• Routine use of anticoagulation after transcatheter aortic valve replacement: Initial safety outcomes from a single-center experience

    Abstract

    Background

    Subclinical leaflet thrombosis (SCLT) can be seen in up to 12% of patients after transcatheter aortic valve replacement (TAVR). Anticoagulation appears to prevent and reverse SCLT but concerns exist about bleeding risk.

    Methods

    Our program adopted a strategy of routine anticoagulation after TAVR, starting warfarin on post-procedure day 0 and continuing for 3 months in 10/2015. We report the initial safety and efficacy outcomes of this approach. Bleeding events were assessed using Valve Academic Research Consortium (VARC) and Bleeding Academic Research Consortium (BARC) definitions.

    Results

    The median (IQR) age of the population ( = 191) was 82 years (72–87) and the median (IQR) STS score was 5.6% (3–8). A total of 101 (53%) patients were discharged on anticoagulation (warfarin 97%) while 90 (47%) received antiplatelet therapy alone. The mean duration of anticoagulation therapy was 81 ± 17 days. During follow-up 7 patients (4%) had a stroke or TIA, 3 (3%) in the anticoagulation group and 4 (4%) in the antiplatelet group ( = 0.71). A total of 8 patients (4.2%) had BARC bleeding events during follow-up, 3 patients in the anticoagulation group (2.9%) and 5 in the antiplatelet group (5.5%, = 0.48). All bleeding events (VARC and BARC) were numerically lower in the anticoagulation group (8% versus 13%, = 0.20).

    Conclusions

    A strategy of routine anticoagulation for 3-months after TAVR is well tolerated and associated with similar or lower bleeding risk compared to antiplatelet therapy.

    Introduction

    In 2015 Makkar et al. reported the first case series of reduced aortic-valve leaflet motion among patients undergoing surgical and transcatheter aortic valve replacement (TAVR) in a clinical trial and two registries  . Among patients receiving antiplatelet therapy the incidence of reduced leaflet motion was 55% in the clinical trial and 29% in the pooled registries  . In contrast, among patients treated with warfarin the incidence of reduced leaflet motion was 0%. Of the 11 patients with reduced leaflet motion that underwent follow-up computed tomography (CT), and were prescribed warfarin, restoration of leaflet motion was noted in all. Although the clinical significance of this imaging finding remains under investigation, the prevailing view is that it represents subclinical leaflet thrombosis (SCLT) of bioprosthetic aortic valves  . In a follow-up study Chakravarty et al. showed that SCLT is associated with increased trans-valvular gradients, increased risk of stroke and transient ischemic attack (TIA)  .

    The risk of thromboembolism after surgical aortic valve replacement (SAVR) is highest in the first 90 days after the operation (up to 41% in the first 10 days) and then decreases to 1.9%/year beyond 90 days  . Given these considerations our heart team decided to change the antithrombotic regimen after TAVR in October 2015; from dual antiplatelet therapy with clopidogrel and aspirin (ASA) to warfarin therapy to a goal international normalized ratio (INR) between 2 and 3 for 90 days and life-long ASA, unless contraindications to anticoagulation were present. In this manuscript we report our early experience with this approach.

    Methods

    Setting

    The Minneapolis VA Healthcare System (MVAHCS) is a tertiary, 250-bed hospital within the VA Midwest Heath Care Network (Veterans Integrated Service Network VISN 23). The network serves > 440,000 enrolled Veterans residing in the states of Iowa, Minnesota, Nebraska, North Dakota, South Dakota, and portions of Illinois, Kansas, Missouri and Wyoming. The MVAHCS is the only approved TAVR program in a nine state area and has an academic affiliation with the University of Minnesota Medical Center (UMMC)  . The TAVR program at the Minneapolis VAMC was established in April of 2015. Prior to that date, all of TAVR procedures were performed at the University of Minnesota Medical Center.

