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Ischemic And Bleeding Risk Assessment After TAVR

Recruiting
Conditions
Aortic Valve Stenosis
Transcatheter Aortic Valve Replacement
Interventions
Other: Low vs Intermediate vs High surgical risk stratified according with SAPT/DAPT/OAC and OAC+SAPT
Registration Number
NCT06000943
Lead Sponsor
Niguarda Hospital
Brief Summary

Transcatheter aortic valve replacement (TAVR) represents an effective treatment to improve symptoms and prognosis in patients with symptomatic severe aortic stenosis (AS) (1-2).

Giving an established uniform approach towards anticoagulation and antithrombotic therapy after TAVR in the post POPULAR-TAVI era, recent data coming from the analysis of different trials, highlight the relevance of the patient's background on the occurrence of ischemic and bleeding events.

Despite this a targeted antithrombotic strategy remains unexplored and all patients undergoing TAVR without other indication to DAPT or OAC, were currently treated according with the concept of "less is more" (only SAPT or only OAC) regardless the risk level (5-6).

The keys points of the project will be 1) the assessment of ischemic and bleeding risk after TAVR stratified according with antithrombotic therapy and surgical risk; 2) the evaluation of the impact of prostheses type and the complete blood count variables (hemoglobine and platelets) on the daily average ischemic and bleeding risk and 3) the evaluation of the dynamic therapeutic changes after TAVR during the follow up.

Detailed Description

Nowadays in the post POPULAR-TAVI era, after transcatheter aortic valve replacement (TAVR), an establish uniform approach towards anticoagulation and antithrombotic therapy were established.

All patients undergoing TAVR without other indication to dual antiplatelet therapy (DAPT) or oral anticoagulation (OAC), were currently treated according with the general concept of "less is more" (only single antiplatelet therapy - SAPT or only oral anticoagulation - OAC) \[1-3\].

By comparing the frequency of ischemic and bleeding events, data from trial revealed that the bleeding events were more frequent than the ischemic one despite the level of surgical risk, however a gradient of reduction in terms of difference was seen from the highest to the lowest risk profile \[4\].

Furthermore, recent literature showed how the timeframe analysis approach, giving the possibility for a complete time variability evaluation, is able to visualize the fluctuation of the risk over the time. Unfortunately, no stratified data according with the surgical risk level, are available using this approach \[5\].

Moreover, despite these results that highlight the relevance of the patient's background on the occurrence of ischemic and bleeding events, a tailored antithrombotic strategy remains unexplored and all patients undergoing TAVR without other indication to DAPT or OAC, were currently treated with a uniform approach in terms of intensity during the time (1-3).

1.1. Assessment of ischemic and bleeding risk after TAVR according with antithrombotic therapy and surgical risk The rate of adverse thrombotic and hemorrhagic events occurred in the first days after the procedure, were mainly driven by the TAVR's access bleeding and the periprocedural stroke.

Recent study, using the average daily risk analysis, showed the prevalence of the ischemic risk in the first 30 days after the procedure followed by a rising of the bleeding one which become predominant during the follow up, affecting the long-term prognosis \[5\].

However, only data based on surgical risk derived from the 'first time event approach' are available in the literature and none of them investigates whether the higher expected risks - both ischemic and hemorrhagic - in the highest risk cohort remain high even months after TAVR.

Bearing this in mind, these observations revealed that ischemic and bleeding events are not evenly distributed over time, suggesting that a risk-based modulation of the antithrombotic therapy could be better capture the time-dependent evolution of the phenomena. Experience from several studies on antithrombotic therapy in the PCI field, have focused on the intensity and the timing of administration, while no such evidence exists in the field of TAVR (6-7).

Thus, the comprehension of this phenomena holds the potential benefit of a tailored antithrombotic therapy guided by an integrated approach based on the trend of ischemic and bleeding risk stratified according to the patient's risk profile and the antithrombotic regimen adopted.

1.2. Impact of prostheses type and complete blood count variables on ischemic and bleeding events As the same of patient's features and periprocedural variables, it is possible to assume that also the prostheses characteristics in terms of type of leaflet (porcine vs bovine), stent frame amount (short frame versus long frame) and the number of they (valve-in-valve), are not fully investigated previously and may play a role in the thrombotic and hemorrhagic adverse events occurrence.

Understanding the impact of structural and functional valve's characteristics on the bleeding and ischemic risk among patients who undergo TAVR, may have important implications in prosthesis and antithrombotic therapy selection and needs to be investigated properly with a "repeated-event" analysis.

Moreover, also the frequent phenomenon of anemia and thrombocytopenia after TAVR, were identified from several studies as predictors of poor outcome up to 1 year follow up even with a perfect prosthesis function and despite the mechanism behind, it's not completely understood (8). According to these data the relationship between blood count abnormalities, type of prosthesis and ischemic and bleeding risk have never been explored.

The identification of predictive variables leading to the development of anemia and thrombocytopenia and their impact on the risk of hemorrhagic and thrombotic events, might allow us a tailored selection of prosthesis, antithrombotic strategy and procedural planning in order to potentially reduce the risk of adverse events.

