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Bleeding complications in venous thrombosis patients on well-managed warfarin
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)
2016 (English)In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 41, no 2, 351-358 p.Article in journal (Refereed) Published
Resource type
Text
Abstract [en]

Anticoagulation treatment is effective in preventing both death and recurrence in patients with venous thromboembolism (VTE), but at the same time confers a substantial risk of bleeding complications. The aim of this study was to examine the rate of and predictors for bleeding complications in VTE patients on warfarin with high treatment quality. In total 13,859 patients on warfarin for VTE between January 1st 2006 and December 31th 2011 were retrieved from the national quality register Auricula. The cohort was matched with the Swedish National Patient Register for complications and background characteristics, the Cause of Death Register for date and cause of death and the Swedish Prescribed Drug Register for retrieved medication. The rate of major bleeding was 2.36 per 100 treatment years, increasing with age from 1.25 to 4.33 for those under 60 or over 80 years of age, respectively. Factors found to independently increase the risk of bleeding complications were increasing age HR 1.02, cardiac failure HR 1.39, Chronic pulmonary disease HR 1.41, alcohol abuse HR 3.33, anaemia HR 1.75, hypertension HR 1.29 and a history of major bleeding HR 1.69. Warfarin as treatment for VTE is safe with a low rate of bleeding complications at least for the younger patient. In an era of NOAK, warfarin has a comparable safety profile among VTE patients and is still a valid treatment option.

Place, publisher, year, edition, pages
2016. Vol. 41, no 2, 351-358 p.
Keyword [en]
Venous thromboembolism, Bleeding, Warfarin, TTR
National Category
Hematology Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:umu:diva-117396DOI: 10.1007/s11239-015-1305-4ISI: 000369338900016PubMedID: 26660340OAI: oai:DiVA.org:umu-117396DiVA: diva2:916951
Note

Special Issue: Measurement Tools and Antidotes for Non-Vitamin K Oral Anticoagulants

Available from: 2016-04-05 Created: 2016-02-29 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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