Evidence for the use of Rivaroxaban following an EKOS procedure for PE
Contents
1. Introduction
1.1 Therapeutic problem ..
2. Literature Search
3. Guidelines
4. Critical evaluation of the literature
4.1 Appraisal of Paper 1 Kelley
et al
17
4.2 Appraisal of Paper 2 Schreinlechner
et al
18
5. Discussion
6. Recommendation
7. References
Pulmonary embolism (PE) is a condition caused by a blocked blood vessel occluding blood flow into the lungs. It usually occurs when a blood clot formed in a blood vessel elsewhere moves and obstructs the pulmonary arterial system. This obstruction is known as an emboli, resulting in a severe respiratory dysfunction since the lung area affected is no longer perfused.
1,2
The therapy choice will depend on several factors; the severity of the condition, contraindication to a particular treatment, the presence of comorbidities, the licenced indication of the drug and patients preference.
1
Specialists will usually make clinical decisions on the treatment choice (
Figure 1
) and the duration of treatment.
1
Pharmacological treatment is preferred in haemodynamically stable patients. If the patient is not haemodynamically stable, mechanical interventions such as thrombectomy might be required.
3
In the past years, novel endovascular procedures have emerged to revolutionise thrombosis treatment. Some of these non-surgical procedures use a combination of pharmacological and mechanical treatment with a catheter-directed thrombolysis.
4
Figure 1:
Summary of Pulmonary Embolism treatment options.
Platelets are activated when a blood vessel wall is broken and they start to aggregate in the injured area. The activated platelets trigger the initiation of the clotting cascade to stop the bleeding. Fibrinogen, a soluble plasma protein, will become fibrin as final result of this cascade.
5
Fibrin is an insoluble
protein
displayed in long fibrous chains that entangle more platelets and other blood cells.
6
This builds up a mesh that gradually hardens forming a blood clot.
Fibrin interfere the flow of thrombolytic drugs to the blood clot core, requiring higher doses to be effective. The acoustic pulse field created by ultrasound waves weakens fibrin formation unravelling the mesh blood clot. This technique allows more thrombolytic agent to reach effectively the entire clot.
7
It aims to reduce treatment time and the dose of thrombolytic agent required in catheter-directed thrombolysis (CDT) alone.
3
These techniques use an ultrasound enhanced catheter directed thrombolysis (UE-CDT) also known as ultrasound-assisted catheter-directed thrombolysis (USAT). One of these devices is branded as EkoSonic
Endovascular system (EKOS
), which gives name to this procedure. EKOS
uses high frequency, low energy ultrasonic waves in a catheter that contains a thrombolytic agent infusion to target a specific area (
Figure 2
)
7
. This combination of ultrasound waves and a catheter-directed thrombolysis therapy is currently used to dissolve blood clots for the treatment of PE, Deep Vein Thrombosis (DVT) and Peripheral Arterial Occlusions.
8
Figure 2:
Ekosonic Ultrasonic Endovascular Thrombolysis system
9
.
1.1 Therapeutic problem
The cardiology team within the Trust have been prescribing Rivaroxaban PE treatment dose following an EKOS procedure. Rivaroxaban is an oral anticoagulant licensed in the UK for the treatment of PE and is not licensed for patients with PE who have had an intervention such as EKOS
10
. Thrombolysis is associated with a risk of haemorrhagic complications including stroke. This risk could potentially increase in patients who receive antithrombotic treatment following a thrombolysis therapy intervention.
The aim of this therapeutic review is to appraise the available evidence in order to assess the safety and appropriateness of Rivaroxaban following an EKOS procedure. This will allow for an informed recommendation to be made as to whether the cardiology team should continue to prescribe it under these circumstances.
2. Literature Search
A search was conducted using tertiary sources (Micromedex, UpToDate, DynaMed Plus, Martindale) to gain an overview of the therapeutic area. An extensive literature research was undertaken on Cochrane Library, EMBASE, and Medline databases via NHS Evidences Healthcare Databases Advanced Search (HDAS) to identify relevant papers (Tables 1-4). After completion of the literature search as per Figure 3, three papers were identified for critical analysis (Table 5). The MeSH browser and EMTREE were used to match the search terms on Medline and Cochrane (Table 6).
