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Managing Patients With an Indication for Anticoagulant Therapy After Transcatheter Aortic Valve Implantation

Published:October 29, 2012DOI:https://doi.org/10.1016/j.amjcard.2012.09.023
      Patients who undergo transcatheter aortic valve implantation are generally discharged on dual-antiplatelet therapy. However, many of these patients also have indications for anticoagulant therapy, and it is unclear what the best antithrombotic strategy is in these cases. Data from 360 patients who underwent transcatheter aortic valve implantation were retrospectively analyzed, of whom 60 (16.7%) had indications for anticoagulant treatment, mainly because of atrial fibrillation. The antithrombotic regimen was decided according to clinical evaluation of thrombotic and hemorrhagic risk; most of these patients (n = 43) were discharged with warfarin plus a single antiplatelet drug. Their outcomes were compared to those in a group with no indications for anticoagulation (n = 300) treated with dual-antiplatelet therapy. During the follow-up period (median 11 months), 53 patients (15%) died; mortality was not associated with antithrombotic regimen. The incidence of cerebral events or intracranial hemorrhage (4.6% and 1.1%, respectively) was low in the study population, and no significant differences were detected between groups; the bleeding rate was also unaffected by antithrombotic therapy. In conclusion, when anticoagulation is indicated after transcatheter aortic valve implantation, many variables must be taken into account. The most frequent scenario in this study was patients in atrial fibrillation, most of whom were discharged with warfarin plus a single antiplatelet medication. When bleeding was a concern, especially in the absence of coronary disease, warfarin alone was prescribed. These results suggest that this approach is safe, but data from larger, randomized studies are needed.
      Common practice in cardiac surgery is to administer anticoagulants for ≥3 months after prosthetic valve implantation, waiting for healing of the prosthesis and endothelialization.
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      • Carabello B.A.
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      • Shanewise J.S.
      2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
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      • Iung B.
      • Bjornstad H.
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      • Hall R.J.
      • Vahanian A.
      Recommendations for the management of patients after heart valve surgery.
      Similarly, it has been demonstrated that percutaneously implanted aortic prosthetic valves soon become covered by fibrin, which is then replaced by smooth muscle cells and finally by endothelium, thereby incorporating the foreign body into the surrounding tissues and restoring a normal interface for blood.
      • Noble S.
      • Asgar A.
      • Cartier R.
      • Virmani R.
      • Bonan R.
      Anatomo-pathological analysis after CoreValve ReValving system implantation.
      This process is estimated to be completed within a few months, but until the prosthetic material is completely endothelialized, there is concern that small thrombi may detach from the valve and cause cerebral ischemia. To protect patients from this possible complication during the first months after intervention, dual-antiplatelet therapy (DAT) is generally started before the intervention and continued for 3 to 6 months after the procedure, an approach that is empirically derived from coronary artery stenting.
      • Whitlock R.P.
      • Sun J.C.
      • Fremes S.E.
      • Rubens F.D.
      • Teoh K.H.
      Antithrombotic and thrombolytic therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.
      After publication of the results of the Placement of Aortic Transcatheter Valves (PARTNER) trial,
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      • Smith C.R.
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      • Miller D.C.
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      • Webb J.G.
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      • Makkar R.R.
      • Brown D.L.
      • Block P.C.
      • Guyton R.A.
      • Pichard A.D.
      • Bavaria J.E.
      • Herrmann H.C.
      • Douglas P.S.
      • Petersen J.L.
      • Akin J.J.
      • Anderson W.N.
      • Wang D.
      • Pocock S.
      Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.
      • Smith C.R.
      • Leon M.B.
      • Mack M.J.
      • Miller D.C.
      • Moses J.W.
      • Svensson L.G.
      • Tuzcu E.M.
      • Webb J.G.
      • Fontana G.P.
      • Makkar R.R.
      • Williams M.
      • Dewey T.
      • Kapadia S.
      • Babaliaros V.
      • Thourani V.H.
      • Corso P.
      • Pichard A.D.
      • Bavaria J.E.
      • Herrmann H.C.
      • Akin J.J.
      • Anderson W.N.
      • Wang D.
      • Pocock S.J.
