Continuation versus Interruption of Oral Anticoagulation during TAVI.

BACKGROUND: One third of patients undergoing transcatheter aortic-valve implantation (TAVI) have an indication for oral anticoagulation owing to concomitant diseases. Interruption of oral anticoagulation during TAVI may decrease the risk of bleeding, whereas continuation may decrease the risk of thromboembolism. METHODS: We conducted an international, open-label, randomized, noninferiority trial involving patients who were receiving oral anticoagulants and were planning to undergo TAVI. Patients were randomly assigned in a 1:1 ratio to periprocedural continuation or interruption of oral anticoagulation. The primary outcome was a composite of death from cardiovascular causes, stroke from any cause, myocardial infarction, major vascular complications, or major bleeding within 30 days after TAVI. RESULTS: A total of 858 patients were included in the modified intention-to-treat population: 431 were assigned to continuation and 427 to interruption of oral anticoagulation. A primary-outcome event occurred in 71 patients (16.5%) in the continuation group and in 63 (14.8%) in the interruption group (risk difference, 1.7 percentage points; 95% confidence interval [CI], -3.1 to 6.6; P = 0.18 for noninferiority). Thromboembolic events occurred in 38 patients (8.8%) in the continuation group and in 35 (8.2%) in the interruption group (risk difference, 0.6 percentage points; 95% CI, -3.1 to 4.4). Bleeding occurred in 134 patients (31.1%) in the continuation group and in 91 (21.3%) in the interruption group (risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6). CONCLUSIONS: In patients undergoing TAVI with a concomitant indication for oral anticoagulation, periprocedural continuation was not noninferior to interruption of oral anticoagulation during TAVI with respect to the incidence of a composite of death from cardiovascular causes, stroke, myocardial infarction, major vascular complications, or major bleeding at 30 days. (Funded by the Netherlands Organization for Health Research and Development and the St. Antonius Research Fund; POPular PAUSE TAVI ClinicalTrials.gov number, NCT04437303.).

The impact of stroke and bleeding on mortality and quality of life during the first year after TAVI: A POPular TAVI subanalysis.

BACKGROUND: Bleeding and stroke are frequent complications after transcatheter aortic valve implantation (TAVI). The mortality risk associated with these events has been reported before, but data regarding their impact on health-related quality of life (QoL) is limited. AIM: To evaluate the impact of bleeding and stroke occurring within 30 days after TAVI, on mortality and QoL during the first year after TAVI. METHODS: POPular TAVI was a randomized clinical trial that evaluated the addition of clopidogrel to aspirin or oral anticoagulation in patients undergoing TAVI. Besides clinical outcomes, QoL was assessed using the Short Form-12 and EuroQoL Five Dimensions questionnaires before, and at 3, 6, and 12 months after TAVI. RESULTS: Major or life-threatening bleeding occurred in 81 patients (8.3%) and was associated with an increased risk of death (hazard ratio [HR] 1.95 [95% confidence interval (CI) 1.00-3.79]); minor bleeding occurred in 104 patients (10.6%) and was not associated with mortality (HR 0.75 [95% CI 0.30-1.89]). Stroke occurred in 35 patients (3.6%) and was associated with an increased risk of death (HR 2.90 [95% CI 1.23-6.83]). Mean mental component summary (MCS-12) scores over time were lower in patients with major or life-threatening bleeding (p = 0.01), and similar in patients with minor bleeding, compared to patients without bleeding; mean physical component summary (PCS-12) scores, EQ-5D index, and visual analog scale (VAS) were similar between those patients. Mean MCS-12 scores were lower in patients with stroke (p = 0.01), mean PCS-12, EQ-5D index, and VAS were similar compared to patients without stroke. CONCLUSION: Major or life-threatening bleeding and stroke were associated with an increased risk of death and decreased mental QoL in the first year after TAVI.

Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

BACKGROUND: The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied. METHODS: We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P = 0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P = 0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31). CONCLUSIONS: In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

BACKGROUND: The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS: In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P = 0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P = 0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, -8.2 percentage points; 95% CI for noninferiority, -14.9 to -1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P = 0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, -0.2 percentage points; 95% CI for noninferiority, -4.7 to 4.3; P = 0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P = 0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS: Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

The effect of transcatheter aortic valve implantation approaches on mortality.

OBJECTIVES: We aimed to evaluate the effect of transcatheter aortic valve implantation (TAVI) approaches on mortality and identify effect modifiers and predictors for mortality. BACKGROUND: Alternative access routes to transfemoral (TF) TAVI include the surgical intra-thoracic direct-aortic (DA) and transapical (TA) approach. TA TAVI has been associated with a higher mortality rate. We hypothesized that this is related to effect modifiers, in particular the left ventricular ejection fraction (LVEF). METHODS: This multicentre study derived its data from prospective registries. To adjust for confounders, we used propensity-score based, stabilized inverse probability weighted Cox regression models. RESULTS: In total, 5,910 patients underwent TAVI via TF (N = 4,072), DA (N = 524), and TA (N = 1,314) access. Compared to TF, 30-day mortality was increased among DA (HR 1.87, 95%CI 1.26-2.78, p = .002) and TA (HR 3.34, 95%CI 2.28-4.89, p < .001) cases. Compared to TF, 5-year mortality was increased among TA cases (HR 1.50, 95%CI 1.24-1.83, p < .001). None of the variables showed a significant interaction between the approaches and mortality. An impaired LVEF (≤35%) increased mortality in all approaches. CONCLUSIONS: The surgical intra-thoracic TA and DA TAVI are both associated with a higher 30-day mortality than TF TAVI. TA TAVI is associated with a higher 5-year mortality than TF TAVI. The DA approach may therefore have some advantages over the TA approach when TF access is not feasible.

Can TAVR Be Effectively and Safely Performed Without Intraprocedural TEE?

PURPOSE OF REVIEW: The TAVR procedure is a well-established therapy for patients with severe aortic stenosis at intermediate/high risk for surgery and a potential treatment for low-risk patients. It is much less invasive with short hospital stays and presents similar results compared with SAVR. Different "minimalist approach strategies" were proposed in order to obtain this performance. In these settings, transesophageal echocardiography (TEE) became less relevant for the TAVR procedure. The present review provides an update regarding the safety of TAVR without intraprocedural TEE. RECENT FINDINGS: Transthoracic echocardiography and fluoroscopy are the primary imaging tools during TAVR. Several studies proved that TAVR under local anesthesia without TEE is as safe as that performed under TEE guidance. However, not all patients have a proper window for TTE, and particular cases with complex anatomy can benefit from TEE support during the intervention. Intraprocedural TEE no longer plays a crucial role in the TAVR procedure, but in some instances, it remains of great help to detect and avoid complications.

Insight on patient specific computer modeling of transcatheter aortic valve implantation in patients with bicuspid aortic valve disease.

OBJECTIVE: The aim of this study was to describe the early use of dedicated patient specific computer modeling in patients with bicuspid aortic valve (BAV) undergoing transcatheter aortic valve implantation (TAVI), in predicting procedure feasibility and patient related outcome. BACKGROUND: Dedicated patient specific computer modeling, used for optimizing TAVI procedures, is currently validated for the prediction of contact pressure, valve morphology and paravalvular leakage (PVL). The simulation of TAVI procedures is increasingly used in patients with tricuspid aortic valve stenosis. Currently, BAV disease is considered as a relative contra-indication for TAVI due to its specific anatomical characteristics. METHODS: This single center study consisted of seven patients with BAV undergoing TAVI. A patient specific computer simulation was performed based on multislice computer tomography images. The model advised the best fitting prosthetic valve size or sizes and simulated this valve on different implantation depths with the corresponding presence and severity of PVL and prosthetic valve morphology. The simulation results were compared with the procedural outcomes using transesophageal echocardiography (TEE) and fluoroscopy. RESULTS: The patient specific computer modeling predicted accurately the outcome (PVL and valve morphology) of TAVI in all cases. In one case, the TAVI procedure was unsuccessful and retrospectively not suitable for TAVI, which was correctly predicted by the model. CONCLUSION: The patient specific computer modeling adequately predicts feasibility and outcome of TAVI in patients with BAV disease and may extend the applicability of TAVI. Moreover, it improves decision-making and therefore individual procedural outcomes in this difficult patient population.

