No significant publication bias was detected in our analyses. Conclusions In observational studies, reinstitution of AC after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk-benefit profile of AC resumption after ICH.

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Section: Discussionmentioning

confidence: 99%

Restarting Anticoagulant Therapy After Intracranial Hemorrhage

Murthy

Gupta

Merkler

et al. 2017

Stroke

181

133

View full text Add to dashboard Cite

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“…[1] VKAs are highly effective but they have a narrow therapeutic index and they require routine monitoring of the International Normalized Ratio (INR). Over recent years, the oral anticoagulant (OAC) therapy scenario has changed as a result of the introduction of direct oral anticoagulants (DOAcs) [2,3] and improvements in OAC management with VKAs, including pharmacogenetic (PGx) studies, focused on identifying genetic determinants affecting VKA dose requirements. [4–6] The best-characterized genes involved in VKA PGx are vitamin K epoxide reductase complex subunit 1 ( VKORC1 ) and cytochrome P450 2C9 ( CYP2C9 ).…”

Section: Introductionmentioning

confidence: 99%

VKORC1 and CYP2C9 polymorphisms related to adverse events in case-control cohort of anticoagulated patients

et al. 2016

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Vitamin K antagonists (VKAs) are highly effective but have a narrow therapeutic index and require routine monitoring of the INR. The primary aim of pharmacogenetics (PGx) is to optimize patient care, achieving drug treatments that are personalized according to the genetic profile of each patient. The best-characterized genes involved in VKA PGx involve pharmacokinetics (VKORC1) and pharmacodynamics (CYP2C9) of VKA metabolism. The role of these genes in clinical outcomes (bleeding and thrombosis) during oral anticoagulant (OAC) therapy is controversial. The aim of the present study was to evaluate any potential association between genotype VKORC1 and CYP2C9 and adverse events (hemorrhagic and/or thrombotic), during initiation and long-term VKA treatment, in Caucasian patients. Furthermore, we aimed to determine if the concomitant prescription of other selected drugs affected the association between genotype and adverse events.We performed a retrospective, matched case-control study to determine associations between multiple gene variants, drug intake, and any major adverse effects in anticoagulated patients, monitored in 2 Italian anticoagulation clinics.Our results show that anticoagulated patients have a high risk of adverse events if they are carriers of 1 or more genetic polymorphisms in the VKORC1 (rs9923231) and CYP2C9 (rs1799853 and rs1057910) genes.Information on CYP2C9 and VKORC1 variants may be useful to identify individualized oral anticoagulant treatment for each patient, improve management and quality of VKA anticoagulation control, and monitor drug surveillance in pharmacovigilance programs.

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“…The study inclusion criteria were designed to identify a set of AF patients for whom the warfarin‐or‐DOAC question was most applicable (no prior warfarin use, nonvalvular AF). Unfortunately, there is no universally accepted definition of nonvalvular AF that could be applied, and indeed, the 4 major DOAC trials applied slightly different definitions in their respective trials . A previously developed prediction model, the SAMe‐TT 2 R 2 score, was developed with the same intent, though it did not focus specifically on new AF diagnoses .…”

Section: Discussionmentioning

confidence: 99%

Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in Newly Diagnosed Atrial Fibrillation

Williams

Evans

Honushefsky

et al. 2017

JAHA

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BackgroundThough warfarin has historically been the primary oral anticoagulant for stroke prevention in newly diagnosed atrial fibrillation (AF), several new direct oral anticoagulants may be preferred when anticoagulation control with warfarin is expected to be poor. This study developed a prediction model for time in therapeutic range (TTR) among newly diagnosed AF patients on newly initiated warfarin as a tool to assist decision making between warfarin and direct oral anticoagulants.Methods and ResultsThis electronic medical record–based, retrospective study included newly diagnosed, nonvalvular AF patients with no recent warfarin exposure receiving primary care services through a large healthcare system in rural Pennsylvania. TTR was estimated as the percentage of time international normalized ratio measurements were between 2.0 and 3.0 during the first year following warfarin initiation. Candidate predictors of TTR were chosen from data elements collected during usual clinical care. A TTR prediction model was developed and temporally validated and its predictive performance was compared with the SAMe‐TT 2R2 score (sex, age, medical history, treatment, tobacco, race) using R 2 and c‐statistics. A total of 7877 newly diagnosed AF patients met study inclusion criteria. Median (interquartile range) TTR within the first year of starting warfarin was 51% (32, 67). Of 85 candidate predictors evaluated, 15 were included in the final validated model with an R 2 of 15.4%. The proposed model showed better predictive performance than the SAMe‐TT 2R2 score (R 2=3.0%).ConclusionsThe proposed prediction model may assist decision making on the proper mode of oral anticoagulant among newly diagnosed AF patients. However, predicting TTR on warfarin remains challenging.

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Use of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Lesions

Cited by 59 publications

References 53 publications

Restarting Anticoagulant Therapy After Intracranial Hemorrhage

Restarting Anticoagulant Therapy After Intracranial Hemorrhage

VKORC1 and CYP2C9 polymorphisms related to adverse events in case-control cohort of anticoagulated patients

Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in Newly Diagnosed Atrial Fibrillation

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