Long-Term Health Benefits of Treating Non-Valvular Atrial Fibrillation with Apixaban Versus Vitamin K Antagonists In Germany: A Population-Based Modelling 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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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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Cancer risk in long-term users of vitamin K antagonists: A population-based case-control study

International Journal of Cancer ◽

10.1002/ijc.27905 ◽

2012 ◽

Vol 132 (11) ◽

pp. 2606-2612 ◽

Cited By ~ 18

Author(s):

Anton Pottegård ◽

Søren Friis ◽

Jesper Hallas

Keyword(s):

Cancer Risk ◽

Vitamin K ◽

Case Control Study ◽

Vitamin K Antagonists ◽

Population Based ◽

Case Control ◽

Control Study

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Methodological considerations for investigating oral anticoagulation persistence in atrial fibrillation

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvaa052 ◽

2020 ◽

Author(s):

Miney Paquette ◽

Lawrence Mbuagbaw ◽

Alfonso Iorio ◽

Robby Nieuwlaat

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Patient Selection ◽

Vitamin K Antagonists ◽

Reliability And Validity ◽

Study Methodology ◽

Methodological Considerations ◽

Study Designs

Abstract Aims Reports of long-term oral anticoagulant (OAC) therapy for atrial fibrillation (AF) reveal highly variable, and generally suboptimal estimates of medication persistence. The objective of this review is to summarize current literature and highlight important methodological considerations for interpreting persistence research and designing studies of persistence on OAC treatment. Methods and results We summarize differences in study methodology, setting, timing, treatment, and other factors associated with reports of better or worse persistence. For example, prospective compared with retrospective study designs are associated with higher reported persistence. Similarly, patient factors such as permanent AF or high stroke risk, and treatment with non-vitamin K oral antagonists relative to vitamin K antagonists are associated with higher persistence. Persistence has also been reported to be higher in Europe compared with North America and higher when the treating physician is a general practitioner compared with a specialist. We propose a framework for assessing and designing persistence studies. This framework includes aspects of patient selection, reliability and validity of measures, persistence definitions, clinical utility of measurements, follow-up periods, and analytic approaches. Conclusions Differences in study design, patient selection, treatments, and factors such as the countries/regions where studies are conducted or the type of treating physician may help explain the variability in OAC persistence estimates. A framework is proposed to assess persistence studies. This may have utility to compare and interpret published studies as well as for planning of future studies.

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Vitamin K antagonists

Hämostaseologie ◽

10.5482/ha-12050008 ◽

2012 ◽

Vol 32 (04) ◽

pp. 249-257 ◽

Cited By ~ 5

Author(s):

T. F. Luscher ◽

J. Steffel

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Drug Interactions ◽

Vitamin K ◽

Stroke Prevention ◽

Vitamin K Antagonists ◽

Term Treatment ◽

Thrombin Inhibitor ◽

Long Term Treatment

SummaryFor the last decades, anticoagulation for stroke prevention in atrial fibrillation (AF) as well as for the prophylaxis and long-term treatment of venous thromboembolism has been entirely based on vitamin K antagonists (VKA). Although very effective under optimal conditions, long-term treatment with these drugs is flawed by the fact that the time in the therapeutic range frequently is suboptimal due to biological factors, drug interactions and compliance.The direct thrombin inhibitor dabigatran, as well as the direct FXa inhibitors rivaroxaban and apixaban provide more consistent anticoagulation and have proven their efficacy and safety against VKAs in several large scale randomized clinical trials for stroke prevention in atrial fibrillation as well as for the treatment and prevention of venous thromboembolism. In view of these convincing data and other advantages such as the lack of mandatory monitoring and only few drug interactions,VKAs will most likely be replaced in a majority of patients for these indications. Based on the most recent trial evidence, the current review discusses the role of VKA treatmentand that of the novel anticoagulants.

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