CN111714163A - Application of clopidogrel, ticagrelor, cilostazol, tirofiban, common heparin or bivalirudin in preparation of drugs for treating pan-vascular diseases - Google Patents

Abstract

The invention provides an application of clopidogrel, ticagrelor, cilostazol, tirofiban, common heparin or bivalirudin in preparing a medicine for treating a pan-vascular disease and a one-stop operation method for coronary artery interventional therapy and aortic endoluminal repair. The invention has the following advantages: (1) the medicine participates in one-stop treatment of the next two diseases, thereby avoiding the contradiction of antiplatelet treatment in the fractional operation and avoiding the potential risk of the fractional operation; (2) the patient only undergoes one anesthesia and operation process, two diseases are treated, and the psychology is more acceptable; (3) reduce the hospitalization cost and the total hospitalization duration, and reduce the medical resource consumption.

Description

Application of clopidogrel, ticagrelor, cilostazol, tirofiban, common heparin or bivalirudin in preparation of drugs for treating pan-vascular diseases

The technical field is as follows:

the invention belongs to the field of medicine, and particularly provides application of clopidogrel, ticagrelor, cilostazol, tirofiban, common heparin or bivalirudin in preparation of a medicine for treating a pan-vascular disease, and application of the clopidogrel, ticagrelor, cilostazol, tirofiban and common heparin or bivalirudin in the preparation of an aortic endoluminal repair operation and coronary intervention treatment for a patient in sequence.

Background art:

systemic atherosclerosis patients are widespread. With the increasing aging population of our country, the burden of multiple atherosclerotic diseases is becoming more severe, and the concept of "pan-vascular disease" has also been proposed and is of great interest, and these patients require more comprehensive assessment and treatment.

Therefore, the middle-aged and elderly patients with non-emergency aortic aneurysm, aortic ulcer or dissections are advised to screen coronary artery diseases, so that missed diagnosis is avoided and perioperative myocardial infarction risk caused by coronary heart disease is reduced.

Similarly, for patients undergoing coronary intervention, if necessary, further assessment of aortic lesions, such as thoraco-aortic transluminal ulcer and aortic dissection, is required to complete the aortic CTA examination, and sufficient pre-operative examination helps to reduce missed diagnosis and risk of aortic rupture and bleeding.

Traditional fractional surgery: according to the traditional thinking, for patients suffering from coronary heart disease and aortic disease (aortic aneurysm/aortic ulcer or dissection, etc.) needing interventional therapy, the aortic transluminal repair (EVAR) is usually performed in vascular surgery, and coronary artery interventional therapy is performed in cardiology. The two operations are performed independently.

The advantage of this traditional one-by-one visit mode is that only one kind of lesion is treated in one operation, the operation and anesthesia time is short, but the disadvantages include:

(1) there are treatment contradictions: strengthening antiplatelet is needed before PCI operation, which increases the risk of rupture of aortic dissection or ulcer and bleeding and even endangers life; in aortic endoluminal repair there is a concern about the risk of ischemia and even myocardial infarction due to untreated coronary heart disease.

(2) The patient is admitted to two wards in a hospital in sequence, and receives twice anesthesia, twice operations and twice perioperative treatment in sequence, which can lead to prolonged hospitalization time and increased hospitalization cost, increased risk and increased medical resource consumption.

We have begun exploring the field of pan-vascular disease, but there is no current literature on one-stop intraluminal interventional therapy for patients with aortic disease complicated by coronary heart disease.

The invention content is as follows:

the invention aims to provide the application of clopidogrel, ticagrelor, cilostazol, tirofiban, common heparin or bivalirudin in preparing a medicine for treating a pan-vascular disease.

For the above use, the dose of clopidogrel is 300 mg; or said ticagrelor dose is 180 mg, or said cilostazol dose is 100 mg.

In the application, the aspirin loading dose is 300mg, and the administration time is within 24 hours before operation; or the loading dose of the clopidogrel is 300mg, and the administration time is within 24 hours before operation.

In the application, the dose of aspirin is 100 mg/day/time, and the administration time is 1-30 days, or the dose of clopidogrel is 75 mg/day/time, and the administration time is 1-30 days.

