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Bleeding complications and mortality in warfarin-treated VTE patients, dependence of INR variability and iTTR
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. (Sundsvall Research Unit, Umeå University)
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. (Sundsvall Research Unit, Umeå University)
2017 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 117, no 1, 27-32 p.Article in journal (Refereed) Published
Abstract [en]

High quality of warfarin treatment is important to prevent recurrence of venous thromboembolism (VTE) without bleeding complications. The aim of this study was to examine the effect of individual time in therapeutic range (iTTR) and International Normalised Ratio (INR) variability on bleeding risk and mortality in a large cohort of well-managed patients with warfarin due to VTE. A cohort of 16612 patients corresponding to 19502 treatment periods with warfarin due to VTE between January 1, 2006 and December 31, 2011 was retrieved from the Swedish national quality register AuriculA and matched with the Swedish National Patient Register for bleeding complications and background characteristics and the Cause of death register for occurrence and date of death. The rate of bleeding was 1.79 (confidence interval (CI) 95 % 1.66-1.93) per 100 treatment years among all patients. Those with poor warfarin treatment quality had a higher rate of clinically relevant bleeding, both when measured as iTTR below 70 %, 2.91 (CI 95 % 2.61-3.21) or as INR variability over the mean value 0.85, 2.61 (CI 95 % 2.36-2.86). Among those with both high INR variability and low iTTR the risk of clinically relevant bleeding was clearly increased hazard ratio (HR) 3.47 (CI 95 % 2.89-4.17). A similar result was found for all-cause mortality with a HR of 3.67 (CI 95 % 3.02-4.47). Both a low iTTR and a high INR variability increase the risk of bleeding complications or mortality. When combining the two treatment quality indicators patients at particular high risk of bleeding or death can be identified.

Place, publisher, year, edition, pages
2017. Vol. 117, no 1, 27-32 p.
Keyword [en]
TTR, INR variability, venous thromboembolism, bleeding, warfarin, all-cause mortality
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:umu:diva-127526DOI: 10.1160/TH16-06-0489ISI: 000391350600006PubMedID: 27652593OAI: oai:DiVA.org:umu-127526DiVA: diva2:1046716
Available from: 2016-11-15 Created: 2016-11-15 Last updated: 2017-04-17Bibliographically approved
In thesis
1. Efficacy and safety of warfarin treatment in venous thromboembolic disease
Open this publication in new window or tab >>Efficacy and safety of warfarin treatment in venous thromboembolic disease
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background

As a major cause of morbidity and mortality treatment of venous thromboembolism is important, with the correct use of anticoagulants it is possible to greatly reduce both mortality and morbidity. Warfarin is among the most widely used anticoagulants being effective in treatment and prevention of venous thromboembolism with few negative side effects other than bleeding complications. With a narrow therapeutic window warfarin treatment requires constant monitoring and adjustments to stay effective without an increased bleeding risk.

The aim of this thesis was to study the efficacy and safety of warfarin treatment in venous thromboembolic disease.

Methods

Using AuriculA, the Swedish national quality register for atrial fibrillation and anticoagulation, a cohort was created of patients registered with warfarin treatment during the study time January 1st 2006 to December 31th 2011, including all different indications for anticoagulation. In all four studies the study design was retrospective with information added to the cohort from the Swedish national patient register about background data and endpoints in form of bleeding complications in all studies and thromboembolic events in study 1 and 2. In study 3 and 4 information was added from the cause of death register about occurrence of death and in study 3 cause of death. In study 3, information from the prescribed drugs register about retrieved prescriptions of acetylsalicylic acid was added.

Results

In study 1 the mean TTR was found to be high both among patients managed at primary healthcare centres and specialised anticoagulation clinics at 79.6% and 75.7%. There was no significant difference in rate of bleeding between the two types of managing centres being 2.22 and 2.26 per 100 treatment years. In study 2 no reduction in complication rate with increasing centre TTR was seen for patients with atrial fibrillation with few centres having centre TTR below 70% (2.9%), in contrast to previous findings by Wan et al(1). For those with warfarin due to VTE where a larger proportion of the centres had centre TTR below 70% (9.1%) there was a reduction in complication rate with increasing centre TTR. Among the 13859 patients with treatment for VTE in study 3 age (HR 1.02, CI 95% 1.01-1.03), hypertension (HR 1.29, CI 95%1.02-1.64), Cardiac failure (HR 1.55, CI 95% 1.13-2.11), chronic obstructive pulmonary disease (HR 1.43, CI 95% 1.04- 1.96), alcohol abuse (HR 3.35, CI 95% 1.97-5.71), anaemia (HR 1.77, CI 95% 1.29-2.44) and a history of major bleeding (HR 1.75, CI 95% 1.27-2.42) increased the risk of bleeding during warfarin treatment. In study 4 both those with high iTTR and those with low INR variability had a low rate of bleedings at 1.27 (1.14-1.41) or 1.20 (0.94-1.21) per 100 treatment years compared to those with low iTTR and high INR variability having a rate of bleeding at 2.91 (2.61-3.21) or 2.61 (2.36-2.86) respectively. Those with the combination of both low iTTR and high INR variability had an increased risk of bleeding, hazard ratio HR 3.47 (CI 95 % 2.89-4.17). The quartile with both the lowest iTTR and the highest INR variability had an increased risk of bleeding with a hazard ratio 4.03 (3.20-5.08) and 3.80 (CI 95%, 3.01-4.79) compared to the quartile with the highest iTTR and lowest INR variability.

Conclusion

It is possible to achieve a safe warfarin treatment both in specialised anticoagulation centres and in primary health care. At initiation of treatment some of the patients at high risk of bleeding can be identified using knowledge about their background. With the use of quality indicators as TTR and INR variability during treatment those at high risk of complications can be identified and analysing treatment quality on centre level gives an opportunity to identify improvement areas among managing centres. With the addition of new treatment options warfarin can still be the most suitable option for some patients, being safe and effective when well managed.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2017. 61 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1895
Keyword
Warfarin, Venous thromboembolism, Bleeding
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-133618 (URN)978-91-7601-701-2 (ISBN)
Public defence
2017-05-12, E04_R1, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2017-04-21 Created: 2017-04-17 Last updated: 2017-05-05Bibliographically approved

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