Author + information
- Received March 7, 2016
- Revision received June 10, 2016
- Accepted June 19, 2016
- Published online August 22, 2016.
- Omar Abdul-Jawad Altisent, MDa,
- Eric Durand, MD, PhDb,
- Antonio J. Muñoz-García, MD, PhDc,
- Luis Nombela-Franco, MDd,
- Asim Cheema, MDe,
- Joelle Kefer, MD, PhDf,
- Enrique Gutierrez, MDg,
- Luis M. Benítez, MDh,
- Ignacio J. Amat-Santos, MDi,
- Vicenç Serra, MDj,
- Helene Eltchaninoff, MDb,
- Sami M. Alnasser, MDe,
- Jaime Elízaga, MD, PhDg,
- Antonio Dager, MDh,
- Bruno García del Blanco, MDj,
- Maria del Rosario Ortas-Nadal, MDa,
- Josep Ramon Marsalj,k,
- Francisco Campelo-Parada, MDa,
- Ander Regueiro, MDa,
- Maria del Trigo, MDa,
- Eric Dumont, MDa,
- Rishi Puri, MBBS, PhDa and
- Josep Rodés-Cabau, MDa,∗ ()
- aCardiology Department, Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada
- bCardiology Department, University Hospital of Rouen, Hospital Charles Nicolle, Rouen, France
- cCardiology Department, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
- dCardiology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain
- eCardiology Department, St. Michael’s Hospital, Toronto University, Toronto, Ontario, Canada
- fCardiology Department, Saint Luc University Hospital, Brussels, Belgium
- gCardiology Department, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
- hCardiology Department, Clìnica de Occidente de Cali, Valle del Cauca, Colombia
- iCardiology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
- jCardiology Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
- kCIBER of Epidemiology and Public Health (CIBERESP), Barcelona, Spain
- ↵∗Reprint requests and correspondence:
Dr. Josep Rodés-Cabau, Quebec Heart & Lung Institute, Laval University, 2725 chemin Ste-Foy, Quebec City, Quebec G1V 4G5, Canada.
Objectives The study sought to examine the risk of ischemic events and bleeding episodes associated with differing antithrombotic strategies in patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant atrial fibrillation (AF).
Background Guidelines recommend antiplatelet therapy (APT) post-TAVR to reduce the risk of stroke. However, data on the efficacy and safety of this recommendation in the setting of a concomitant indication for oral anticoagulation (due to atrial fibrillation [AF]) with a vitamin K antagonist (VKA) are scarce.
Methods A multicenter evaluation comprising 621 patients with AF undergoing TAVR was undertaken. Post-TAVR prescriptions were used to determine the antithrombotic regimen used according to the following 2 groups: monotherapy (MT) with VKA (n = 101) or multiple antithrombotic therapy (MAT) with VKA plus 1 or 2 antiplatelet agents (aspirin or clopidogrel; n = 520). Endpoint definitions were in accordance with Valve Academic Research Consortium-2 criteria. The rate of stroke, major adverse cardiovascular events (stroke, myocardial infarction, or cardiovascular death), major or life-threatening bleeding events, and death were assessed by a Cox multivariate model regression survival analysis according to the antithrombotic regime used.
Results During a median follow-up of 13 months (interquartile range: 3 to 31 months) there were no differences between groups in the rate of stroke (MT: 5%, MAT: 5.2%; adjusted hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 0.45 to 3.48; p = 0.67), major adverse cardiovascular events (MT: 13.9%, MAT: 16.3%; adjusted HR: 1.33; 95% CI: 0.75 to 2.36; p = 0.33), and death (MT 22.8%, MAT: 19.2%; adjusted HR: 0.93; 95% CI: 0.58 to 1.50; p = 0.76). A higher risk of major or life-threatening bleeding was found in the MAT group (MT: 14.9%, MAT: 24.4%; adjusted HR: 1.85; 95% CI: 1.05 to 3.28; p = 0.04). These results remained similar when patients receiving VKA plus only 1 antiplatelet agent (n = 463) were evaluated.