    Patients, study intervention and outcomes

    We included 191 patients treated with TAVR at MVAHCS and the University of Minnesota Medical Center (UMMC) from April 2015 to February 2017. We excluded patients that underwent transcatheter valve replacement in a non-aortic position (i.e. mitral valve in valve procedures or pulmonary). Patients that underwent TAVR procedures for off label indications (bicuspid valve, aortic insufficiency) and/or valve-in-valve (VIV) procedures were included in the analysis.

    Prior to October 2015 ( Period 0 or pre-intervention ) our antithrombotic regimen consisted of dual antiplatelet therapy with clopidogrel 75 mg daily for 6 months and life-long ASA 81 mg daily. After October 2015 ( Period 1 or post-intervention ) the antithrombotic regimen consisted of warfarin (without bridging) starting on postoperative day 0 and continuing for 90 days or longer (if indicated for other reasons such as deep venous thrombosis, pulmonary embolism, or atrial fibrillation) in conjunction with life-long ASA 81 mg daily. The decision to use low-dose aspirin is consistent with current ACC/AHA guidelines. Patients with contraindications to anticoagulation were discharged on antiplatelet therapy and were included in the control group. Patients treated at UMMC in 2015 were included in the control group since this program never adopted the anticoagulation regimen. Therefore, the control group was comprised of patients treated at the MVAHCS pre- intervention as well as post-intervention as long as they had relative or absolute contraindications to anticoagulation, and patients treated at our University affiliate in 2015 (Supplementary Appendix Table 3). We compared the outcomes of patients discharged on anticoagulation versus antiplatelet therapy.

    Outcomes measures included stroke, transient ischemic attack (TIA), vascular complications, bleeding, and in-hospital mortality. Outcomes were prospectively defined according to the Valve Academic Research Consortium (VARC) definitions  . Rates of bleeding 90-days after the index TAVR procedure were assessed using Bleeding Academic Research Consortium (BARC) definitions  . All patients treated with anticoagulation were enrolled in a dedicated anticoagulation clinic staffed by trained pharmacist and hematologists. All patients underwent echocardiograms for assessment of trans-valvular gradients and routine clinic visits between 30 and 90 days post procedure.

    Statistical methods

    Continuous variables are presented as mean ± SD, or as median with interquartile range when appropriate. Categorical variables are reported as frequencies and percentages. Continuous variables were compared using the unpaired Student t- test or Mann-Whitney test as appropriate. Discrete variables were compared with the chi-square test or Fisher exact test as appropriate. A 2-sided value < 0.05 was considered to be statistically significant. Medcalc® version 17.2 was used for analysis.

    This study was approved by the Institutional Review Board of the Minneapolis VA Medical Center and University of Minnesota. Individual consent requirement was waived.

    Results

    The study population consisted 191 consecutive patients undergoing TAVR between 2015 and 2017. The median (interquartile range) age of the patients was 82 years (72–87) and the median (IQR) Society of Thoracic Surgeons (STS) risk score was 5.6 (3–8). Baseline characteristics are presented in Table 1 . A total of 101 patients (53%) were discharged on anticoagulation and 90 (47%) on antiplatelet therapy alone. Of the 101 patients treated with anticoagulation, 97 received warfarin and 3 received a novel oral anticoagulant (NOAC) for a mean (± SD) duration of 81 days (17). In addition, 76 (84%) received antiplatelet therapy with ASA or clopidogrel. Of the patients discharged on antiplatelet therapy alone 83 (92%) received ASA and 76 (84%) received dual antiplatelet therapy (DAPT) for 6 months ( Table 2 ). Thirteen patients underwent TAVR after the intervention but were discharged on antiplatelet therapy alone because of real or perceived contraindications to anticoagulation. A summary of contraindications to anticoagulation, as listed in the medical record, is presented in Table 1 of the Supplemental Appendix. The median time to therapeutic INR in the anticoagulation group was 11 days (IQR: 16 days). The proportion of therapeutic INRs (between 2.0 and 3.0) relative to the total number of INRs measured was 43% (± 19) among patients followed the VA. Atrial fibrillation was more prevalent in the anticoagulation group (44% versus 17%, < 0.01). The mean (± SD) HASBLED score was 2.9 (0.7) in the control group and 3.5 (1.2) in the anticoagulation group ( < 0.01). Otherwise there were no significant inter-group differences ( Table 1). 