For the above use, the clopidogrel, ticagrelor or cilostazol is enterally administered.

In the application, the enteral administration refers to that the medicine is ground and stirred uniformly by using water through a gastric tube which is pre-indwelling before an operation and then injected into the gastric intestine of a patient.

In the application, the tirofiban is intravenously administered, the administration dosage is (0.1-0.15) microgram per kilogram of body weight per minute, and the administration time is 1-24 hours; or the dosage of the heparin is 75-100 units/kg body weight; or for patients taking tirofiban together, the heparin dose is adjusted to 50-75 units/kg body weight; or the bivalirudin is administrated by the following method: intravenous injection of 0.75 mg/kg body weight, continuous intravenous drip of 1.75 mg/kg body weight.h.

For the above applications, the administration of heparin or bivalirudin requires monitoring of the clotting time of whole blood (ACT) and the ACT is maintained between 250 and 350 seconds during coronary intervention.

The application comprises the step of sequentially carrying out operations of aortic endoluminal repair and coronary interventional therapy on a patient in the application process.

The application comprises the steps of finishing the aortic intraluminal repair operation and finishing the coronary artery interventional therapy on the same platform.

In the application, the operation is completed in a single anesthesia process of a patient, and the anesthesia is general anesthesia or local anesthesia.

In the application, the aortic endoluminal repair is the placement of an aortic stent.

In the above application, the coronary artery interventional therapy adopts one or more of femoral artery, radial artery, brachial artery or ulnar artery as an access.

The application completes the complete suture of the femoral artery incision after the aortic intracavity repair, and the sheath catheter is inserted through the proximal end of the femoral artery incision by puncture under direct vision.

The above application, the sheath is selected from one or more of arterial sheaths with diameters of 6F, 7F and 8F.

The application is that the coronary artery interventional therapy is coronary artery stent implantation or percutaneous coronary artery sacculus forming operation.

After the coronary artery interventional therapy is completed, the femoral artery puncture point is sutured under direct vision, and the muscle layer and the cortex are sutured after sufficient hemostasis is achieved.

In the application, the femoral artery access path is surgically cut, and the puncture and the suture of the femoral artery are directly observed.

The above application, for patients with intraoperative contrast agent use in total amounts exceeding 2 ml/kg body weight, is post-operative hydrated.

In the application, 0.9% physiological saline is adopted for hydration, intravenous drip is carried out according to the rate of 0.5-1 ml/kg body weight, and the hydration time is 12-48 hours.

The application can be used for maintaining duplex antiplatelet therapy the next day after operation if no bleeding complications exist after operation.

In the above application, the aspirin dose is 75-100 mg/day, the clopidogrel dose is maintained for a long time or 75 mg/day, the ticagrelor dose is maintained for 6-12 months or 90 mg/time twice a day, the ticagrelor dose is maintained for 6-12 months or the cilostazol dose is 100 mg/time twice a day, the cilostazol dose is maintained for 6-12 months.

The invention aims to provide a one-stop operation method for combining coronary artery interventional therapy with aortic endoluminal repair, which sequentially carries out aortic endoluminal repair and coronary artery interventional therapy on a patient.

The operation method comprises the steps of finishing the aortic intraluminal repair operation and finishing the coronary artery interventional therapy on the same platform.

In the above operation method, the operation is completed in a single anesthesia process of the patient, and the anesthesia is general anesthesia or local anesthesia.

The above-mentioned operation method, the aortic endoluminal repair is the placement of an aortic stent.

The surgical method described above, wherein the procedure uses only the femoral artery as the access.

The operation method completes the complete suture of the femoral artery incision after the aortic intracavity repair, and the sheath catheter is inserted through the proximal end of the femoral artery incision by puncture under direct vision.

The above surgical method, wherein the sheath is selected from one or more of arterial sheaths with diameters of 6F, 7F and 8F.

The above-mentioned operation method, the coronary artery intervention treatment is coronary artery stent implantation or percutaneous coronary artery sacculus forming operation.

The above-mentioned operation method, the patient is administrated with aspirin or clopidogrel and the combination thereof before the operation.