Conclusions In TAVR recipients prescribed VKA therapy for AF, concomitant antiplatelet therapy use appears not to reduce the incidence of stroke, major adverse cardiovascular events, or death, while increasing the risk of major or life-threatening bleeding.
Current guidelines recommend antiplatelet therapy (APT) following transcatheter aortic valve replacement (TAVR) to reduce the risk of stroke (1,2). However, up to 30% of patients undergoing TAVR have an indication for vitamin K antagonist (VKA) therapy, largely due to concomitant atrial fibrillation (AF) (3). This subgroup represents a particularly high-risk population for ischemic and bleeding events, as antithrombotic agents cumulatively increase bleeding risk, which in turn adversely impacts morbidity and mortality (4,5). Therefore, the optimal antithrombotic regimen in TAVR recipients requiring VKA for underlying AF remains unclear (1). Various empirical antithrombotic regimens exist, yet no published study has evaluated the best strategy for such patients. Given the known vast differences between conventional TAVR recipients and the patients previously evaluated in AF trials, extrapolating data across these populations is thus fraught with limitations. The delicate balance between ischemic events and stroke prevention although concomitantly minimizing bleeding risk, remains an important yet unanswered clinical question following TAVR (6).
We undertook a multicenter study aimed at evaluating the risk of cardiovascular and bleeding events in a real-world TAVR setting amongst patients prescribed 2 different antithrombotic strategies in the setting of AF. In particular, the addition of an antiplatelet agent to VKA following TAVR was compared with a more conservative strategy that maintained VKA monotherapy (MT).
Study population, antithrombotic regimens, and data
This multicenter study collected data from 12 centers from patients who underwent TAVR between 2007 and 2015. The indication for TAVR and approach were assessed by each center’s heart team, and TAVR procedures were performed as previously described (7). Patients were eligible for inclusion if they had undergone TAVR, had AF, and were prescribed VKA (with or without antiplatelet agents) before hospital discharge. A total of 2,186 patients underwent TAVR. Of these, 1,565 were excluded for the following reasons: no antecedent history of AF or not prescribed VKA therapy (n = 1,496), immediate procedural death (n = 68 patients), and no procedural or follow-up information (n = 28). The final study population consisted of 621 patients. Prescriptions for VKA or aspirin or clopidogrel pre-hospital discharge were used to retrospectively classify patients according to 1 of the following drug regimen groups: MT with VKA alone (n = 101); multiple antithrombotic therapy (MAT) with VKA plus 1 or 2 antiplatelet agents (aspirin or clopidogrel; n = 520). The MAT group comprised patients prescribed double therapy (DT), including patients with VKA plus only 1 antiplatelet agent as recommended by guidelines (n = 463) (1,2), and a triple therapy (TT) group including patients with VKA plus aspirin and clopidogrel (n = 57). The criteria for the use of a specific antithrombotic strategy was as follows: 5 centers prescribed VKA plus at least 1 antiplatelet to all patients; 1 center prescribed VKA plus at least 1 antiplatelet agent until December 2011, thereafter patients were discharged with VKA alone if they had no other indication for APT; in all the others centers the strategy was at the treating physician’s discretion.
All data were prospectively collected in a dedicated database. Gathered data included the main baseline clinical, echocardiographic, procedural characteristics, and in-hospital and follow-up outcomes with special attention to ischemic events and bleeding episodes requiring hospitalization. For bleeding events, fluctuations in hemoglobin levels, red cell transfusions, and a requirement for intensive care unit or surgical treatment to control bleeding were collected. Outcomes measures were recorded at the time of TAVR. Follow-up data was obtained by case note revision or telephone interviews. Changes in the antithrombotic therapies were recorded, and duration of treatment was calculated individually. All studies were performed in accordance with the local ethics committee of each center, and all patients signed informed consent forms before the procedures.
