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Predictors for INR-control in a well-managed warfarin treatment setting.

ABSTRACT: Warfarin is well studied in patients with non-valvular atrial fibrillation (AF). It has low complication rates for patients achieving individual Time in Therapeutic Range (iTTR)?>?70%. The risk scores SAMe-TT₂R₂ and PROSPER are designed to predict future TTR, but are derived from a heterogeneous population with generally low iTTR. The aim of this study was to evaluate predictors for high and low iTTR in an AF population in Sweden, where there is a generally good anticoagulation control. A retrospective register study based on Swedish warfarin dosing system AuriculA, including 28,011 AF patients starting treatment during 1 January 2006 to 31 December 2011. Complications and risk factors were analysed and related to iTTR. Mean age was 73.7 (SD?±?9.5) years, with 42.0% women. Mean CHA₂DS₂-VASc score (SD) was 3.6 (±?1.7). For patients with iTTR??70% (3.7% vs. 1.1%). Previous stroke were more prevalent for patients with high than low iTTR (17.1% vs. 20.3%). Concomitant comorbidities were associated with increased risk of poor iTTR. In Swedish AF patients, excessive alcohol use is clearly associated with iTTR below 60%. Patients with previous stroke are more likely to get iTTR above 70%, unlike those with concomitant disorders who more often have poor anticoagulation control. The SAMe-TT₂R₂-score cannot be applied in Sweden.

SUBMITTER: Bjorck F

PROVIDER: S-EPMC6394450 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Predictors for INR-control in a well-managed warfarin treatment setting.

Björck Fredrik F Kadhim Hayder H Själander Anders A

Journal of thrombosis and thrombolysis 20190201 2

Warfarin is well studied in patients with non-valvular atrial fibrillation (AF). It has low complication rates for patients achieving individual Time in Therapeutic Range (iTTR) > 70%. The risk scores SAMe-TT<sub>2</sub>R<sub>2</sub> and PROSPER are designed to predict future TTR, but are derived from a heterogeneous population with generally low iTTR. The aim of this study was to evaluate predictors for high and low iTTR in an AF population in Sweden, where there is a generally good anticoagula ...[more]

PMID: 30411185

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Project description:ObjectivesWarfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3'-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis.Methods133 OAT patients were recruited and assessed for warfarin/3'-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups.ResultsIn the whole OAT group both warfarin and 3'-hydroxywarfarin correlate with INR at comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin weekly dosage better correlates with warfarin than with 3'-hydroxywarfarin (r2 = 0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3'-hydroxywarfarin the correlation strongly increased (r2 = 0.1114; p<0.0001). Interestingly, 3'-hydroxywarfarin reached a strong correlation at c4 respect to warfarin (r2 = 0.2157 and r2 = 0.0549; p = 0.0005 and p = 0.0944 respectively) seeming less affected by drug adjustments in the subgroup of 52 patients who started OAT. The multivariate analyses aimed at estimating the true contribution of 3'-hydroxywarfarin on INR value ascribed it the unique significant value (p = 0.0021) in spite of warfarin who lost association. The pharmacogenetics studies confirmed that patients carrying the VKORC1 variant-allele required lower warfarin maintenance dosage and that the combination of VKORC1 and CYP2C9 yielded a warfarin responsive index (WRI) inversely related to the number variant alleles.ConclusionOur results overall suggest that 3'-hydroxywarfarin monitoring could be of great advantage in INR monitoring respect to classical warfarin assessment showing significant contribution also in multivariate analysis. Therefore, additional active metabolites should be recognized and investigated as novel useful indicators.

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Predictors for INR-control in a well-managed warfarin treatment setting.

Publications

Predictors for INR-control in a well-managed warfarin treatment setting.

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