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Mechanical heart valve prosthesis and warfarin: treatment quality and prognosis
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Internal medicine, Sundsvall Hospital.
Department for Coagulation Disorders, University of Lund, Malmö, Sweden.
Department of Research and Development, County Council of Västernorrland, Sundsvall Hospital, Sundsvall, Sweden.
Department for Coagulation Disorders, University of Lund, Malmö, Sweden.
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2014 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 133, no 5, 795-798 p.Article in journal (Refereed) Published
Abstract [en]

Introduction: Every year about 2500 patients in Sweden undergo surgery due to heart valve disease. A mechanical heart valve prosthesis causes risk of thromboembolic stroke or thrombus formation in the valve while anticoagulant treatment increases the risk of bleeding. Treatment quality with warfarin is crucial for patients with mechanical valve prostheses. It has previously been shown that poorly controlled warfarin treatment increases mortality in this patient group. TTR (Time in Therapeutic Range) on warfarin has been shown to affect the risk of complications in atrial fibrillation, but has not been studied in patients with mechanical heart valves. Our aim is to evaluate the impact of TTR on the risk of complications in this patient group. Materials and Methods: A non-randomized, prospective study of 534 adults with mechanical heart valve prostheses from Malmo and Sundsvall registered in the Swedish National Quality Registry Auricula between 01.01.2008 and 31.12.2011. Quartiles regarding individual TTR levels were compared regarding risk of complications. Results: The risk of complications was significantly higher at lower TTR levels for all complications (p = 0.005), bleeding (p = 0.01) and death (p = 0.018) but not for thromboembolism. In multivariate analysis the risk was significantly increased at lower TTR levels for bleeding and all complications but not for death or thromboembolism. Conclusion: Patients with a lower warfarin treatment quality measured by TTR have a higher risk of complications such as severe bleeding or death. A TTR of 83% or higher at the individual level should be obtained for best outcome.

Place, publisher, year, edition, pages
Elsevier, 2014. Vol. 133, no 5, 795-798 p.
Keyword [en]
TTR, Warfarin, Mechanical heart valve prosthesis
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:umu:diva-89216DOI: 10.1016/j.thromres.2014.02.031ISI: 000334739100017OAI: oai:DiVA.org:umu-89216DiVA: diva2:720106
Available from: 2014-05-28 Created: 2014-05-26 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Anticoagulation treatment in patients with a mechanical heart valve
Open this publication in new window or tab >>Anticoagulation treatment in patients with a mechanical heart valve
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background

Every year about 2,500 patients in Sweden undergo surgery for heart valve disease, primarily in the aortic valve.  In contrast to the mitral valve, which can be repaired in 70% of the cases, the aortic valve is normally replaced by a mechanical or biological prosthesis. A mechanical heart valve (MHV) necessitates lifelong anticoagulation treatment with a vitamin K antagonist, most commonly warfarin, due to the high thrombogenicity of the prosthesis. The quality of the warfarin treatment is crucial in these patients. Compared to other countries, treatment quality in Sweden is very high; nonetheless, there is always room for improvement. One of the ways to achieve this improvement is to implement computerized dosing assistance. Treatment recommendations for anticoagulation intensity are based on few and old studies, making these recommendations uncertain. There is therefore a need for studies designed to establish the appropriate level of anticoagulation therapy.

Aim

The aim of these studies was to investigate the efficacy and safety of anticoagulation treatment among patients with mechanical heart valve prostheses in Sweden; to assess whether computerized dosing can increase the treatment quality; to investigate the influence of the treatment quality, measured by Time in Therapeutic Range (TTR) and INR variability, on the risk of complications and, finally, to establish the optimal intensity of anticoagulation treatment in this group of patients.

Methods

Data were obtained from AuriculA – a national quality registry established in 2006, which currently includes approximately 50% of all patients treated with oral anticoagulation in Sweden.

Study II used only data from AuriculA. 769,933 warfarin-dosing suggestions proposed by the dosing algorithm in AuriculA were analysed. Accepted dose suggestions (590,939) were compared with 178,994 manually-changed doses in regard to the resultant INR value, measured as mean error (deviation from target INR) and hit rate (number of INR samples within the target range 2-3).

In study III, AuriculA was used to identify patients in Sundsvall and Malmö in the period 2008 – 2011 who were receiving warfarin for a mechanical heart valve prosthesis, as well as to retrieve their INR data. Data on background characteristics and bleedings or thromboembolic complications were manually retrieved from medical records by two investigators.  A total of 534 patients with mechanical heart valve prostheses were divided into quartiles based on TTR and were compared regarding the risk of complications.