Outcomes measures (ischemic event definition and bleeding episode definition)
Efficacy outcomes were defined as stroke, myocardial infarction, cardiovascular death, and death from any cause. The major cardiovascular combined endpoint of stroke, myocardial infarction, or cardiovascular death was also assessed. Stroke, myocardial infarction and periprocedural events were defined according to the Valve Academic Research Consortium-2 (VARC-2) criteria (8). Safety outcomes were defined as bleeding episodes. Each bleeding episode was classified separately according to VARC-2 and Bleeding Academic Research Consortium (BARC) criteria (scoring 1 to 5, where 1 is minimum and 5 represents fatal bleeding) (9). We recorded bleeding episodes classified as major or life-threatening bleeding (LTB) following the VARC-2 criteria, or classified as bleeding type 2 (requiring hospitalization or medical intervention), type 3 (overt bleeding requiring at least any blood transfusion or with hemoglobin drop of at least 3 g/l), or type 5 (fatal bleeding) according to the BARC criteria. Hemorrhagic stroke was classified as a bleeding episode. Finally, a combined endpoint of ischemic and bleeding events (stroke, myocardial infarction, major or LTB) was also assessed.
Antithrombotic and bridging strategies
VKA was suspended between 48 h to 5 days pre-TAVR depending on each participating center. During the perioperative interruption of warfarin, 7 centers undertook bridging anticoagulation therapy with low molecular weight heparin, adjusted by creatinine clearance. Five other centers did not perform any anticoagulation bridging. Anticoagulation during the procedure was undertaken with intravenous heparin and the dose was adjusted to obtain an activated clotting time >250 s. Vitamin K antagonists were resumed between 24 and 48 h post-TAVR, and low molecular weight heparin was maintained until the international normalized ratio was ≥2 in those centers in which bridging anticoagulation was undertaken. APT (aspirin 80 to 100 mg daily or clopidogrel 75 mg daily) was started at least the day before TAVR (irrespective of the approach), if prescribed. Only 4 centers prescribed a loading dose of APT (clopidogrel 300 mg or aspirin 325 mg) if patients were not already receiving chronic APT.
Descriptive data are presented as mean ± SD or median (interquartile range), or proportion for individual characteristics referring to the patients’ exposure group. Comparisons between the 2 groups were performed with Student t test or Mann-Whitney U test for continuous variables, and with the 2-sided chi-square or Fisher exact test for categorical data. Incidence rates were also assessed as person-year unit. To explore for associations among antithrombotic groups, effectiveness, and safety outcomes, we used a Kaplan-Meier–based cumulative incidence rate with the log-rank test. In addition, we calculated the hazard ratio (HR) and 95% confidence interval (CI) using a Cox proportional hazards model, with patients being censored at the time of first event (taking into account bleeding events and ischemic events independently) or when an antithrombotic strategy was changed. Other causes for censoring were alterations in antithrombotic therapy and loss of follow-up. The MT group (using VKA alone) was used as the reference group. A multivariate Cox model adjusted by age and imbalances in the baseline characteristics (coronary artery disease [CAD], approach, or antithrombotic bridging strategy) was used for comparing event rates at follow-up between groups. In addition, the variability introduced by the center was modeled as a random effect in the adjusted analysis (random-intercept model). We performed a sensitivity analysis, by excluding patients who had not changed their therapeutic strategy after the first event to assess the effect without a possible bias. The risk of stroke was also analyzed in a separate Cox model in which patients were censured at time of the first event or at 6 months. An additional landmark analysis including only the events occurring after the first 30 days was performed. Finally, analysis comparing MT versus DT and TT were also assessed. SPSS version 21.0 (IBM Corp., Armonk, New York) and R package (version 0.99.467 2009-2015, RStudio, Boston, Massachusetts) were used for statistical analysis.