    Table 1
    Baseline characteristics.
    ParameterOverall ( = 191)Control ( = 90)AC ( = 101)P
    Age–years median- IQR 82 (72–87) 82 (73–87) 81 (72–87) 0.90
    Male gender 83% 72% (65) 92% (93) 1.00
    STS score median- IQR 5.6 (3–8) 6.7 (3–9) 5 (3–7) 0.16
    Weight (kg) 90 ± 23 85 ± 25 94 ± 20 < 0.01
    COPD 40% (76) 38% (34) 42% (42) 0.18
    Dialysis 6% (11) 3% (3) 8% (8) 0.13
    Prior PCI 30% (57) 42% (38) 19% (19) < 0.01
    Prior CABG 27% (52) 23% (21) 31% (31) 0.27
    Prior AF 31% (59) 17% (15) 44% (44) < 0.01
    Home O2 13% (25) 12% (11) 14% (14) 0.60
    TIA 12% (22) 9% (8) 14% (14) 0.21
    Prior CVA 15% (29) 9% (8) 21% (21) 0.01
    Prior myocardial infarction 19% (36) 30% (27) 9% (9) < 0.01
    Prior heart failure 29% (56) 36% (32) 24% (24) 0.20
    EF- % mean ± SD 51 ± 11 52 ± 12 50 ± 11 0.25
    Immunocompromised 11% (21) 12% (11) 10% (10) 0.74
    BMI 31 ± 7 30 ± 8 32 ± 6 0.06
    Creatinine median- IQR 1.1 (0.9–1.4) 1 (0.8–1.4) 1.1 (0.9–1.4) 0.13
    Hemoglobin (g/dl) median- IQR 13 (11–14) 12 (11–14) 13 (11–14) 0.02
    Platelets 196 ± 79 202 ± 90 191 ± 64 0.35
    Albumin 3.5 ± 0.5 3.5 ± 0.4 3.4 ± 0.5 0.53
    HASBLED score, mean (± SD) 3.2 ± 1 2.9 ± 0.7 3.5 ± 1.2 < 0.01
    Table 2
    Procedural characteristics and in-hospital outcomes.
     Overall ( = 191)Control ( = 90)AC ( = 101)P
    Procedural characteristics        
    Transfemoral access 81% (155) 73% (66) 88% (89) 0.01
    Alternative access 19% (36) 27% (24) 12% (12) 0.01
    Balloon-expandable 80% (153) 78% (70) 82% (83) 0.45
    Self-expandable 20% (38) 22% (20) 18% (18) 0.45
    Valve-in-valve 8% (15) 10% (9) 7% (7) 0.49
    Valve size (mm)       0.06
    23 mm 18% (34) 23% (21) 13% (13)  
    26 mm 37% (70) 38% (34) 36% (36)  
    29 mm 39% (75) 32% (29) 46% (46)  
    31 mm 5% (9) 7% (6) 3% (3)  
    34 mm 2% (3) 0% (0) 3% (3)  
    Fluoroscopy time (minutes) Median- IQR 21 (16–30) 20 (13–30) 21 (15–30) 0.23
    Contrast (ml) Median- IQR 115 (75–160) 105 (75–143) 117 (75–180) 0.23
    Length of stay (days) Median- IQR 3 (2–6) 4 (2–6) 3 (2–5) 0.02
    MAC anesthesia (%) 28% (52) 12% (11) 44% (41) < 0.01
    Device success 95% (172) 96% (86) 95% (86) 1.00
    In-hospital outcomes        
    Stroke 0% (0) 0% (0) 0% (0) N/A
    Vascular complications 3% (5) 4% (4) 1% (1) 0.37
    In-hospital bleeding 6% (12) 8% (7) 5% (5) 0.55
    Paravalvular leak (> mild) 1% (2) 1% (1) 1% (1) 1.00
    Pacemaker placement 16% (29) 11% (10) 21% (19) 0.06
    Discharge aortic mean gradient (mmHg) 10 ± 5 10 ± 5 11 ± 5 0.56
    Antithrombotic regimen        
    Aspirin 79% (151) 92% (83) 67% (68) < 0.01
    P2Y12 45% (84) 84% (76) 8% (8) < 0.01
    DAPT 42% (80) 84% (76) 4% (4) < 0.01
    Warfarin 51% (97) 0% 96% (97) < 0.01
    NOAC 2% (3) 0% 3% (3) 0.57

