Long-term vitamin K antagonists treatment patterns of Non-Valvular Atrial Fibrillation (NVAF): a population-based cohort study

Abstract Whether long-term use of vitamin K antagonists (VKAs) might affect the incidence of cancer is a longstanding hypothesis. We conducted a population-based study including all cancer- and thromboembolism-free patients of our health area; study groups were defined according to chronic anticoagulant use to VKA-exposed and control groups. Cancer incidence and cancer-related and overall mortality was assessed in both groups. 76 008 patients (3231 VKA-exposed and 72 777 control subjects) were followed-up for 8.2 (± 3.2) years. After adjusting for age, sex, and time-to-event, the hazard ratio of newly diagnosed cancer in the exposed group was 0.88 (95% confidence interval [95% CI] 0.80-0.98; P < .015). VKA-exposed patients were less likely to develop prostate cancer, 0.69 (95% CI 0.50-0.97; P = .008). The adjusted hazard ratio for cancer-related and overall mortality was 1.07 (95% CI 0.92-1.24) and 1.12 (95% CI 1.05-1.19), respectively. These results support the hypothesis that anticoagulation might have a protective effect on cancer development, especially prostate cancer.

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The international normalized ratio (INR) as seen in a population of patients with atrial fibrillation and cerebral infarction undergoing long-term treatment with vitamin K antagonists

Current Issues in Pharmacy and Medical Sciences ◽

10.1515/cipms-2015-0087 ◽

2015 ◽

Vol 28 (4) ◽

pp. 269-272

Author(s):

Anna Szczepańska-Szerej ◽

Magdalena Wojtan ◽

Beata Szajnoga

Keyword(s):

Atrial Fibrillation ◽

Cerebral Infarction ◽

Vitamin K ◽

Vitamin K Antagonists ◽

International Normalized Ratio ◽

Blood Parameters ◽

Term Treatment ◽

Adequate Treatment ◽

Long Term Treatment

Abstract It is estimated that nearly 20% of all cerebral infarctions in the total population are the result of a complication of atrial fibrillation (AF). While oral anticoagulation with vitamin K antagonists (AVKs) substantially reduces this risk, this requires regular monitoring of the international normalized ratio (INR) in order to achieve therapeutic levels (2,0-3,0). The aim of this study was to evaluate a group at high risk of cerebral infarction, among patients with AF undergoing long-term treatment with VKAs, taking into account the significance of therapeutic INR values. The analysed group consisted of 90 acute ischaemic stroke patients with paroxysmal or chronic “non-valvular” AF, receiving treatment with VKAs. As a result of the study, therapeutic INR values (≥ 2) were seen in thirty-five of these individuals (38,8%), while 55 (61,2%) showed non-therapeutic INR values. Moreover, there were no differences in demographics, vascular risk factors, biochemical and morphological blood parameters, mean CHA2DS2-VASc score and TOAST classification between either of the two groups. Furthermore, no additional factor that would increase their risk of cerebral infarction during the adequate treatment with VKAs was found. However, patients with non-therapeutic INR values had a statistically significantly higher frequency of concomitant moderate pathology of the bicuspid valve, p<0.05. Hence, a lack of proper control of INR can proved to be particularly dangerous for this subgroup of patients. Hence, this is a group with an elevated risk of cerebral infarction and therefore requires special oversight of VKA treatment or NOA treatment.

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P3851Benefit-risk profile of dabigatran compared with vitamin-K antagonists in elderly patients with non-valvular atrial fibrillation: results from a cohort study in the French nationwide claims database

European Heart Journal ◽

10.1093/eurheartj/ehy563.p3851 ◽

2018 ◽

Vol 39 (suppl_1) ◽

Author(s):

Y Cottin ◽

P Blin ◽

J Benichou ◽

C Dureau-Pournin ◽

A Abouelfath ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Elderly Patients ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Risk Profile ◽

Claims Database

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P3472Modifications of renal function in atrial fibrillation patients treated with different oral anticoagulants: a multicentre cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz745.0344 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

D Pastori ◽

G Y H Lip ◽

A Sciacqua ◽

F Perticone ◽

F Melillo ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Cohort Study ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Forest Plot ◽