Table 1 outlines the clinical and procedural characteristics of MT- and MAT-treated patients. Compared with MAT-treated patients (i.e., those treated with VKA plus any APT), MT-treated patients (i.e., those treated with VKA therapy alone) had a lower prevalence of CAD (51.5% vs. 24%; p < 0.01). All other baseline characteristics were similar between the groups. The CHADS2 score did not significantly differ between the groups (3.1 ± 1.1 vs. 3.3 ± 1.2; p = 0.19). MT-treated patients underwent low molecular weight heparin bridging therapy more frequently than their MAT-treated counterparts (85.1% vs. 70.6%; p < 0.01). Overall, most patients (71.0 %) underwent transfemoral TAVR, the approach used most frequently in the MT-treated group. The balloon-expandable Edwards valve (SAPIEN, SAPIEN XT, or SAPIEN 3, Edwards Lifesciences, Irvine, California) was the most commonly used valve overall, followed by the self-expandable CoreValve system (Medtronic, Minneapolis, Minnesota), with no between-group differences in usage rates.
Table 2 outlines procedural and in-hospital outcomes post-TAVR. The incidence of major or LTB was significantly higher in the MAT compared with MT group (14.8% vs. 5.9%; p = 0.02). After excluding bleedings related to major vascular complications (bleeding directly related with the procedure), the incidence of bleeding events tended to remain higher in the MAT compared with MT group (9.7% vs. 4.0%; p = 0.07). The incidence of all-cause death, stroke, myocardial infarction, and other in-hospital endpoints was similarly distributed between both groups. Baseline, procedural and in-hospital outcomes of patients who received DT and TT are presented in Online Tables 1 and 2.
During a median follow-up of 13 months (interquartile range: 3 to 31 months), 123 patients died (17.9% per person-year), 61 due to cardiovascular reasons (8.9% per person-year). Table 3 outlines the crude and adjusted HR of all-cause death, cardiovascular death, and fatal bleeding (BARC type 5). Globally, there were no significant differences in the incidence of all-cause death between the MT and MAT groups (18.5% per person-year vs. 17.8% per person-year; adjusted HR: 0.93; 95% CI: 0.58 to 1.50; p = 0.76) or death for cardiovascular cause (8.1 per person-year vs. 9.1% per person-year; adjusted HR: 1.09; 95% CI: 0.54 to 2.22; p = 0.80). There were 12 (1.8% per person-year) fatal bleeding events, with a similar between-group incidence (p = 0.86).
Ninety-nine of 564 patients (14.4% per person-year) presented with a major adverse cardiovascular event (stroke, myocardial infarction, or cardiovascular death) during the follow-up period. Unadjusted analysis demonstrated no significant between-group differences in the incidence of stroke (4.1% per person-year in MT group compared with 4.8% per person-year in MAT; p = 0.88), but a higher incidence of myocardial infarction in the MAT group. These data did not change following a Cox-adjusted analysis, showing no differences between either antithrombotic strategy for the cumulative HR of stroke, nor for the major cardiovascular endpoint (Table 3, Figure 1A). A sensitivity analysis censoring all patients at 6-month follow-up also demonstrated no between-group differences in the incidence of stroke (4% in MT group compared with 3.8% in MAT group; adjusted HR: 1.09; 95% CI: 0.37 to 3.25; p = 0.88).
Bleeding events occurred in 145 (21.1% per person-year) patients, 15 patients (12.1% per person-year) in MT group compared with 130 patients (23.1% per person-year) in the MAT (adjusted HR: 1.73; 95% CI: 1.00 to 3.05; p = 0.05). The incidence of intracranial bleeding was low (global incidence of 1.3% per person-year), with no significant between-group differences (p = 0.30). The unadjusted and adjusted HR for any type of bleeding, including VARC-2 major or LTB, or bleeding requiring transfusion, demonstrate results favoring MT (Table 3, Figure 1B). Access site related was the most frequent cause of bleeding (36.5%) followed by gastrointestinal bleeding (27.6%), intracranial bleeding (6.2%), respiratory tract bleeding (3.5%), urogenital bleeding (2.8%), nose bleeding (2.1%), pericardial bleeding (1.4%), and other or nonspecified bleeding (20.0%). There were no differences in the type of bleeding across therapy groups.