      Transcatheter versus surgical aortic-valve replacement in high-risk patients.
      which showed a non-negligible incidence of periprocedural strokes and cerebral ischemic events, even more emphasis is being placed on identifying and preventing cerebral embolization.
      • Astarci P.
      • Glineur D.
      • Kefer J.
      • D'Hoore W.
      • Renkin J.
      • Vanoverschelde J.L.
      • El Khoury G.
      • Grandin C.
      Magnetic resonance imaging evaluation of cerebral embolization during percutaneous aortic valve implantation: comparison of transfemoral and trans-apical approaches using Edwards Sapiens valve.
      • Ghanem A.
      • Muller A.
      • Nahle C.P.
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      • Werner N.
      • Hammerstingl C.
      • Schild H.H.
      • Schwab J.O.
      • Mellert F.
      • Fimmers R.
      • Nickenig G.
      • Thomas D.
      Risk and fate of cerebral embolism after transfemoral aortic valve implantation: a prospective pilot study with diffusion-weighted magnetic resonance imaging.
      However, many of these patients also have indications for long-term anticoagulant therapy, mainly because of the high incidence of atrial fibrillation in this elderly population. It is unclear what the best therapeutic approach is in these patients.

      Methods

      To assess this issue, we retrospectively evaluated patients who underwent transcatheter aortic valve implantation (TAVI) at our institution from November 2007 to October 2011, focusing on outcomes according to antithrombotic therapy at discharge. Patients with indications for anticoagulant treatment were considered the study group, while the others served as a control group.
      Patients were considered eligible for TAVI if they had severe, symptomatic aortic stenosis and were considered at high surgical risk according to current recommendations.
      • Vahanian A.
      • Alfieri O.
      • Al-Attar N.
      • Antunes M.
      • Bax J.
      • Cormier B.
      • Cribier A.
      • De Jaegere P.
      • Fournial G.
      • Kappetein A.P.
      • Kovac J.
      • Ludgate S.
      • Maisano F.
      • Moat N.
      • Mohr F.
      • Nataf P.
      • Pierard L.
      • Pomar J.L.
      • Schofer J.
      • Tornos P.
      • Tuzcu M.
      • van Hout B.
      • Von Segesser L.K.
      • Walther T.
      Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI).
      Both self-expanding devices and balloon-expandable prostheses were implanted. In the absence of contraindications, patients were pretreated with aspirin and clopidogrel (with a 300-mg loading dose on the day before the procedure) and were discharged on DAT for a period of 3 to 6 months, after which only aspirin was recommended. Transfemoral access was preferred whenever feasible; in the case of transapical, transaortic, or transaxillary access, only aspirin was administered before the procedure. Heparin was administered periprocedurally to all patients, according to standard practice, to prevent catheter thrombosis.
      In patients with concomitant indications for anticoagulant therapy, treatment was decided on an individual basis according to the clinical evaluation of the risk for thrombotic and hemorrhagic events. When anticoagulation was thought to be necessary, patients were treated with low–molecular weight heparin for the periprocedural period and then discharged on warfarin therapy.
      Clinical and echocardiographic evaluation was performed at admission, before discharge, and later at scheduled outpatient visits at 30 days, 6 months, 1 year, and subsequently once a year. Data were prospectively entered in a dedicated database; personnel who adjudicated adverse events were unblinded to antithrombotic therapy. All end points were defined according to the Valve Academic Research Consortium definitions.
      • Leon M.B.
      • Piazza N.
      • Nikolsky E.
      • Blackstone E.H.
      • Cutlip D.E.
      • Kappetein A.P.
      • Krucoff M.W.
      • Mack M.
      • Mehran R.
      • Miller C.
      • Morel M.A.
      • Petersen J.
      • Popma J.J.
      • Takkenberg J.J.
      • Vahanian A.
      • van Es G.A.
      • Vranckx P.
      • Webb J.G.
      • Windecker S.
      • Serruys P.W.
      Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium.