In the above operation method, the dose of aspirin is 100 mg/day/time, and the administration time is 1 to 30 days, or the dose of clopidogrel is 75 mg/day/time, and the administration time is 1 to 30 days.

The operation method is characterized in that the aspirin loading dose is 300mg, and the administration time is 24 hours before the operation; or the loading dose of the clopidogrel is 300mg, and the administration time is within 24 hours before operation.

The above-mentioned surgical method, immediately before or during said coronary intervention, administering to the patient one or more of clopidogrel, ticagrelor, cilostazol, tirofiban, heparin or bivalirudin.

In the above surgical method, the dose of clopidogrel is 300 mg; or said ticagrelor dose is 180 mg, or said cilostazol dose is 100 mg.

In the above surgical method, the clopidogrel, ticagrelor or cilostazol is enterally administered.

In the above operation method, the enteral administration is performed by grinding the medicine through a gastric tube pre-indwelling before the operation, stirring the medicine with water, and injecting the mixture into the gastrointestinal tract of the patient.

In the above surgical method, the tirofiban is administered intravenously at a dose of (0.1 to 0.15) micrograms per kilogram of body weight per minute for a period of 1 to 24 hours; or the dosage of the heparin is 75-100 units/kg body weight; or for patients taking tirofiban together, the heparin dose is adjusted to 50-75 units/kg body weight; or the bivalirudin is administrated by the following method: intravenous injection of 0.75 mg/kg body weight, continuous intravenous drip of 1.75 mg/kg body weight.h.

In the above-described surgical method, the administration period of heparin or bivalirudin requires monitoring of the whole blood clotting time (ACT), and the ACT is maintained between 250 and 350 seconds in the coronary intervention.

After the coronary artery interventional therapy is completed, the femoral artery puncture point is sutured under direct vision, and the muscle layer and the cortex are sutured after sufficient hemostasis is achieved.

According to the operation method, the femoral artery access path is surgically cut, and the femoral artery is punctured and sutured under direct vision.

The above surgical method recommends postoperative hydration for patients whose intraoperative contrast medium is used in a total amount of more than 2 ml/kg body weight.

In the operation method, 0.9 percent of normal saline is adopted for hydration, intravenous drip is carried out according to the speed of 0.5-1 ml/kg body weight, and the hydration time is 12-48 hours.

The operation method can maintain duplex antiplatelet therapy the next day after operation if no bleeding complication exists after operation.

In the above operation method, the aspirin dose is 75-100 mg/day, the clopidogrel dose is maintained for a long time or 75 mg/day, the ticagrelor dose is maintained for 6-12 months or 90 mg/time twice a day, the ticagrelor dose is maintained for 6-12 months or the cilostazol dose is 100 mg/time, the cilostazol dose is maintained for 6-12 months twice a day.

Today, medical disciplines are becoming increasingly detailed and specialized, and we are increasingly realizing that patients are a whole. The understanding of the disease should be from the perspective of the patient, and if the same patient combines multiple diseases, we should cooperate with each other in multiple departments, evaluate comprehensively, strive to provide the individual and one-stop medical service for the patient, which is also the development trend of modern medical treatment.

For patients with aortic and coronary artery disease, we constructed a team of experts combined vascular surgery and cardiology, and have explored a one-stop procedure combining multiple cases of coronary intervention with a one-stop intra-aortic transluminal repair. The advantages of this one-stop treatment are:

(1) the two diseases are treated in a one-stop mode, so that the contradiction of antiplatelet treatment in the split operation is avoided, and the potential risk caused by the other disease in the split operation is also avoided;

(2) the patient can treat two diseases only by one anesthesia and one operation process, and the psychology is more acceptable;

(3) reduce the hospitalization cost, shorten the ICU time and the total hospitalization time, and reduce the medical resource consumption.