     

    Transfemoral (TF) access was used in 155 patients (81%) and alternative access in 36 (19%). Alternative access included transapical 7.3%, transaortic 0.5%, transilliac 1%, axillary 4%, and subclavian 6%. A balloon-expandable valve (SAPIEN XT or SAPIEN 3, Edwards Life sciences, Irvine, CA) was used in 153 (80%) patients and a self-expandable valve (Corevalve or Evolut R, Medtronic, Minneapolis, MN) in the remaining 38 patients (20%). No inter-group differences in access or valve type were seen according to antithrombotic regimen ( Table 2 ). Similarly, median (IQR) fluoroscopy time (21 min, IQR: 15–30 versus 20 min, IQR: 13–30, = 0.23) was not statistically different and length of stay was 3 days (IQR: 2–5) versus 4 days (IQR: 2–6, = 0.02).

    Safety outcomes

    In-hospital

    Eleven (5.7%) episodes of VARC minor bleeding occurred during the index hospital stay, 4 in the anticoagulation group (3.9%) and 7 in the antiplatelet group (7%, = 0.35) ( Fig. 1 and Table 2 Supplemental Appendix). One episode of VARC life-threatening intracranial bleeding occurred in the AC group on post-operative day 1 after a mechanical fall before the INR was therapeutic (INR 1.3). Overall VARC bleeding events (7 or 3.6%) were no different in the two groups (5 versus 7, = 0.55). The mean (± SD) gradient at the time of discharge was 11 mmHg (± 5) in both groups. Other in-hospital events are listed in Table 2 and Supplementary Appendix. 

    Fig. 1
    Use of anticoagulation before and after the implementation of the new antithrombotic regimen. Despite increased use of anticoagulation bleeding and ischemic events remained unchanged.

     

    90-days outcomes

    During follow-up 7 patients (4%) had a stroke or TIA, three (3%) in the anticoagulation group and four (4%) in the antiplatelet group ( = 0.71) ( Table 3 ). A total of 8 patients (7.4%) had BARC bleeding events during follow-up, 3 patients in the anticoagulation group (4%) and 5 patients in the antiplatelet group (5.5%, = 0.48) (Supplementary Appendix Table 2 and Fig. 2 ). All bleeding events (VARC and BARC) were similar between the anticoagulation and control groups (8% versus 13%, = 0.20) ( Table 3 and Figs. 2 and 3 ). The composite of TIA/stroke and any bleeding was numerically lower in the anticoagulation group (11% versus 16%, = 0.10). Overall mortality was low at 30 days (3%) without inter-group differences (4% versus 1%, = 0.20) ( Table 3 ). The mean (± SD) gradient at 90-days was 11 (8) mmHg for the anticoagulation group and 11 (5) mmHg for the antiplatelet group ( = 0.73). The change in mean gradient from baseline to 90-days was also no different between the anti-platelet and anticoagulation groups, respectively (5.7 ± 4.3 versus 4.3 ± 6.6, = 0.12) ( Table 3 ).