The combined endpoint of stroke, myocardial infarction, or any type of bleeding was reported in 20 (16.1% per person-year) patients in the MT group compared with 155 (27.6% per person-year) in the MAT group (Table 3, Figure 1C).
Antithrombotic strategy remained unchanged after the first event in 48 patients. The sensitivity analysis by excluding this population showed no important variations in the global effect, suggesting a lack of a significant bias by including these patients in the main analysis (Online Table 3).
A landmark analysis including only the events occurring after the first 30 days post-TAVR is shown in Online Figure 1.
Monotherapy versus double therapy
Eighty-nine patients receiving DT (VKA plus only 1 APT agent) died (17.3% per person-year), 47 patients due to CV reasons (9.1% per person-year), 23 patients presented with stroke (4.5% per person-year) and 120 patients presented with any type of bleeding (23.3% per person-year). The analysis demonstrated no between-group differences in the risk of all-cause of death, cardiovascular death, stroke, or the major cardiovascular endpoint (the combined endpoint of stroke, myocardial infarction, or cardiovascular death) between MT versus DT groups (Table 4). The crude and adjusted HR of any type of bleeding including VARC-2 major or LTB, or bleeding requiring transfusion, were greater in the DT group compared with the MT group (Table 4, Figure 2). A further subanalysis including only patients receiving DT demonstrated a higher risk of major or LTB in the subgroup of patients receiving warfarin plus aspirin compared with those patients receiving warfarin plus clopidogrel (adjusted HR 2.86; 95% CI: 1.58 to 5.18; p = 0.0004) (Figure 3).
Exploratory analysis in patients receiving triple therapy
Eleven patients receiving TT (dual APT plus VKA) group died (24.6% per person-year), 4 patients presented with stroke (8.9% per person-year) and 10 patients (19.8% per person-year) presented with any type of bleeding. The HR of stroke and the adjusted HR of major adverse cardiovascular events (stroke, myocardial infarction, or cardiovascular death), and death were similar to those treated with MT (Table 5). Those receiving TT presented with a similar bleeding risk compared with those treated with DT (DT as the reference group; adjusted HR: 0.70; 95% CI: 0.36 to 1.36; p = 0.29), and nonsignificantly higher risk of major or LTB bleeding compared with the MT group (MT as the reference group; adjusted HR: 1.69; 95% CI: 0.63 to 4.54; p = 0.30) (Table 5, Figure 4).
TAVR-related antithrombotic regimens proposed in current societal guidelines are heterogeneous and somewhat empirically based (2,10–12) (Table 6). Expert consensus has thus far been drawn from anecdotal clinical experience, extrapolation from the surgical aortic valve replacement data, and certain parallels gleaned from percutaneous coronary intervention (13). This reflects a current lack of large-scale prospective clinical trials evaluating differing antithrombotic regimens post-TAVR. Managing concomitant AF in TAVR recipients represents an added therapeutic challenge. To the best of our knowledge, the present analysis is the first large-scale study evaluating the effects of differing antithrombotic strategies in AF patients post-TAVR on the occurrence of both thrombotic and bleeding-related events in a multicenter real-world TAVR cohort. The strategy of adding an antiplatelet agent to VKA post-TAVR (MAT) was compared with a more conservative VKA alone (MT) strategy. Additional analyses were performed to evaluate outcomes in those patients receiving only 1 APT agent plus VKA (DT), and an exploratory analysis in those patients receiving 2 APT agents plus VKA (TT). Despite similar stroke or death rates in the MT compared with DT groups, a DT strategy in such patients associated with nearly double the bleeding risk, whereby patients receiving aspirin plus VKA therapy represented the subgroup posing the highest bleeding risk. These findings suggest that prescribing an antiplatelet agent to AF patients already anticoagulated post-TAVR is unlikely to confer added clinical benefit while potentially being harmful.