The difficulty with this one-stop treatment is:

(1) two department experts are required to form a composite technical team, and the requirements on the technical level and the coordination and coordination capability of the relevant disciplines of the hospital are high;

(2) the two diseases are treated synchronously, the total amount of the contrast agent used in a short time is increased, and adverse reactions related to the contrast agent are possibly increased;

(3) the perioperative period of coronary intervention requires dual antiplatelet therapy to reduce the risk of thrombus; the aorta intraluminal repair approach (such as femoral artery operation incision) is more prone to bleeding risks such as postoperative bleeding, subcutaneous ecchymosis, local hematoma, false aneurysm and the like.

Therefore, the connection of the two types of operation of aortic endoluminal repair and coronary intervention and the perioperative antithrombotic treatment become the key points. In order to solve the problem, a reasonable and feasible one-stop antithrombotic scheme which is a one-stop operation method combining coronary artery interventional therapy and aortic endoluminal repair is formulated. Meanwhile, the perioperative major hemorrhage is used as a main observation endpoint, and the safety of the one-stop treatment compared with the safety of the separate treatment in a one-stop operation method of the coronary artery interventional therapy and aortic endoluminal repair is compared.

Clinical trials for this project are in progress, and more than 10 cases of one-stop treatment of coronary artery interventional therapy combined with aortic endoluminal repair are completed at present, and the specific implementation method is shown in fig. 2.

The implementation of the invention has the following advantages: (1) the two diseases are treated in a one-stop mode, so that the contradiction of antiplatelet treatment in the fractional operation is avoided, and the potential risk of the fractional operation is also avoided; (2) the patient only undergoes one anesthesia and operation process, two diseases are treated, and the psychology is more acceptable; (3) reduce the hospitalization cost, shorten the total hospitalization time and reduce the medical resource consumption. (4) Has better long-term treatment effect on the 'pan-vascular disease'.

Drawings

FIG. 1, schematic representation of aorta and coronary arteries

FIG. 2, flow chart of clinical trial

Detailed Description

The following is an experimental illustration of a one-stop surgical approach in conjunction with coronary intervention combined with endovascular aortic repair, which is intended to illustrate the invention and not to limit it.

Experimental example 1

The patient was male, age 77, and diagnosed with coronary heart disease with aortic ulcer. Before operation, 100mg of aspirin is orally taken for 1 time/day for 5 consecutive days, the aorta endoluminal repair is firstly carried out by entering the right femoral artery under general anesthesia, and a stent is placed in the descending aorta; then the same patient is used for coronary artery radiography through the same access to prompt severe stenosis of the blunt edge branch, 300mg of clopidogrel is loaded through a gastric tube, then coronary artery interventional therapy is carried out, and a stent is placed in the blunt edge branch. The operation is smooth, the postoperative recovery is good, the major hemorrhage event does not occur, and the major hemorrhage, the acute myocardial infarction and other events do not occur in 1 year of follow-up visit.

Experimental example 2

Female, 72 years old, diagnosed with coronary heart disease with intraaortic hematoma. Before operation, 100mg of aspirin is orally taken for 1 time/day for 5 consecutive days. The aortic endoluminal repair is performed through the right femoral artery access under general anesthesia: one stent is placed in the descending aorta. Coronary angiography followed the same approach suggested 80% of anterior descending stenosis. Loading 300mg of clopidogrel through a gastric tube immediately, then carrying out coronary intervention treatment, and placing 1 stent in the anterior descending branch. The process is smooth. After the patient regularly takes aspirin and clopidogrel for antiplatelet treatment, events such as heavy bleeding and acute myocardial infarction do not occur, and events such as heavy bleeding and acute myocardial infarction do not occur in 1 year of follow-up visit.

Experimental example 3

The patient male, 62 years old, was diagnosed with coronary heart disease complicated by aortic dissection. Before operation, 100mg of aspirin is orally taken, 1 time/day of aspirin is continuously taken for 3 days, and aortic intraluminal repair is performed by entering a path through a right femoral artery under general anesthesia. Subsequently, 90% of anterior descending stenosis is prompted by coronary angiography when the coronary artery is accessed through the right radial artery, 300mg of clopidogrel is loaded through a gastric tube immediately, then coronary intervention treatment is carried out, and 1 stent is implanted in the anterior descending. The process is smooth. After the operation, aspirin and clopidogrel are regularly taken for anti-platelet treatment, and events such as heavy bleeding, acute myocardial infarction and the like do not occur.