Sex Differences in Outcomes After Transcatheter Aortic Valve Replacement: A POPular TAVI Subanalysis.

BACKGROUND: Stroke and bleeding are complications after transcatheter aortic valve replacement (TAVR). A higher incidence of bleeding and stroke has been reported in women, but the role of antithrombotic management pre- and post-TAVR has not been studied. OBJECTIVES: The study sought to compare bleeding and ischemic complications after TAVR between women and men stratified by antiplatelet and oral anticoagulant (OAC) regimen. METHODS: The POPular TAVI (Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation) trial was a randomized clinical trial to test the hypothesis that monotherapy with aspirin or OAC after TAVR is safer than the addition of clopidogrel. The primary endpoints of interest of this post hoc subanalysis were: 1) all bleeding; and 2) a composite of ischemic events consisting of stroke and myocardial infarction. Secondary endpoints were: 1) nonprocedural bleeding; 2) major or life-threatening bleeding; 3) minor bleeding; 4) stroke; 5) myocardial infarction; and 6) all-cause death. RESULTS: A total of 978 patients (466 [47.6%] women) were included in this study. All bleeding and the composite of myocardial infarction and stroke rates were similar between sexes (all bleeding: 106 [22.8%] women vs 121 [23.6%] men; P = 0.815; ischemic events: 26 [5.6%] vs 36 [7.0%]; P = 0.429). However, major or life-threatening bleeding occurred more often in women (58 [12.5%]) vs men (38 [7.4%]) (P = 0.011), most of which were access site bleedings. The use of aspirin pre- and post-TAVR increased major or life-threatening bleeding in women but not in men. CONCLUSIONS: After TAVR, overall bleeding and ischemic outcomes were similar between women and men. However, women had more major or life-threatening bleedings, especially those receiving aspirin pre- and post-TAVR.

Periprocedural continuation versus interruption of oral anticoagulant drugs during transcatheter aortic valve implantation: rationale and design of the POPular PAUSE TAVI trial.

About one-third of patients undergoing transcatheter aortic valve implantation (TAVI) use oral anticoagulants (OAC), mainly due to atrial fibrillation. General guidelines advise interrupting OAC in patients with a high risk of bleeding undergoing interventions. However, preliminary observational data suggest that the continuation of OAC during TAVI is safe and may reduce the risk of periprocedural thromboembolic events. The Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI) is a multicentre, randomised clinical trial with open-label treatment and blinded endpoint assessment. Patients are randomised 1:1 to periprocedural continuation versus interruption of OAC and are stratified for vitamin K antagonist or direct oral anticoagulant use. The primary endpoint is a composite of cardiovascular mortality, all stroke, myocardial infarction, major vascular complications and type 2-4 bleeding within 30 days after TAVI, according to the Valve Academic Research Consortium-3 criteria. Secondary endpoints include separate individual and composite outcomes, quality of life and cost-effectiveness. Since continuation of OAC is associated with the ancillary benefit that it simplifies periprocedural management, the primary outcome is first analysed for non-inferiority; if non-inferiority is proven, superiority will be tested. Recruitment started in November 2020, and the trial will continue until a total of 858 patients have been included and followed for 90 days. In summary, POPular PAUSE TAVI is the first randomised clinical trial to assess the safety and efficacy of periprocedural continuation versus interruption of OAC in patients undergoing TAVI.