The optimal antithrombotic strategy post-TAVR in those patients with concomitant AF remains unknown. Most patients in the present analysis harbored a strong indication for anticoagulation, with a mean CHADS2 score of 3. Current guidelines recommend adding an antiplatelet agent to VKA for at least the first 6 months post-TAVR (2). This recommendation arises from the known stroke risk post-TAVR, being especially high within the first 2 weeks post-procedure (14). However, there is little evidence supporting this recommendation, particularly in comparison with simply continuing VKA therapy alone. Stroke appears in the following 2 different scenarios in patients undergoing TAVR: during the periprocedural phase, and during the chronic post-TAVR phase, in line with the stroke incidence of similarly matched non-TAVR patients. Of the periprocedural phase strokes, 50% appear within the first 24 h post-TAVR, probably related to catheter and valve manipulation within an atherosclerotic aorta and diseased aortic valve. Additionally, thromboembolism caused by chronic or new AF, or originating directly from the native transcatheter heart valve complex per se, likely further contributes to strokes >24 h post-TAVR (14). Hence, the argument in favor of a DT strategy (VKA plus single APT) in patients with AF might be to stabilize a damaged aortic wall, and to minimize the risk of thromboembolic episodes during the peri-TAVR period during when international normalized ratio levels are fluctuant or subtherapeutic, and to further confer added protection until endothelialization of the new prosthesis occurs (15,16). However, our data seem not to support the hypothetical superiority of a DT strategy against a VKA alone strategy. In contrast, most of the TAVR recipients harbor high-risk baseline characteristics, such as advanced age, frailty, and renal failure, which in turn simultaneously pose as significant risk factors for bleeding (5). Current guidelines do not recommend adding 2 APT agents to VKA post-TAVR. In our study, <10% of the patients followed this strategy, and more than 75% of them harbored an extra indication of APT (i.e., CAD). The interpretation of the results of the patients receiving TT in our study should be made with caution due to the small sample size of this group and the higher vascular profile risk of these patients compared with MT or DT patients.
In surgical aortic valve replacement recipients, thromboembolic risk is increased following aortic bioprosthetic implantation during the early post-surgical period (17). In patients in sinus rhythm, antithrombotic therapy (aspirin or warfarin) is recommended for at least 3 months until valve endothelialization occurs (10,11). However, there are no specific studies examining the effect of adding 1 antiplatelet agent to VKA in surgical aortic valve replacement patients with concomitant AF. Data evaluating this strategy arise from subanalyses of studies composed of mixed populations (mechanical and biological prosthesis, in aortic and mitral positions) (18), where the possibility of bias was high. In 1 large retrospective registry, the effect of aspirin alone was associated with an increase in thromboembolic events when compared with warfarin alone or DT (aspirin plus warfarin) (19). However, in this study there were no direct comparisons between MT with warfarin alone versus DT. Currently, adding an antiplatelet agent to VKA in patients with an aortic bioprosthetic valve is not recommended in the absence of other indications for APT, such as concomitant CAD. The currently ongoing POPular-TAVI (Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation) trial (NCT02247128) comparing warfarin MT versus DT (warfarin plus single APT) in AF patients undergoing TAVR will provide more definitive data.
Data from AF studies failed to show any beneficial effect for ischemic stroke prevention using a DT strategy (aspirin plus VKA) versus a VKA alone strategy, whereas more frequent bleeding were evident in all studies using DT (4,20). In a meta-analysis comprising more than 4,000 patients from 10 randomized clinical trials, the risk of thromboembolism or mortality was similar with both strategies (20).