For Studies I and IV, data from AuriculA were merged with the Swedish National Patient Register, SWEDEHEART/ Heart surgery, and the Swedish Cause of Death Register, comprising in total 77,423 patients on warfarin with 217,804 treatment years. Every treatment period registered in AuriculA was given an individual identification number. During the study period a patient could have any number of treatment periods. The number of complications in total and in different patient groups within the study population was investigated. Complications were defined by ICD-10 codes. Major bleeding was defined as an event necessitating hospital treatment and given a discharge diagnosis with one of the ICD-10 codes reflecting bleeding, as listed in the Appendix. Bleeding events were divided into intracranial, gastrointestinal and other bleedings. Thromboembolic complications consist of venous events (deep vein thrombosis, pulmonary embolism, venous stroke) or arterial events (stroke, TIA, acute myocardial infarction, peripheral arterial embolism).

Data were analysed using both simple, descriptive statistical methods and various tests such as Mann-Whitney (or two sample Wilcoxon), T-test, Chi 2 test, ANOVA, multivariate analysis with logistic regression and survival analysis with Cox Regression with proportional hazard assumption.

Results

Treatment quality 

Mean TTR among all patients in Study I was 76.5% whereas patients with mechanical heart valve prostheses had a TTR of 74.5%. The annual incidence of major bleeding or thromboembolic events among all patients was 2.24% and 2.65%, respectively. The incidence of intracranial bleeding was 0.37% per year in the general population and 0.51% among patients with mechanical heart valve prostheses, who also had a higher bleeding rate in total (3.37% per year).

Both the mean and median errors were smaller (0.44 vs. 0.48 and 0.3 vs. 0.4, respectively) and the hit rate was higher (0.72 vs. 0.67) when the dose suggested by the algorithm was accepted, compared to when it was manually changed.

TTR 

In Study III there was no significant difference in the risk of thromboembolism regardless of TTR level. Risk of bleeding in quartiles I and II was more than two times higher than in the quartile with TTR >82.9.

In Study IV, lower TTR (≤70%) was associated with a significantly higher rate of complications when compared with TTR >70%. Bleeding risk was higher in the group with lower TTR (HR=2.43, CI 2.02-2.89, p<0.001). After dividing patients into TTR quartiles, the rate of complications in total was significantly higher in quartiles I to III compared with quartile IV, which had the highest TTR. Risk of thromboembolism, major bleeding and death was higher in the first and second quartile compared to the quartile with the highest TTR.

INR variability 

Higher INR variability above mean (≥0.40) was related to a higher rate of complications compared with lower INR variability (<0.40) as shown in Study IV. Bleeding risk was higher in the group with INR variability ≥0.40 (HR = 2.15, CI 1.75-2.61, p<0.001).

Comparison of quartile IV, which had the lowest INR variability, with the other three revealed that quartiles I and II, which had the highest INR variability, had significantly worse outcomes for all complications except for thromboembolic events, plus also death in quartile II.

TTR and INR variability combined 

High variability and low TTR combined was associated with a higher risk of bleedings (HR 2.50, CI 1.99-3.15), death (3.34, CI 2.62-4-27) and thrombosis (1.55, CI 1.21-1.99) compared to the best group.

Level of anticoagulation

Higher warfarin treatment intensity (mean INR 2.8-3.2 vs. 2.2-2.7) was associated with a higher rate of bleedings (HR 1.29, CI 1.06-1.58), death (1.73, CI 1.38-2.16) and complications in total (1.24, CI 1.06-1.41) after adjustment for MHV position, age and comorbidity.

Conclusion

Warfarin treatment quality is crucial for patients with mechanical heart valve prostheses. Computerized dosing assistance could help maintain high warfarin treatment quality.

Well-managed treatment with TTR ≥70% and INR variability below mean <0.40 is associated with a lower risk of serious complications compared with a lower TTR and higher INR variability.

No benefit of higher warfarin treatment intensity was found for any valve type or position.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2016. 72 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1831
Keyword
Mechanical heart valve, anticoagulation, warfarin, Time in Therapeutic Range (TTR), INR variability
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-128355 (URN)978-91-7601-539-1 (ISBN)
Public defence
2017-01-13, Aulan, Sundsvalls sjukhus, Lasarettsvägen, Sundsvall, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-12-21 Created: 2016-12-02 Last updated: 2016-12-21Bibliographically approved

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