      Normally distributed continuous variables are expressed as mean ± SD, and medians and interquartile ranges (IQRs) are used to report variables with skewed distributions; the normality of the distributions of continuous variables was tested using Kolmogorov-Smirnov goodness-of-fit tests. Categorical variables are expressed as absolute numbers and percentages. Continuous variables were compared using Student's t tests or Wilcoxon-Mann-Whitney tests for normally or non-normally distributed variables, respectively. When multiple comparisons were made, analysis of variance with Fisher's least-significant-difference post hoc tests was used. Categorical variables were compared using chi-square or Fisher's exact tests as appropriate. Two-sided p values <0.05 were used as a threshold for statistical significance.

      Results

      In the study period, 360 patients underwent TAVI at our institution using the Medtronic CoreValve (n = 144 [40%]; Medtronic, Inc., Minneapolis, Minnesota) or Edwards Sapien (n = 216 [60%]; Edwards Lifesciences, Irvine, California). Of these, 60 patients (16.7%) had ≥1 indication for anticoagulant therapy, mainly because of atrial fibrillation, which was present in 15.6% of the overall population (Table 1).
      Table 1Indications for anticoagulant therapy
      IndicationFrequency
      Percentages are calculated on the basis of the overall population (n = 360).
      Atrial fibrillation56 (15.6%)
      Previous deep vein thrombosis7 (1.9%)
      Mechanical mitral valve prosthesis3 (0.8%)
      Previous arterial thrombosis1 (0.3%)
      Percentages are calculated on the basis of the overall population (n = 360).
      All patients in atrial fibrillation had high CHADS-VASc scores (mean 5 ± 1.2), reflecting the high prevalence of heart failure, advanced age, and other co-morbidities in this population. In contrast, advanced age and frailty, which are almost universal in patients with TAVI, represent important risk factors for bleeding.
      According to the clinical evaluation of thrombotic and hemorrhagic risk, these 60 patients were discharged with different therapeutic regimens: 43 (71.7%) with an anticoagulant plus 1 antiplatelet agent, of whom 11 (18.3%) had an anticoagulant plus aspirin and 32 (53.4%) had an anticoagulant plus clopidogrel; 14 (23.3%) with an anticoagulant without any antiplatelet therapy; 2 (3.3%) on DAT; and 1 (1.7%) with an anticoagulant plus DAT because of concomitant coronary artery revascularization with a bare-metal stent.
      We limited most of our analyses to a comparison between a control group, discharged on DAT for 3 to 6 months (n = 300), and the group of patients receiving therapy with an anticoagulant and a single antiplatelet drug (n = 43).
      Baseline clinical characteristics of the 2 groups are listed in Table 2. Compared to patients on DAT, insulin-dependent diabetes mellitus and a history of cerebrovascular or coronary artery disease were slightly less prevalent in subjects with an anticoagulant and a single antiplatelet drug. No statistically significant differences were found between groups regarding the type and size of prosthesis implanted or the type of vascular access adopted; procedural variables are summarized in Table 3.
      Table 2Baseline clinical characteristics
      VariableOverall (n = 360)DAT (n = 300)Anticoagulant Plus Single Antiplatelet (n = 43)p Value
      Age (yrs)79 ± 779 ± 880 ± 60.232
      Men180 (50%)156 (52%)21 (49%)0.077
      Body surface area (m2)1.77 ± 0.181.76 ± 0.181.82 ± 0.20.300
      Body mass index (kg/m2)26 ± 526 ± 527 ± 50.627
      Diabetes mellitus108 (30%)94 (31%)8 (19%)0.085
      Insulin-dependent diabetes mellitus36 (10%)35 (12%)00.013
      Statistically significant (p <0.05).
      Hypertension269 (76%)219 (73%)38 (88%)0.032
      Statistically significant (p <0.05).
      Chronic renal failure117 (33%)103 (37%)12 (28%)0.388
      Chronic hemodialysis13 (4%)10 (3%)2 (5%)0.670
      Creatinine clearance52.2 ± 24.152 ± 24.654.8 ± 23.20.481
      Hemoglobin (g/dl)12 ± 1.712 ± 1.812.2 ± 1.60.521
      Chronic obstructive pulmonary disease131 (37%)110 (37%)17 (40%)0.728
      Permanent pacemaker30 (9%)23 (8%)7 (16%)0.082
      Cerebrovascular disease42 (15%)49 (16%)2 (5%)0.043
      Statistically significant (p <0.05).
      Peripheral arterial disease108 (31%)92 (31%)11 (26%)0.472
      Coronary artery disease145 (42%)134 (46%)11 (26%)0.017
      Statistically significant (p <0.05).
      Previous acute myocardial infarction76 (21%)69 (26%)7 (16%)0.316
      Previous percutaneous coronary intervention72 (20%)67 (22%)5 (12%)0.105
      Previous coronary artery bypass graft74 (21%)66 (22%)8 (19%)0.605
      Previous aortic bioprosthesis5 (2%)4 (1%)1 (2%)0.100
      “Porcelain” aorta63 (19%)55 (19%)7 (16%)0.652
      Aortic annulus (mm)23.5 ± 1.923.5 ± 1.823.5 ± 1.90.945
      Aortic valve area (cm2)0.7 ± 0.20.7 ± 0.20.7 ± 0.20.858
      Mean aortic gradient (mm Hg)53 ± 1752 ± 1756 ± 150.564
      Maximal aortic gradient (mm Hg)85 ± 2584 ± 2490 ± 230.452
      Peak aortic valve velocity (cm/s)461 ± 250458 ± 245474 ± 2400.487
      Left ventricular ejection fraction (%)52 ± 1352 ± 1352 ± 120.697
      Left ventricular ejection fraction ≤35%51 (14%)42 (14%)6 (14%)0.974
      New York Heart Association class III or IV239 (68%)196 (66%)31 (72%)0.769
      Aortic regurgitation 3 to 4+47 (14%)37 (13%)7 (17%)0.845
      Logistic European System for Cardiac Operative Risk Evaluation score19.5 (11.4–31.2)19.5 (11.4–31.4)20.3 (11–30.5)0.977
      Society of Thoracic Surgeons score6 (4–10)6 (4–10)6 (4.3–8.5)0.985
      Iliofemoral minimal luminal diameter (therapeutic access)7.5 ± 1.237.5 ± 1.227.4 ± 1.260.987
      CHADS-VASc score5 ± 1.24.9 ± 1.34.9 ± 1.20.182
      Data are expressed as mean ± SD, as number (percentage), or as median (IQR).
      Statistically significant (p <0.05).
      Table 3Procedural variables
      VariableOverall (n = 360)DAT (n = 300)Anticoagulant Plus Single Antiplatelet (n = 43)p Value
      Valve type
       Edwards216 (60.5%)187 (62.3%)23 (53.5%)0.285
      Sapien101 (26.8%)89 (28.2%)10 (23.2%)0.612
      Sapien XT115 (33.7%)98 (34.1%)13 (30.2%)0.612
       Medtronic CoreValve141 (39.5%)113 (37.7%)20 (46.5%)0.209
      Valve size (mm)
       2390 (25.2%)77 (25.7%)9 (20.9%)0.300
       26176 (49.3%)150 (50%)22 (51.2%)0.763
       2990 (25.2%)73 (24.3%)12 (27.9%)0.649
      Access
       Transfemoral280 (82.1%)237 (82.7%)36 (83.7%)0.853
       Transapical24 (7%)20 (7%)2 (4.7%)0.570
       Transaxillary35 (10.3%)28 (9.8%)5 (11.6%)0.703
       Transaortic3 (0.8%)2 (0.7%)1 (2.3%)0.294
      Sheath size (Fr)19.6 ± 2.319.6 ± 2.319.4 ± 2.30.655
      Elective surgical closure69 (20.2%)55 (19.2%)10 (23.3%)0.529
      Failure of percutaneous closure22 (7.9%)17 (7.2%)4 (12.1%)0.607
      Heparin (U/kg)75 ± 2176 ± 2070 ± 220.767
      Prevalvuloplasty288 (80.7%)246 (82%)38 (88.4%)0.639
      Postdilatation64 (18.4%)47 (16%)12 (28.6%)0.296
      Data are expressed as mean ± SD or as number (percentage).