Claims (22)

1. Application of clopidogrel, ticagrelor, cilostazol, tirofiban, common heparin or bivalirudin in preparing a medicament for treating pan-vascular diseases.

2. The use of claim 1, wherein the dose of clopidogrel is 300 mg; or said ticagrelor dose is 180 mg, or said cilostazol dose is 100 mg.

3. The use of claim 1, wherein the aspirin loading dose is 300mg administered within 24 hours prior to surgery; or the loading dose of the clopidogrel is 300mg, and the administration time is within 24 hours before operation.

4. The use of claim 1, wherein said aspirin is administered at a dose of 100 mg/day-times for a period of 1-30 days, or said clopidogrel is administered at a dose of 75 mg/day-times for a period of 1-30 days.

5. The use of any one of claims 1-4, wherein clopidogrel, ticagrelor or cilostazol is enterally administered.

6. The use of claim 5, wherein said enteral administration is via a pre-operatively pre-indwelling gastric tube, said medicament being ground and homogenized with water and then injected into the patient's gastrointestinal tract.

7. The use according to claim 1, wherein the tirofiban is administered intravenously at a dose of (0.1-0.15) micrograms per kilogram of body weight per minute for a period of 1-24 hours; or the dosage of the heparin is 75-100 units/kg body weight; or for patients taking tirofiban together, the heparin dose is adjusted to 50-75 units/kg body weight; or the bivalirudin is administrated by the following method: intravenous injection of 0.75 mg/kg body weight, continuous intravenous drip of 1.75 mg/kg body weight.h.

8. The use of any one of claims 1 to 7 wherein the administration of heparin or bivalirudin requires monitoring of the whole blood clotting time (ACT) to maintain ACT between 250 and 350 seconds during coronary intervention.

9. Use according to claims 1-8, wherein the patient is subjected to an aortic endoluminal prosthesis and a coronary intervention in sequence during the application.

10. Use according to claim 9, wherein the endovascular aortic repair is performed first and the coronary intervention is performed in the same stage.

11. The use of claim 9, wherein the procedure is performed during a single anesthetic procedure on the patient, the anesthetic being general or local.

12. The use according to any one of claims 9-11, wherein the aortic endoluminal repair is the placement of an aortic stent.

13. The use of any of claims 9-12, wherein the coronary intervention procedure uses one or more of a femoral artery, a radial artery, a brachial artery, or an ulnar artery as an access route.

14. The use of claim 13, wherein the femoral incision is completely sutured after the aortic endoluminal repair is completed and the sheath is reinserted through the proximal end of the femoral incision under direct visualization.

15. The use of claim 14, wherein the sheath is selected from one or more of 6F, 7F, 8F diameter arterial sheaths.

16. Use according to any one of claims 9-12, wherein the coronary intervention is a coronary stent implantation or a percutaneous coronary balloon angioplasty.

17. The use according to any one of claims 9 to 16, wherein the femoral artery puncture site is sutured under direct visualization after the coronary intervention is completed, and the muscular and cortical layers are sutured after sufficient hemostasis.

18. The use of any one of claims 9-16, wherein the femoral access is surgically opened, and the femoral artery is punctured and sutured under direct visualization.

19. Use according to any of claims 9-18, wherein the post-operative hydration is performed on a patient whose total amount of contrast agent used during the operation exceeds 2 ml/kg body weight.

20. The use of claim 19, wherein the hydration is performed by intravenous drip using 0.9% physiological saline at a rate of 0.5-1 ml/kg body weight for a period of 12-48 hours.

21. The use according to any one of claims 9 to 20, wherein dual antiplatelet therapy is initiated the next day after surgery without bleeding complications.

22. The use according to any one of claims 9 to 20, wherein said aspirin dose is 75 to 100 mg/day, long-term maintenance or said clopidogrel dose is 75 mg/day, maintenance is 6 to 12 months or said ticagrelor dose is 90 mg/time, twice daily, maintenance is 6 to 12 months or said cilostazol dose is 100 mg/time, twice daily, maintenance is 6 to 12 months.

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