1.3. Dynamic therapeutic changes after TAVI Several studies investigated the impact of different antithrombotic strategies on outcomes and prosthesis performance by comparing different approaches in combination. However, most of them assessed the clinical endpoints considering only the discharge therapy, with a lack of real data in terms of regimes switching and duration of any effective treatment prescribed.

The assessment of these data during follow-up, remains underexplored even though their availability could potentially allow an accurate definition of the ongoing strategy at the time of adverse event occurrence. Moreover, the collection of these variables may provide important information about the antithrombotic management, including the reason, the rate and the timing of crossover for each treatment.

Finally, given the evolution of the antithrombotic strategy in the last years, in particular in the pre and post Popular TAVI era, and knowing the therapeutic management during the first year of follow up, it's possible to define the impact of any study/trial on the real-world approach in recent years.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
2500
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Lower Surgical RiskLow vs Intermediate vs High surgical risk stratified according with SAPT/DAPT/OAC and OAC+SAPTSurgical risk stratification. All the following groups will be define according with STS and Euroscore II score and stratified based on antithrombotic strategy in all possible combinations (SAPT, DAPT, OAC, OAC+SAPT)
Intermediate Surgical RiskLow vs Intermediate vs High surgical risk stratified according with SAPT/DAPT/OAC and OAC+SAPTSurgical risk stratification. All the following groups will be define according with STS and Euroscore II score and stratified based on antithrombotic strategy in all possible combinations (SAPT, DAPT, OAC, OAC+SAPT)
High Surgical RiskLow vs Intermediate vs High surgical risk stratified according with SAPT/DAPT/OAC and OAC+SAPTSurgical risk stratification. All the following groups will be define according with STS and Euroscore II score and stratified based on antithrombotic strategy in all possible combinations (SAPT, DAPT, OAC, OAC+SAPT)
Primary Outcome Measures
NameTimeMethod
Trend of average daily ischemic risk (ADIR) and average daily bleeding risk (ADBR)At 30-days, 90-days and 1 year

ADIR was calculated as the total number of ischemic events (CV deaths, MI, ischemic stroke and other thrombotic events-including repeat events) divided by the number of patients-day at risk.

ADBR was calculated as the total number of bleeding events (including repeat events) divided by the number of the number of patients-day at risk.

Average daily risks (ADRs) in different type of valve prosthesisAt 30-days, 90-days and 1 year

Trend and prevalence of ADIR and ADBR in different type and number of prosthesis (long frame vs short frame, balloon versus self-expandable, porcine vs bovine, Single Valve vs Valve in Valve) and calculated as the total number of events divided by the number of patients-day at risk

Secondary Outcome Measures
NameTimeMethod
Type of antithrombotic regimen changes after TAVRAt 30-days, 90-days and 1 year

Type of changes in antithrombotic strategy taking into account all interclass (antiplatelet to anticoagulant or vice versa) and intraclass drugs switches (anticoagulant - VKA to DOAC, antiplatelet - DAPT to SAPT or vice versa)

Average daily risks (ADRs) in different type of valve prosthesisAt 30-days, 90-days and 1 year

Trend and prevalence of ADIR and ADBR in different type and number of prosthesis (long frame vs short frame, balloon versus self-expandable, porcine vs bovine, Single Valve vs Valve in Valve) and calculated as the total number of events divided by the number of patients-day at risk

Average daily risks (ADRs) in anaemic and thrombocytopenic patientsIn hospital up to 1 year

Trend and prevalence of ADIR and ADBR in patients who developed anaemia and thrombocytopenia after the procedure and during the hospitalization. Anaemia and thrombocytopenia were defined according to the WHO and EHA guidelines. ADRs were calculated as the total number of events divided by the number of patients-day at risk

Rate of antithrombotic regimen changes after TAVRAt 30-days, 90-days and 1 year

Percentage of antithrombotic strategy changes

Timing of antithrombotic regimen changes after TAVRAt 30-days, 90-days and 1 year

Number of days after the procedure in which the antithrombotic strategy was changed

Trial Locations

Locations (12)

Complejo Asistencial Dr. Sótero del Río

🇨🇱

Santiago, Chile

Puerto Real University Hospital, Puerto Real

🇪🇸

Cadiz, Spain

OLV Hospital

🇧🇪

Aalst, Belgium

Cardiocenter, 3rd Medical School, Charles University and University Hospital Kralovske Vinohrady

🇨🇿

Prague, Czechia

Humanitas Research Hospital

🇮🇹

Rozzano, Milano, Italy

ASST GOM Niguarda

🇮🇹

Milano, Italia, Italy

Ospedale Galeazzi Sant'Ambrogio

🇮🇹

Milano, Italy

IRCCS Policlinico San Donato

🇮🇹

San Donato Milanese, Milano, Italy

IRCCS Ospedale Policlinico San Martino

🇮🇹

Genova, Italy

A.O.U. Città della Salute e della Scienza di Torino

🇮🇹

Torino, Italy

San Carlo Hospital

🇮🇹

Potenza, Italy

Azienda Ospedaliera Sant'Andrea

🇮🇹

Roma, Italy

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