WO2023054762A1 - Method for treating coronary in-stent restenosis having occurred after insertion of bioresorbable vascular scaffold and drug-eluting stent - Google Patents

Abstract

The present invention relates to a method for treating restenosis of a DES inserted after a BVS, comprising the step of inserting a balloon coated with an intimal hyperplasia inhibitor into the pathological blood vessel of a patient with vascular restenosis after the occurrence of restenosis of a DES inserted after a BVS, and inflating the balloon so that the balloon comes in contact with the intima of the blood vessel.

Description

Treatment of coronary restenosis after implantation of bioresorbable vascular scaffold and drug-eluting stent

The present invention relates to a method for treating coronary artery restenosis (ISR) after implantation of a bioresorbable vascular scaffold (BVS) and a drug-eluting stent (DES). .

Although prognosis has improved with the use of second-generation drug-eluting stents (DES) in percutaneous coronary intervention, intra-stent restenosis (ISR) is an area to be overcome. A bioabsorbable vascular scaffold (BVS) has been developed to overcome the limitations of stent use, such as intra-stent restenosis (ISR) and long-term antithrombotic agent requirements.

Although bioresorbable vascular scaffolds (BVS) have significant advantages with respect to vascular repair, significantly higher rates of scaffold thrombosis have been reported in bioresorbable vascular scaffolds (BVS) than drug-eluting stents (DES), so their use is currently discouraged. stopped If scaffold thrombosis occurs, additional procedures such as drug-eluting stent (DES) implantation are required. There are approximately 2,800 patients in Korea who have used absorbable vascular scaffolds (BVS), and follow-up is required for these patients. .

An object of the present invention is to provide a treatment method for coronary restenosis after implantation of a bioabsorbable vascular scaffold (BVS) and a drug-eluting stent (DES).

1. A drug-eluting balloon (Drug- A treatment method comprising placing an Eluting Balloon (DEB) and expanding the balloon so that the balloon directly contacts the vascular intima for a certain period of time.

2. The treatment method according to 1 above, wherein the intimal proliferation inhibitor is paclitaxel.

3. The method according to 1 above, wherein the expansion of the balloon is performed by inflating the balloon by inflating it by a difference in atmospheric pressure after injecting high-pressure air into the balloon.

The present invention can effectively treat patients with coronary artery restenosis after implantation of a bioresorbable vascular scaffold (BVS) and a drug-eluting stent (DES) using a drug-eluting balloon (DEB).

Figure 1 relates to percutaneous coronary intervention with a diagnosis of unstable angina 36 months ago. A is a coronary angiography image showing severe stenosis in the proximal part of the left anterior descending artery, B is a bioresorbable vascular scaffold at the lesion site. An optical coherence tomography image showing optimal implantation is shown.

Figure 2 relates to scaffold thrombosis that occurred 20 months ago, A is a coronary angiography image showing proximal complete occlusion of the left anterior descending artery, B is an optical coherence tomography image showing a red thrombus associated with scaffold strut collapse, C shows successful revascularization by implantation of a drug-eluting stent (DES) covering the entire segment of the scaffold, and D is an optical coherence tomography image showing optimal implantation of DES on a bioresorbable vascular scaffold. .

Figure 3 relates to restenosis that occurred after BVS and drug-eluting stent implantation. A is a coronary angiography image showing significant stenosis in the proximal portion of the left anterior descending artery, B is a plaque rupture in the process of neointimal proliferation of a drug-eluting stent. and optical coherence tomography image showing part of collapsed scaffold strut, C is coronary angiography image showing optimal endovascular diameter increase after angioplasty with a drug-eluting balloon, D is optimal endovascular diameter area gain It shows an optical coherence tomography image showing .

Hereinafter, the present invention will be described in detail.

In the present invention, after implantation of a bioabsorbable vascular scaffold and a drug-eluting stent, a drug-eluting balloon coated with an intimal proliferation inhibitor is placed on a lesion in which restenosis has occurred in the corresponding blood vessel, and the balloon is expanded so that the balloon is placed on the intimal It relates to a method of treating coronary artery restenosis comprising the step of bringing the patient into direct contact for a certain period of time.

Stenting is a very important procedure used in the treatment of coronary artery diseases such as angina pectoris and acute myocardial infarction. Although these procedures have improved the prognosis of patients with ischemic heart disease, the persistent presence of stents in blood vessels remains a potential cause of acute or chronic complications such as restenosis and stent thrombosis. A bioresorbable vascular scaffold that disappears over time has been proposed, but a significantly higher rate of scaffold thrombosis has been reported in bioresorbable vascular scaffolds (BVS), so their use has now been discontinued.

Restenosis in the stent in the present invention refers to a case in which ischemic heart disease is caused again because the blood vessel does not properly maintain the diameter and area after the procedure, and various causes and clinical factors act. Coronary artery intervention using a drug-eluting stent that elutes an inhibitor of intimal proliferation is considered a standard treatment because intimal proliferation is the main pathological mechanism of restenosis within the stent. Despite these achievements, the risk of restenosis within the stent still exists in some patients.

The present invention relates to a bioabsorbable vascular scaffold and a method for treating restenosis after drug-eluting stent implantation.

In the present invention, the vascular intimal proliferation inhibitor refers to a substance (drug) that inhibits vascular intimal proliferation, and can prevent vascular stenosis caused by vascular intimal proliferation. It may be a type of cell proliferation inhibitor, for example paclitaxel.

The coating concentration may be, for example, 1 mg/mm ² to 5 mg/mm ² , but is not limited thereto.