Multicentre Cohort Study ◽

Egfr Decline ◽

Multicentre Cohort

Abstract Background A decline of estimated glomerular filtration rate (eGFR) has been described in atrial fibrillation (AF) patients on Vitamin K antagonists (VKAs). Few real-world data on the modifications of eGFR in AF patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) do exist. Purpose To evaluate changes of renal function in AF patients treated with VKAs or NOACs. Methods Multicentre prospective cohort study including 1,667 patients with non-valvular AF from 5 clinical centres of Internal Medicine and Cardiology in Italy. Renal endpoints were: 1) median annual decline of eGFR; 2) transition to eGFR <50 ml/min/1.73 m2; 3) eGFR class worsening according to KDIGO 2012 classification. The eGFR was assessed by the CKD-EPI formula at baseline and during follow-up. Results Median age was 73.7±9.1 years and 43.3% were women. 743 patients were on VKAs and 924 on NOACs (Dabigatran, Rivaroxaban e Apixaban). Median annual eGFR decline was −2,11 (Interquartile Range [IQR] −5,68/−0,62] in patients on VKAs, −0,27 [IQR −9,00/4,54] with Dabigatran (p<0.001 vs. VKAs), −1,21 [IQR −9,98/4,02] with Rivaroxaban (p=0.004 vs. VKAs) and −1,32 [IQR −8,7/3,99] with Apixaban (p=0.003, vs. VKAs). Use of Dabigatran and Apixaban was associated to a lower transition to eGFR <50 mL/min/1.73 m2, compared to VKAs: adjusted Odds Ratio (aOR) 0.492, 95% Confidence Interval (CI) 0.298–0.813, p=0.006 for Dabigatran; aOR 0.449, 95% CI 0.276–0.728, p=0.001 for Apixaban). Regarding the eGFR class worsening, Dabigatran (aOR 0.70, 95% CI 0.503–0.975, p=0.035), Rivaroxaban (aOR 0.591, 95% CI 0.423–0.825, p=0.002), and Apixaban (aOR 0.591, 95% CI 0.429–0.815, p=0.001) were all associated to a lower rate of eGFR class worsening compared to VKAs. Forest plot Conclusions In this prospective multicentre cohort study, NOACs use was associated with a lower decline of renal function compared to VKAs. Patients on Dabigatran showed the lowest annual rate of eGFR decline and those on Apixaban and Rivaroxaban a lower eGFR class worsening. Acknowledgement/Funding None

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Long-term quality of VKA treatment and clinical outcome after extreme overanticoagulation in 14,777 AF and VTE patients

Thrombosis and Haemostasis ◽

10.1160/th14-06-0537 ◽

2015 ◽

Vol 113 (04) ◽

pp. 881-890 ◽

Cited By ~ 9

Author(s):

Nic J. G. M. Veeger ◽

Nakisa Khorsand ◽

Hanneke C. Kluin-Nelemans ◽

Hilde A. M. Kooistra ◽

Karina Meijer ◽

...

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Clinical Outcome ◽

Vitamin K ◽

Vitamin K Antagonists ◽

P Value ◽

Risk Of Bleeding ◽

Increased Risk

SummaryVitamin K antagonists (VKA) are widely used in atrial fibrillation and venous thromboembolism (VTE). Their efficacy and safety depend on individual time in the therapeutic range (iTTR). Due to the variable dose-response relationship within patients, also patients with initially stable VKA treatment may develop extreme overanticoagulation (EO). EO is associated with an immediate bleeding risk, but it is unknown whether VKA treatment will subsequently restabilise. We evaluated long-term quality of VKA treatment and clinical outcome after EO. EO was defined as international normalized ratio (INR) ≥ 8.0 and/or unscheduled vitamin K supplementation. We included a consecutive cohort of initially stable atrial fibrillation and venous thromboembolism patients. In EO patients, the 90 days pre- and post-period were compared. In addition, patients with EO were compared with patients without EO using a matched 1:2 cohort. Of 14,777 initially stable patients, 800 patients developed EO. The pre-period was characterised by frequent overanticoagulation, and half of EO patients had an inadequate iTTR (< 65 %). After EO, underanticoagulation became more prevalent. Although the mean time between INR-measurements decreased from 18.6 to 13.2 days, after EO inadequate iTTR became more frequent (62 %), p-value < 0.001. A 2.3 times (95 % confidence interval [CI] 2.0–2.5) higher risk for iTTR< 65 % after EO, was accompanied by increased risk of bleeding (hazard ratio [HR] 2.1;CI 1.4–3.2), VKA-related death 17.0 (HR 17.0;CI 2.1–138) and thrombosis (HR 5.7;CI 1.5–22.2), compared to the 1600 controls. In conclusion, patients continuing VKA after EO have long-lasting inferior quality of VKA treatment despite intensified INR-monitoring, and an increased risk of bleeding, thrombosis and VKA-related death.Note: There have been no previous presentations, reports or publications of the complete data that appear in the article. Parts of the data in this article have been presented as a poster at the American Society of Hematology (ASH) congress 2013, New Orleans, United States.

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