In the setting of AF with a clinical indication for additional APT, published evidence and clinical recommendations remain controversial. A recent prospective study performed in 8,700 patients with AF and stable coronary disease (defined as more than 1 year without acute coronary syndrome) suggested that the addition of APT to VKA is not needed in patients who were orally anticoagulated (21). The addition of APT to VKA was not associated with the reduction of recurrent coronary events or stroke compared with VKA therapy alone, yet increased the risk of bleeding events. In contrast, concomitant APT is recommended in patients with unstable CAD or following coronary stenting (13,22). These discrepancies between studies highlight the fact that CAD represents a wide spectrum of patients, and the need for antithrombotic therapies differs in patients with acute coronary syndromes than in patients with stable coronary disease or post-stenting. Needless to say, the rationale of adding APT to VKA in this subgroup of patients is to minimize recurrent coronary events, rather than stroke. Despite the limitations of performing a subanalysis from an observational study, our results suggest that patients receiving DT and concomitant aspirin harbored the highest risk of bleeding, whereas patients receiving clopidogrel presented with a similar bleeding risk than patients receiving MT. These results suggest that adding clopidogrel to VKA in those patients with a mandatory indication for APT (i.e., recent stenting) could represent a relatively safer strategy in those patients already anticoagulated undergoing TAVR.
The number of study participants was relatively low, especially within the TT group. However, the observational nature of our study provided us the opportunity of investigating antithrombotic strategies used in a real-world TAVR setting. Confounding by indication could be present, and patients receiving any APT could present higher vascular risk profile than patients under VKA MT. For this reason, the extrapolation of the results of our study in patients with concomitant CAD should be made with caution despite the statistical adjustments performed. However, the adjusted and unadjusted analyses presented consistent results, and we had sufficient power to control for imbalances in baseline characteristics. Furthermore, the fact that the results presented are also consistent with those observed in non-TAVR populations perhaps strengthens its validity. Finally, the high number of patients censored within the first year, mostly due to a high incidence of events or changes in antithrombotic treatment, could limit the interpretation of the analysis in patients with long survival times. However, considering these aforementioned limitations, the present analysis nevertheless serves as the first data in the TAVR field addressing this important clinical question.
Adding an antiplatelet agent to a VKA in patients with AF undergoing TAVR does not seem to be superior to VKA therapy alone in terms of stroke prevention, while posing a significantly greater bleeding risk. Further prospective randomized studies are required for identifying the optimal antithrombotic strategy in TAVR patients with AF.
WHAT IS KNOWN? There is currently no data on the efficacy and safety of adding an antiplatelet agent in patients with AF undergoing TAVR in the setting of concomitant oral anticoagulation.
WHAT IS NEW? Concomitant use of APT appears not to reduce the incidence of stroke, major adverse cardiovascular events, or death, while simultaneously increasing the risk of bleeding in TAVR recipients prescribed VKA therapy for AF.
WHAT IS NEXT? Randomized trials comparing various combinations of antithrombotic therapies in this clinical setting are warranted to confirm these findings.
Omar Abdul-Jawad Altisent is a PhD student of Universitat Autònoma de Barcelona, Barcelona, Spain. Omar Abdul-Jawad Altisent, Ander Regueiro, and Maria del Trigo were supported by a grant from the Fundación Alfonso Martin Escudero (Madrid, Spain).
For an expanded Results section as well as supplemental figure and tables, please see the online version of this article.
Drs. Abdul-Jawad Altisent, Del Trigo, and Regueiro were supported by a research PhD grant from the Alfonso Martin Escudero Foundation (Madrid, Spain). Dr. Eltchaninoff has received lecture fees from Edwards Lifesciences. Dr. Dager has served as a proctor for the Medtronic CoreValve. Dr. Rodés-Cabau has received research grant support from Edwards Lifesciences, Medtronic, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- atrial fibrillation
- antiplatelet therapy
- Bleeding Academic Research Consortium
- coronary artery disease
- confidence interval
- double therapy
- hazard ratio
- life-threatening bleeding
- multiple antithrombotic therapy
- transcatheter aortic valve replacement
- triple therapy
- Valve Academic Research Consortium-2
- vitamin K antagonist
- Received March 7, 2016.
- Revision received June 10, 2016.
- Accepted June 19, 2016.
- American College of Cardiology Foundation
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