      Median follow-up was 11 months (IQR 6 to 15), and during this period, 53 patients (15% of the total population) died; cardiovascular mortality accounted for about half of these cases. Outcomes are listed in detail in Table 4; no outcomes were found to be statistically different between the groups. Figure 1 shows the mortality rate at 1 year for patients receiving DAT compared to warfarin and a single antiplatelet drug. The only patient receiving “triple therapy” died because of cardiogenic shock 5 days after the procedure. We found no difference in mortality between patients taking or not taking anticoagulant therapy (13.8% vs 15.4%, p = 0.757) or considering patients in atrial fibrillation versus sinus rhythm (14.3% vs 15.3%, p = 0.848).
      Table 4Clinical outcomes in the hospital and during follow-up
      VariableOverall (n = 360)DAT (n = 300)Anticoagulant Plus Single Antiplatelet (n = 43)p Value
      Follow up (days)331 (121–452)330 (121–467)368 (245–417)0.247
      Overall mortality53 (15%)46 (15.5%)7 (16.3%)0.894
       Days to death146 (45–365)137 (44–355)364 (187–417)0.098
       Cardiovascular mortality27 (7.6%)24 (8.1%)3 (7%)0.802
       In-hospital mortality14 (4.1%)14 (4.9%)00.139
      Myocardial infarction7 (2%)6 (2%)1 (2.4%)0.890
      Cerebrovascular events16 (4.6%)14 (4.8%)2 (4.8%)1.000
       Stroke9 (2.5%)8 (2.7%)1 (2.4%)1.000
       Transient ischemic attack7 (1.9%)6 (2%)1 (2.4%)0.613
       Intracranial bleeding4 (1.1%)3 (1%)1 (2.4%)0.416
      Life-threatening bleeding83 (24.3%)70 (24.4%)10 (23.3%)0.889
      Major bleeding107 (31.4%)95 (33.1%)11 (25.6%)0.284
      Minor bleeding19 (5.6%)16 (5.6%)2 (4.7%)1.000
      Hemoglobin decrease (g/dL)2.7 ± 1.62.7 ± 1.72.6 ± 1.50.317
      Transfusion149 (43.8%)129 (45.1%)16 (37.2%)0.331
      Transfused red blood cells0 (0–2)0 (0–2)0 (0–2)0.223
      Acute kidney injury110 (32.1%)92 (31.9%)16 (37.2%)0.492
       Stage 164 (18.8%)53 (18.5%)10 (23.3%)0.456
       Stage 216 (4.7%)14 (4.9%)2 (4.7%)1.000
       Stage 326 (9.7%)23 (9.4%)3 (14%)1.000
       Renal replacement20 (5.6%)17 (5.7%)3 (7%)0.146
      Major vascular complications51 (15%)44 (15.3%)7 (16.3%)0.873
      Minor vascular complications34 (9.9%)25 (8.7%)8 (18.6%)0.055
      Aortic dissection3 (0.9%)3 (1%)00.501
      Device success323 (94.2%)268 (92.7%)41 (95.3%)0.542
      Freedom from combined safety end point (30 days)223 (67.8%)184 (66.9%)30 (71.4%)0.727
      In-hospital stay (days)6 (5–9)6 (5–9)7 (5–9)0.684
      Data are expressed as mean ± SD, as number (percentage), or as median (IQR).
      Figure thumbnail gr1
      Figure 1One-year mortality according to antithrombotic therapy. AC = anticoagulant.
      The incidence of cerebrovascular events during follow-up was 4.6% (16 patients); stroke occurred in 9 patients (2.5%) and transient ischemic attacks in 7 (1.9%). Of these 16 events, 9 (56%) occurred during the hospital stay and 7 (44%) after discharge. During the periprocedural period, transient ischemic attacks were more common than stroke, occurring respectively in 6 and 3 patients. The median time to cerebrovascular event was 74 days (IQR 2 to 233): 2 days (IQR 2 to 8) to transient ischemic attack and 223 days (IQR 74 to 517) to stroke. Mortality was significantly higher in patients who experienced cerebrovascular events during the follow-up period (68.8% vs 12.9%, p <0.001).