Due to the small number of hits on these databases, it was not necessary to apply limitations to the search, such as date or language restriction. The full text of the remaining studies were then assessed using the inclusion criteria (Table 7).
Table 1:
EMBASE search (conducted on 16/06/2019)
|
Search |
Search term |
Results |
|
1 |
RIVAROXABAN/ | 14,993 |
|
2 |
LUNG EMBOLISM/ | 85,593 |
|
3 |
INTRAVASCULAR ULTRASOUND/ | 14,447 |
|
4 |
BLOOD CLOT LYSIS/ | 38,207 |
|
5 |
(2 AND 3 AND 4) | 20 |
|
6 |
(3 AND 4) | 282 |
|
7 |
(EkoSonic).af | 153 |
|
8 |
(ekos).af | 371 |
|
9 |
(ultrasound-assisted catheter-directed thrombolysis).af | 80 |
|
10 |
(ultrasound enhanced catheter directed thrombolysis).af | 8 |
|
11 |
(acoustic pulse thrombolysis).af | 13 |
|
12 |
(3 OR 8 OR 9 OR 10 OR 11 OR 12) | 15,027 |
|
13 |
(5 OR 6 OR 12) | 15,027 |
|
14 |
(1 AND 13) | 55 |
Table 2:
MEDLINE search (conducted on 16/6/2019)
|
Search |
Search term |
Results |
|
1 |
RIVAROXABAN/ | 2,624 |
|
2 |
PULMONARY EMBOLISM/ | 37,263 |
|
3 |
ULTRASONICS THERAPY/ | 9,297 |
|
4 |
THROMBOLYTIC THERAPY/ | 22,698 |
|
5 |
(2 AND 3 AND 4) | 24 |
|
6 |
(3 AND 4) | 239 |
|
7 |
(ekosonic).af | 34 |
|
8 |
(ekos).af | 79 |
|
9 |
(ultrasound-assisted catheter-directed thrombolysis).af | 72 |
|
10 |
(ultrasound enhanced catheter directed thrombolysis).af | 22 |
|
11 |
(acoustic pulse thrombolysis).af | 22 |
|
12 |
(7 OR 8 OR 9 OR 10 OR 11) | 179 |
|
13 |
(5 OR 6 OR 12) | 392 |
|
14 |
(1 AND 13) | 1 |
Table 3:
Cochrane Library search (conducted on 16/06/2019)
|
Search |
Search term |
Results |
|
1 |
MeSH descriptor: [Rivaroxaban] this term only | 371 |
|
2 |
MeSH descriptor: [Pulmonary Embolism] this term only | 927 |
|
3 |
MeSH descriptor: [Ultrasonic therapy] this term only | 865 |
|
4 |
MeSH descriptor: [Thrombolytic therapy] this term only | 1653 |
|
5 |
(2 AND 3 AND 4) | 0 |
|
6 |
(3 AND 4) | 0 |
|
7 |
(EkoSonic).af | 4 |
|
8 |
(ekos).af | 18 |
|
9 |
(ultrasound-assisted catheter-directed thrombolysis).af | 14 |
|
10 |
(ultrasound enhanced catheter directed thrombolysis).af | 1 |
|
11 |
(acoustic pulse thrombolysis).af | 6 |
|
12 |
#1 AND (#3 OR #7 OR #8 OR #9 OR #10 OR #11) | 0 |
Table 4:
Key for search strategy with definitions
|
Command |
Definition |
|
/ |
Indicates the Search term is mapped to thesaurus |
|
AND |
Boolean Logic- requires both search terms to be in each result. This narrows the search. |
|
OR |
Boolean Logic requires at least one of terms to be in each result. This broads the search. |
|
af. |
Stands as any field used for free-text searches when the term is not recognised by thesaurus |
Figure 3.
Literature search strategy using EMBASE, Medline and Cochrane Library.
Table 6:
