Optimal pharmacotherapy in patients undergoing structural procedures within the left atrium

Project Team

dr hab. med. Jerzy Pręgowski, prof. Inst

Project Manager/National Coordinator in the study STOP CLOT

dr. hab. med. Radosław Pracoń

Substantive manager and national coordinator in the study SAFE LAAC i SAFE LAAC CKD

prof. dr hab. med. Marcin Demkow

Subject expert in the study SAFE LAAC i SAFE LAAC CKD

mgr Katarzyna Istynowicz

Project administrative manager, CWBK

Project value
Project value
Value of the Funding

Funding::

The project is funded by:
Medical Research Agency

Competition: : ABM/2020/1
Project Number: 2020/ABM/01/00002

Implementation period: 2020-2026 r.

Project Name:

Optimal pharmacotherapy in patients undergoing structural procedures within the left atrium with access through the interatrial septum in the perioperative perspective (STOP CLOT Trial) and medium-term perspective (SAFE LAAC Trial)

Project Description:

With the aging of the Polish population, the demand for cardiological endovascular structural procedures with documented value in extending life and improving its quality is growing. Some of these procedures require puncturing the interatrial septum, manipulation within the left atrium, and leaving artificial material in the left heart chambers. This creates a risk of iatrogenic clot formation and consequently embolic stroke or peripheral embolism. Stroke and peripheral embolism are complications with serious individual, social, and economic consequences. To avoid them, patients undergo pharmacotherapy reducing blood clotting, which, however, increases the risk of serious bleeding also burdening patients’ prognosis and the healthcare system budget.

In this project, patients undergoing procedures with access through the interatrial septum will participate. These are patients with mitral regurgitation treated with the “edge-to-edge” technique (TEER) using the MitraClip or PASCAL system, and patients with atrial fibrillation undergoing left atrial appendage closure (LAAC) procedure. Both populations are burdened with particularly high thrombotic and hemorrhagic risk, and the currently used intra- and postoperative pharmacotherapy protocols are empirical.

This project aims to obtain the first randomized data on optimal intra- and postoperative pharmacotherapy, allowing for standardization of procedures and improvement of patient safety, and thus the health and economic effectiveness of the studied procedures.

The project assumes the implementation of three synchronized protocols: the STOP CLOT, SAFE-LAAC, and SAFE LAAC CKD studies, allowing for better utilization of resources within one budget.

Study titled “Strategy for optimizing intraoperative anticoagulation in structural procedures with access through the interatrial septum”

Acronym: STOP CLOT

The aim of the study is to determine the optimal moment to start intraoperative anticoagulant treatment with heparin. Currently, there is no data from prospective randomized clinical trials on this subject.

A group of 410 patients treated with mitral valve sealing using the “edge-to-edge” method or left atrial appendage closure will be randomized at a 1:1 ratio to early (before puncturing the interatrial septum) or late (after puncturing the interatrial septum) start of heparin treatment. In both groups, the frequency of embolic and hemorrhagic complications will be compared during 30-day observation. The obtained results will allow determining which scheme is more effective and safer concerning the risk of perioperative embolic complications (such as stroke) and hemorrhagic ones.

Study titled “Optimal antiplatelet therapy after transcatheter left atrial appendage closure (SAFE-LAAC). A randomized comparative study of health effectiveness – a pilot study”

Acronym: SAFE LAAC

The left atrial appendage is a pouch in the heart where, in patients with atrial fibrillation, clots can form, being sources of strokes. Transcatheter closure of the left atrial appendage is a relatively new treatment aimed at its elimination from blood circulation, thus reducing stroke risk. It is an alternative for patients who, for various reasons, cannot take oral anticoagulants long-term. The device closing the appendage is a foreign body in the organism and is largely incorporated within about a month after the procedure. However, in 2-5% of patients, clots related to the closure device are observed during routine check-ups, which can also cause strokes. Currently, we do not know how to most effectively support the incorporation process of the device and avoid clot formation on it. Based on previous experiences, antiplatelet therapy is recommended for varying periods after the procedure, but today it is unknown what the optimal scheme of this therapy is. Antiplatelet therapy can protect against clotting on one hand but significantly increases the risk of bleeding on the other. The pilot randomized SAFE LAAC study aims to assess which length of dual antiplatelet therapy is most effective and safest. We will assess how the length of antiplatelet therapy affects the frequency of strokes, bleedings, and the frequency of clot occurrence on the device, the number and size of new ischemic changes in brain MR imaging, and also new cognitive disorders examined by appropriate psychological tests. The study will be conducted in 7 centers in Poland.

Study titled “Optimal antiplatelet therapy after transcatheter left atrial appendage closure – chronic kidney disease (SAFE LAAC CKD). Accompanying comparative study of health effectiveness – pilot”

Acronym: SAFE LAAC CKD

Dialyzed patients due to end-stage chronic kidney failure, with accompanying atrial fibrillation, are a population of particularly high risk of both thromboembolic and hemorrhagic events, which has been excluded from randomized studies regarding transcatheter closure of the appendage, and in registers, they constitute a very small percentage.

Similar to the SAFE LAAC study, within the SAFE LAAC CKD study, a group of 80 patients after appendage closure procedure will be randomized to different antiplatelet therapy schemes, with serial control assessment for the frequency of clinical endpoints, clots on the occluder, new changes in brain MR, and cognitive function changes, with the inclusion criterion being chronic hemodialysis.

High-quality data regarding optimal therapy in the prevention of thromboembolic complications are especially needed in the group of patients with chronic kidney disease. They will also serve to assess the effectiveness and safety of the appendage closure procedure in chronically dialyzed patients.

HCM in some people is characterized by an asymptomatic course. In others, it is associated with progressive diastolic dysfunction of the left ventricle of the heart due to hypertrophy and fibrosis of the myocardium, ultimately resulting in systolic dysfunction and progressive heart failure. Both heart failure with preserved ejection fraction and reduced ejection fraction inevitably lead to impaired physical capacity, often affecting young, professionally, and socially active people. An additional significant problem in patients with hypertrophic cardiomyopathy is rhythm disorders leading to an increased risk of sudden death.

Currently, for patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction qualifying for surgical treatment, there is no treatment to halt the progression of the disease.

The aim of the project is to seek therapeutic solutions for a condition for which standard medicine has not yet offered satisfying solutions.

Empagliflozin is a drug registered for the treatment of diabetes. In studies in patients with type 2 diabetes and high cardiovascular risk, the use of empagliflozin was associated with a significant decrease in mortality and hospitalizations due to heart failure. Similar beneficial effects (decrease in cardiovascular mortality, decrease in the number of hospitalizations due to heart failure) were observed in patients with heart failure with impaired left ventricular systolic function, and the beneficial effects of treatment were not dependent on the presence of diabetes (i.e., beneficial effects were also observed in patients without diabetes).

The study, led by the National Institute of Cardiology, the leading unit in Poland specializing in diagnosing and treating patients with HCM, will be implemented in cooperation with the Medical University of Białystok, and also with foreign partners: Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland in Kuopio, and Department of Cardiology, VU University Medical Center in Amsterdam.

Project schedule:

The study is funded by the state budget from the Medical Research Agency, Poland, Project Number:: 2020/ABM/01/00002

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