      Therapy at discharge was not found to be predictive of stroke or transient ischemic attack; the incidence of cerebrovascular events was 4.8% in the control group and in patients with an anticoagulant and a single antiplatelet medication, whereas no such events were reported in patients discharged with warfarin therapy only (p = 0.945). Atrial fibrillation was not associated with cerebrovascular events (4.7% in patients in sinus rhythm vs 3.8% in patients with AF, p = 0.754). Among these 9 strokes, 4 cases of intracranial bleeding occurred, all of which were fatal; 3 occurred in the control group and the other in a patient taking warfarin and clopidogrel (p = NS).
      The bleeding rate did not significantly differ among groups of patients. The only patient who was receiving triple therapy experienced a life-threatening bleeding, which was not the direct cause of death. Major vascular complications were not associated with the therapeutic regimen. Three cases of aortic dissection occurred, all in the DAT group. Also, no cases of prosthetic valve thrombosis were documented during the study period.
      Analyzing patients discharged with an anticoagulant plus a single antiplatelet medication, no significant differences were found in survival, neurologic events, bleeding rate, or cardiovascular complications between patients receiving clopidogrel (n = 32) or aspirin (n = 11).
      The follow-up period was significantly shorter for patients who were discharged with warfarin therapy without antiplatelet drugs (104 days, IQR 68 to 247); none of these 14 patients died during follow-up or experienced cerebrovascular events, and the bleeding rate was not different from other groups.

      Discussion

      Among candidates for TAVI, an indication for anticoagulant therapy, mainly because of atrial fibrillation, is a frequent issue and poses a significant clinical problem, as these patients are often at high risk for developing ischemic and bleeding events, either as procedural complications or spontaneously. The standard practice of administering DAT, even if widely accepted, is not based on robust clinical evidence and has indeed been questioned in a recent small randomized trial, which showed no benefit of DAT over aspirin alone.
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      Dual antiplatelet therapy versus aspirin alone in patients undergoing transcatheter aortic valve implantation.
      In contrast, some investigators have also hypothesized that antiplatelet therapy could impair healing of possible subclinical aortic tears, thereby predisposing patients to delayed aortic rupture.
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      Delayed mortality from aortic dissection post transcatheter aortic valve implantation (TAVI): the tip of the iceberg.
      On the basis of clinical experience, we believe that when anticoagulation is necessary, triple therapy with aspirin, clopidogrel, and warfarin is not justified after TAVI, unless concomitant coronary revascularization with stent placement is performed.
      In these cases, many variables were taken into account to determine therapy, including indication for anticoagulation, age, general status, frailty, compliance, and concomitant coronary artery disease.
      In general, the most frequent situation is represented by patients in atrial fibrillation, typically with a high thromboembolic risk; new-onset atrial fibrillation can also occur after the procedure and is associated with a higher incidence of stroke or systemic embolism. In this situation, a low threshold for starting anticoagulant therapy is recommended, even if precise guidelines regarding postoperative atrial fibrillation are lacking.
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      Incidence, predictive factors, and prognostic value of new-onset atrial fibrillation following transcatheter aortic valve implantation.
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      Frequency and causes of stroke during or after transcatheter aortic valve implantation.
      At the beginning of our TAVI experience, we were quite concerned with completely withholding DAT after valve implantation, but later, we started to discharge some patients with warfarin only; this is why this group had a small number and a shorter follow-up period. We have always prescribed antiplatelet therapy to patients with concomitant coronary artery disease, and also if they are clinically stable. However, recently issued guidelines for antithrombotic therapy from the American College of Chest Physicians recommend anticoagulant plus antiplatelet treatment only in high-risk patients, such as soon after stent implantation.
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      So, according to these guidelines, our strategy may appear even too unbalanced toward protection from thrombotic risk.
      Previous venous thrombosis is another not infrequent indication for anticoagulation in these patients; however, as recently suggested, antiplatelet therapy alone may prevent recurrences of thrombosis.
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      In general, we believe that patients who have indications for long-term anticoagulation should continue with this therapy irrespective of the TAVI procedure. If the risk for bleeding by adding an antiplatelet medication is deemed too high, warfarin alone may be sufficient therapy. When poor compliance to anticoagulant therapy is expected, or managing international normalized ratios is difficult, DAT may be a valuable option.