The balloon is coated with an intimal proliferation inhibitor, which may use an additive such as an excipient for binding the inhibitor to the balloon. For example, urea, polysorbate, sorbitol, butyryl-tri-hexyl citrate (BTHC), citrate ester, and the like may be used.

In the present invention, a balloon coated with an inhibitor of vascular intimal proliferation is a balloon used for dilating blood vessels, and means a medical device in which the drug locally acts on a lesion to inhibit vascular intimal proliferation.

When a balloon coated with an intimal proliferation inhibitor is expanded and the balloon directly contacts the vascular intimal for a certain period of time (eg 60 seconds), the intimal proliferation inhibitor is released to prevent the intimal proliferation and to prevent restenosis of the blood vessel. It can be prevented. This can be done, for example, by injecting air at high pressure into the balloon and then exposing it to atmospheric pressure, allowing it to inflate by a difference in air pressure. The high-pressure condition may be 10 to 20 atm, 12 to 20 atm, 12 to 18 atm, etc., and the predetermined time may be selected from 30 to 60 seconds or longer for clinical situations such as blood vessel diameter and temporary blockage of blood flow.

Processes such as insertion of the balloon coated with the vascular intimal growth inhibitor and subsequent removal may be performed by a method used in conventional angioplasty.

Hereinafter, an embodiment will be described in detail to explain the present invention in detail.

test subject

A 60-year-old man was brought to the emergency room with chest pain. The patient's symptoms occurred during exercise 3 days ago and worsened 1 hour ago, so he visited the emergency room. The patient underwent BVS (3.5mm × 18mm Absorb GT1 everolimus-eluting bioresorbable scaffold, Abbott Vascular, Santa Clara, CA, United States) proximal to the left anterior descending artery (LAD) under diagnosis of unstable angina 36 months ago. (Fig. 1). Twenty months ago, the patient was diagnosed with ST-segment elevation acute myocardial infarction associated with scaffold thrombosis (FIG. 2A). Collapse of scaffold struts and red blood clots were confirmed on OCT (Dragonfly, St. Jude Medical, St. Paul, MN, USA; (Fig. 2b)), and DES (3.5 mm × 33 mm) capable of covering the entire segment of the scaffold. XIENCE everolimuseluting stent, Abbott Vascular, Santa Clara, CA, United States) was used for treatment (Figs. 2c and 2d).

The patient's blood pressure was 130/80 mmHg, heart rate was 66 bpm, respiratory rate was 14 times per minute, body temperature was 36.8 °C, and oxygen saturation in the room air was 98%. The initial electrocardiogram showed an anterior wall Q-wave, and blood tests including cardiac enzymes were normal.

Coronary angiography (CAG) revealed severe stenosis (>90% in diameter) proximal to the LAD, suggesting that restenosis had occurred at the site of prior BVS and DES (Fig. 3a). Plaque rupture and collapsed scaffold struts were observed in the neointimal hyperplasia of DES on OCT (Fig. 3b).

The patient was finally diagnosed with unstable angina caused by restenosis of the DES inserted after BVS.

Experiment method

In this experiment, balloon angioplasty was performed using a 2.5 mm × 20 mm semi-compliant balloon and a 3.0 mm × 12 mm non-compliant balloon to treat restenosis of an implanted DES after BVS. A drug-eluting balloon (DEB) was selected rather than DES, and specifically, a DCB (3.5 mm × 26 mm SeQuent Please paclitaxel-eluting balloon, B. Braun, Melsungen, Germany) was injected under conditions of 16 atm (maximum diameter 4.0 mm, for 60 seconds). , and subsequent coronary angiography confirmed residual stenosis in less than 10%. (Fig. 3c). OCT showed optimal luminal gain (minimum/average luminal diameter; 3.25/3.45 mm, minimal luminal area; 9.45 mm ² , Fig. 3d). The patient was discharged the day after the procedure and was prescribed ticagrelor 90 mg twice daily, aspirin 100 mg, and rosuvastatin 20 mg once daily.

Experimental results and follow-up

In this example, a case of acute coronary syndrome due to restenosis of DES inserted after BVS was observed. The patient was on potent dual antiplatelet therapy (DAPT) and statins for 12 months, and no major cardiovascular events occurred during that time.

Complications such as recurrence of late procedural lesions in patients with coronary artery stenosis undergoing metallic DES may be related to the persistent presence of a metallic stent frame locally in the coronary artery wall. Through recent actual data, it was confirmed that lesion complexity and cardiovascular risk factors are the main factors for the recurrence of BVS surgical lesions. In this case, the late scaffold thrombosis was associated with strut discontinuity and areas of low intensity around the strut. In this case, the patient took continuous and potent dual antiplatelet drugs such as ticagrelor and aspirin, and had DES to cover the entire segment of the scaffold. underwent arterial intervention.

This case highlights the importance of optical coherence tomography (OCT) as an imaging test to identify the specific mechanism of surgical lesion recurrence. If appropriate drug therapy is performed and DCB is used, it is judged to be effective in preventing and treating restenosis after coronary intervention.

Claims (3)

1. A drug-eluting balloon coated with an intimal proliferation inhibitor at the lesion site of the coronary artery in patients with coronary artery restenosis after implantation of a bioresorbable vascular scaffold (BVS) and drug-eluting stent (DES) , DEB), and inflating the balloon so that the balloon is in direct contact with the vessel intima for a certain period of time.
2. The method according to claim 1, wherein the intimal proliferation inhibitor is paclitaxel.
3. The method according to claim 1, wherein the expansion of the balloon is performed by inflating the balloon by inflating it by a difference in atmospheric pressure after injecting high-pressure air into the balloon and then exposed to normal pressure.

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