    Table 3
    Outcomes at 90 days.
     Overall ( = 191)Control ( = 90)AC ( = 101)P
    Bleeding events (VARC and BARC) 10% (20) 13% (12) 8% (8) 0.20
    Mean gradient at 3-month follow-up (mmHg) 11 ± 7 11 ± 5 11 ± 8 0.73
    Change in mean gradient at 3-month follow-up (mmHg) 4.9 ± 5.7 5.7 ± 4.3 4.3 ± 6.6 0.12
    Ischemic stroke 3% (6) 4% (3) 3% (3) 1.00
    Hemorrhagic stroke 0% (0) 0% (0) 1% (1) 1.00
    Transient ischemic attack (TIA) 0.5% (1) 1% (1) 0% (0) 0.47
    Stroke or TIA 3.1% (6) 4% (3) 3% (3) 0.71
    30-day mortality 3% (5) 4% (4) 1% (1) 0.20
    Fig. 2
    In-hospital bleeding events according to Valve Academic Research Consortium (VARC) definitions.
    Fig. 3
    Bleeding events from hospital discharge up to 90-days according to Bleeding Academic Research Consortium (BARC) definitions.

     

    Discussion

    In this observational study of antithrombotic therapies after TAVR we found that a strategy of routine anticoagulation is feasible in the majority of patients (88%), and associated with similar risk of bleeding and cerebral ischemic events relative to antiplatelet therapy alone.

    The optimal antithrombotic therapy after TAVR remains controversial and a subject of intense investigation  . Dual antiplatelet therapy has been used in the pivotal trials that led the Food and Drug Administration (FDA) to approve transcatheter valves for clinical use  and subsequently adopted as the “default” strategy in clinical practice given absence of randomized clinical trial data. The concerns raised by Makkar et al. regarding the presence of subclinical leaflet thrombosis on surgical and transcatheter bioprosthetic aortic valves prompted a reexamination of what constitutes optimal antithrombotic regimen after TAVR  . A recently published trial comparing single versus double antiplatelet therapy after TAVR (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation or ARTE) showed that single therapy reduces the incidence of major or life-threatening bleeding without increasing the risk of ischemic events  .

    An ideal antithrombotic strategy should reduce clinically relevant end-points during the period in which these events are more likely to occur while having an acceptable side-effect (bleeding) profile. Heras et al. found that the risk of thromboembolism after surgical bioprosthetic valve implantation decreases significantly at each time interval after the operation (day 1–10: 41%/year, day 11–90: 3.6%/year, and > 90 days 1.9%/year, < 0.01) . The same authors found that the risk of thromboembolism was higher among patients who were not taking anticoagulants  . Data from the Danish National Patient Registry confirmed the first 3–6 months after surgery as the period where thromboembolic events are more likely to occur  . Similarly, patients treated with warfarin for 6 months in this large registry had reduced thromboembolic events and cardiovascular death  . Based on these two observational studies, the 2017 American Heart Association (AHA)/American College of Cardiology (ACC) focused update of the guideline for the management of patients with valvular heart disease gave anticoagulation with a vitamin K antagonist (VKA) for at least 3 months, and perhaps 6 months, a Class IIa (reasonable) recommendation after SAVR and a class IIb recommendation after TAVR  . Our study results support this new recommendation. Although long-term anticoagulation can increase the risk of bleeding in the elderly  we found that a brief treatment, which targets the period in which thromboembolic events are more likely to occur, was well tolerated. The bleeding profile of the anticoagulation regimen used in our study was similar to antiplatelet therapy.

    The proportion of therapeutic INRs (between 2.0 and 3.0) relative to the total number of INRs measured was 43% (± 19). In the US Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) 59% of measured INR values were between 2.0 and 3.0  . Patients with renal dysfunction, heart failure, frailty, prior valve surgery, and higher bleeding risk had significantly lower time in therapeutic range (TTR: 0–53%) . Of note, many of these adverse characteristics are highly prevalent among TAVR patients, which may explain the lower TTR relative to AF patients. A previous VA study conducted in 100 VA clinics found a mean TTR of 58% among patients with AF  . The following should be considered when comparing our data with historical AF cohorts: 1) there is an abundance of long-term efficacy data on the use of anticoagulation among AF patients that could have resulted in a more aggressive approach in AF patients, 2) the ideal target INR for patients post-TAVR is not known, 3) patients with no INRs measured in 60 days have been excluded from AF studies, which might have biased the results  . Finally, our results suggest that NOACs may be better suited to achieve the goal of rapid (within 1–2 days post TAVR) and brief (3-month duration) anticoagulation that is highly reproducible across the spectrum of TAVR patients without the need for frequent monitoring.

    Several studies are being conducted to test the optimal antithrombotic strategy after TAVR: 1) Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation ( POPular-TAVI NCT02247128 ) plans to enroll 1000 patients and randomize them into one of four treatment arms (ASA monotherapy, DAPT, oral anticoagulation, or oral anticoagulation plus clopidogrel). The primary end point of POPular-TAVI is freedom from bleeding complication at 1 year, 2) Global Study Comparing a rivaroxaban-based Antithrombotic Strategy to an antiplatelet-based Strategy After Transcatheter aortic valve replacement to Optimize Clinical Outcomes(GALILEO, NCT02556203 ). GALILEO plans to enroll 1500 patients and randomize them to anticoagulation with rivaroxaban plus ASA versus DAPT. The primary end point of GALILEO is a composite of death or first thromboembolic event. A subgroup of 300 patients will be enrolled in the Comparison of a Rivaroxaban-based Strategy With an Antiplatelet-based Strategy Following Successful TAVR for the Prevention of Leaflet Thickening and Reduced Leaflet Motion as Evaluated by Four-dimensional, Volume-rendered Computed Tomography (4DCT) ( GALILEO-4D ). The primary outcome of this sub-study is the proportion of patients with reduce leaflet motion. Until we have definitive answers from randomized clinical trials we think is reasonable to follow ACC/AHA recommendations  .

    Limitations

    Our study has important limitations. First, this is a two-center, observational study in which antithrombotic therapy was not randomly assigned and the investigators and patients were not blinded. Additionally, 44% of the patients in the anticoagulation group were already on anticoagulation prior to receiving a valve for other indications such as atrial fibrillation. As a result, selection bias might have played a role. Second, the sample size is small to adequately address the relative benefits and risks of anticoagulation. Third, the fact that patients were followed at anticoagulation clinics may limit the generalizability of our study results to centers with such clinics. Our findings require validation in larger cohorts. Until then, our study results should be considered hypothesis-generating rather than confirmatory. Finally, our study did not include routine CT imaging during follow-up. We are unable to report on cumulative incidence of subclinical leaflet thrombosis.

    Conclusions

    We found that routine use of anticoagulation for 3-months after TAVR was associated with similar or lower risk of thrombotic and bleeding events.

    Disclosures: Dr. Santiago Garcia has received research support from Edwards Lifesciences and consultant honoraria from Surmodics, Medtronic, and Boston Scientific. Dr. Garcia is a recipient of a career development award ( 1IK2CX000699–01 ) from the VA Office of Research and Development . Dr. Yannopoulos is the PI and co-PI for the following NIH (NHLBI) grants: R01 HL123227 , 1R01HL126092 -01 , R01HL1223231 , R43HL123194-01 1R43HL110517-01A1 , R43HL115937-01 . Dr Yannopoulos also received funds for the Minnesota Resuscitation Consortium from the Medtronic Foundation . The other authors have no conflicts to report related to this manuscript.

    Declaration: All authors listed meet the authorship criteria according to the latest guidelines of the International Committee of Medical Journal Editors, and are in agreement with the manuscript.

    Author bio

    Cardiovascular Revascularization Medicine, 2018-07-01, Volume 19, Issue 5, Pages 621-625, Copyright © 2017

    Source:

    1. [1]Makkar R.R., Fontana G., Jilaihawi H., Chakravarty T., Kofoed K.F., de Backer O., et al: Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. N Engl J Med 2015; 373: pp. 2015-2024
    2. [2]Holmes D.R., and Mack M.J.: Uncertainty and possible subclinical valve leaflet thrombosis. N Engl J Med 2015; 373: pp. 2080-2082
    3. [3]Chakravarty T., Sondergaard L., Friedman J., De Backer O., Berman D., Kofoed K.F., et al: Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. Lancet 2017; 389: pp. 2383-2392
    4. [4]Heras M., Chesebro J.H., Fuster V., Penny W.J., Grill D.E., Bailey K.R., et al: High risk of thromboemboli early after bioprosthetic cardiac valve replacement. J Am Coll Cardiol 1995; 25: pp. 1111-1119
    5. [5]Gurevich S., John R., Kelly R.F., Raveendran G., Helmer G., Yannopoulos D., et al: Avoiding the learning curve for Transcatheter aortic valve replacement. Cardiol Res Pract 2017; 2017: pp. 7524925
    6. [6]Leon M.B., Piazza N., Nikolsky E., Blackstone E.H., Cutlip D.E., Kappetein A.P., et al: Standardized endpoint definitions for Transcatheter aortic valve implantation clinical trials: a consensus report from the valve academic research consortium. J Am Coll Cardiol 2011; 57: pp. 253-269
    7. [7]Mehran R., Rao S.V., Bhatt D.L., Gibson C.M., Caixeta A., Eikelboom J., et al: Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the bleeding academic research consortium. Circulation 2011; 123: pp. 2736-2747
    8. [8]Nijenhuis V.J., Bennaghmouch N., van Kuijk J.P., Capodanno D., and ten Berg J.M.: Antithrombotic treatment in patients undergoing transcatheter aortic valve implantation (TAVI). Thromb Haemost 2015; 113: pp. 674-685
    9. [9]Nijenhuis V.J., Stella P.R., Baan J., Brueren B.R., de Jaegere P.P., den Heijer P., et al: Antithrombotic therapy in patients undergoing TAVI: an overview of Dutch hospitals. Neth. Hear. J. 2014; 22: pp. 64-69
    10. [10]Leon M.B., Smith C.R., Mack M., Miller D.C., Moses J.W., Svensson L.G., et al: Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010; 363: pp. 1597-1607
    11. [11]Smith C.R., Leon M.B., Mack M.J., Miller D.C., Moses J.W., Svensson L.G., et al: Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011; 364: pp. 2187-2198
    12. [12]Rodes-Cabau J., Masson J.B., Welsh R.C., Garcia Del Blanco B., Pelletier M., Webb J.G., et al: Aspirin versus aspirin plus Clopidogrel as antithrombotic treatment following Transcatheter aortic valve replacement with a balloon-expandable valve: the ARTE (aspirin versus aspirin . JACC Cardiovasc Interv 2017; 10: pp. 1357-1365
    13. [13]Merie C., Kober L., Skov Olsen P., Andersson C., Gislason G., Skov Jensen J., et al: Association of warfarin therapy duration after bioprosthetic aortic valve replacement with risk of mortality, thromboembolic complications, and bleeding. JAMA 2012; 308: pp. 2118-2125
    14. [14]Nishimura R.A., Otto C.M., Bonow R.O., Carabello B.A., Erwin J.P., Fleisher L.A., et al: 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol 2017; 70: pp. 252-289
    15. [15]Ng K.H., Hart R.G., and Eikelboom J.W.: Anticoagulation in patients aged ≥ . Cardiol Ther 2013; 2: pp. 135-149
    16. [16]Sharma M., Cornelius V.R., Patel J.P., Davies J.G., and Molokhia M.: Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: systematic review and meta-analysis. Circulation 2015; 132: pp. 194-204
    17. [17]Pokorney S.D., Simon D.N., Thomas L., Fonarow G., Jowey P.R., Chang P., et al: Patients' time in therapeutic range on warfarin among US patients with atrial fibrillation: results from ORBIT-AF registry. Am Heart J 2015; 170: pp. 141-148
    18. [18]Rose A.J., Hylek E.M., Ozonoff A., Ash A.S., Reisman J.I., and Berlowitz D.R.: Risk-adjusted percent time in therapeutic range as a quality indicator for outpatient oral anticoagulation: results of the veterans affairs study to improve anticoagulation (VARIA). Circ Cardiovasc Qual Outcomes 2011; 4: pp. 22-29

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