      Our average follow-up was long enough to ensure that patients were observed for the period considered necessary for valve endothelialization and thus the time that these patients are most at risk for stroke. It must be noted, however, that in our experience, the incidence of cerebrovascular events is quite low, which makes it more difficult to ascertain a difference in the risk between treatment groups. Compared to incidence rates reported in recent publications, our rate of mortality and cerebrovascular events appears low
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      : overall mortality at 1-year is generally reported to range from 15% to 25% (with cardiovascular mortality accounting for about half of these cases),
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      One-year outcomes of cohort 1 in the Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registry: the European registry of transcatheter aortic valve implantation using the Edwards SAPIEN valve.
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      Our incidence of major bleeding events at 1 year is instead higher than usually reported (3% to 15% in most recent reports).
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      • Miller D.C.
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      • Bavaria J.E.
      • Herrmann H.C.
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      • Anderson W.N.
      • Wang D.
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      Transcatheter versus surgical aortic-valve replacement in high-risk patients.
      • Gilard M.
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      • Chevreul K.
      • Fajadet J.
      • Leprince P.
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      • Lievre M.
      • Prat A.
      • Teiger E.
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      • Himbert D.
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      • Carrie D.
      • Albat B.
      • Cribier A.
      • Rioufol G.
      • Sudre A.
      • Blanchard D.
      • Collet F.
      • Dos Santos P.
      • Meneveau N.
      • Tirouvanziam A.
      • Caussin C.
      • Guyon P.
      • Boschat J.
      • Le Breton H.
      • Collart F.
      • Houel R.
      • Delpine S.
      • Souteyrand G.
      • Favereau X.
      • Ohlmann P.
      • Doisy V.
      • Grollier G.
      • Gommeaux A.
      • Claudel J.P.
      • Bourlon F.
      • Bertrand B.
      • Van Belle E.
      • Laskar M.
      Registry of transcatheter aortic-valve implantation in high-risk patients.
      • Tamburino C.
      • Capodanno D.
      • Ramondo A.
      • Petronio A.S.
      • Ettori F.
      • Santoro G.
      • Klugmann S.
      • Bedogni F.
      • Maisano F.
      • Marzocchi A.
      • Poli A.
      • Antoniucci D.
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      • De Carlo M.
      • Fiorina C.
      • Ussia G.P.
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      Beyond the risk for stroke, another reason for the practice of treating TAVI patients with DAT is the initial observation of cases of severe thrombocytopenia after the procedure in patients treated with aspirin only; it was postulated that platelet activation due to interaction with the prosthesis may cause platelet consumption, and it was therefore suggested that a stronger platelet inhibition could avoid this side effect.
      • Grube E.
      • Laborde J.C.
      • Gerckens U.
      • Felderhoff T.
      • Sauren B.
      • Buellesfeld L.
      • Mueller R.
      • Menichelli M.
      • Schmidt T.
      • Zickmann B.
      • Iversen S.
      • Stone G.W.
      Percutaneous implantation of the CoreValve self-expanding valve prosthesis in high-risk patients with aortic valve disease: the Siegburg first-in-man study.
      Mild to moderate thrombocytopenia is indeed not an infrequent finding, also in patients receiving DAT. In our experience, however, we tend to withdraw clopidogrel as a possible cause itself of the low platelet count, and the abnormality usually resolves in a few days. However, we do not have enough data to establish a precise relation between the therapeutic regimen and thrombocytopenia.
      This study was obviously limited by its retrospective and nonrandomized nature and lacked the power to detect differences in embolic accidents or rare events such as intracerebral bleeds. Moreover, the number of patients treated with warfarin alone was too small to draw any firm conclusions; also, as explained previously, this therapeutic regimen was prescribed mainly in the most recent cases, so there may be a bias due to the learning curve. However, we believe that it is noteworthy that patients discharged on anticoagulant therapy alone experienced no death or cerebrovascular events during the follow-up period. Although this is insufficient to conclude that this therapeutic regimen is safe and effective, it does justify more extensive studies on the optimal antithrombotic regimen after TAVI, especially considering that current practice itself is not based on robust evidence.

      Disclosures

      The authors have disclosed no conflicts of interest.

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