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coronary bypass transplant patients with diabetes combined with diabetic coronary artery bypass transplantation 1 year clinical observation of low-dose ticagrelor
Clinical observation of low dose ticagrelor in cornary artery bypass grafting patients combined with diabetes
Pan Yanpeng Chen Gang Liu Xu
Author unit: 450016 Zhengzhou Seventh People's Hospital Zhengzhou Cardiovascular Disease Hospital, Southern Medical University, Department of Cardiovascular Surgery, Henan Cardiovascular Disease Hospital, Affiliated to Southern Medical University,
, Correspondence Author: Pan Yanpeng, Email: [email protected]
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Target
Target
Consolidated diabetes The clinical results of low-dose ticagrelor in patients with coronary artery bypass transplantation (CABG) for 1 year after surgery provide a theoretical basis for optimizing antiplatelet therapy.
method
was successively included in , , Zhengzhou Seventh People's Hospital, 6235 CABG patients with diabetes, and were given orally ticagrelor 60 mg twice/d combined with aspirin 100 mg/d dual-tether after surgery. Antiplatelet therapy. The main study endpoints were the incidence of major adverse cardiovascular events (MACCE), including myocardial infarction, stroke, / transient cerebral ischemia attacks, and cardiogenic death; the main safety endpoint was severe bleeding, and the secondary safety was The end point is secondary or mild bleeding.
Results
average follow-up time (14.0±1.5) months, 16 (6.8%) patients had MACCE, 3 of which were centrigenic deaths (1.3%), 7 of myocardial infarction (3.0%), stroke/transient There were 6 cases of cerebral ischemia attacks (2.6%). Primary safety endpoints: no severe bleeding occurred, 12 cases of secondary bleeding (5.1%), and 37 cases of mild bleeding (15.7%). 22 cases (9.4%) experienced drug-related dyspnea, and 4 cases (1.7%) stopped the medication due to dyspnea.
Conclusion
combined with diabetic patients with CABG after surgery used low-dose ticagrelor combined with aspirin dual antiplatelet therapy showed good safety and tolerability.
01 Research Design
This study is a real-world prospective study. Patients with diabetes who were continuously included in the CABG patients treated with diabetes at the Seventh People's Hospital of Zhengzhou City from January 2018 to December 2019. After surgery, they were given orally ticagrelor 60 mg 2 times/d combined with aspirin 100 mg/d dual antiplatelet therapy. , other treatments include beta blockers, statins, angiotensin converting enzyme inhibitors/angiotensin II receptor antagonists, etc.
02 Case inclusion and exclusion criteria
Inclusion criteria: (1) Age 18-80 years old; (2) coronary artery single or multiple lesions undergo CABG surgery; (3) Diabetes that require drug treatment; (4) Signed Informed consent form.
exclusion criteria: (1) Those who underwent other cardiac surgery or emergency CABG at the same time; (2) Other anticoagulant or antithrombotic drugs are required after the operation; (3) Severe bleeding tendency; (4) Severe organ insufficiency insufficiency in the organs; (2) or immunologic deficits; (5) Use of moderate and severe inhibitors of CYP3A; (6) Women with poor compliance, pregnancy or breastfeeding.
This study has been approved by the Ethics Committee of Zhengzhou Seventh People's Hospital (ethical batch number: IEC-C-007-A09-V1.0), and all patients signed an informed consent form.
03 Follow-up endpoint
The main endpoint is the incidence of major adverse cardiac and cerebrovascular events (MACCE), including myocardial infarction, stroke/transient ischemic attacks and cardiac progenitor Death; the primary safety endpoint is Severe bleeding, the secondary safety endpoint is secondary or mild bleeding.
Myocardial infarction follows the general definition of myocardial infarction formulated by Thygesen et al. [4]. Stroke is defined as acute neurological dysfunction caused by central nervous system vascular causes and is clearly diagnosed by imaging (CT/MR). Transient ischemic attacks are temporary neurological dysfunction caused by focal cerebral ischemia, spinal cord ischemia or retinal ischemia, and there is no acute cerebral infarction of [5]. Cardiac death includes cardiac arrest , often accompanied by symptoms of myocardial ischemia , accompanied by new ST segment elevation or new left bundle branch block, and (or) coronary angiography and (or) The autopsy showed thrombosis [5].Severe bleeding is defined as intracranial hemorrhage, or significant hemorrhaglobin reduction of more than 50 g/L, or fatal bleeding (a bleeding event that directly leads to death within 7 days). Secondary bleeding was observable bleeding that did not require treatment, with a decrease of 30-50 g/L of hemoglobin, and mild bleeding was a significant bleeding event that did not meet the severe and secondary criteria [6].
was followed up through outpatient clinic, telephone, and letters. All patients were followed up after surgery, with an average follow-up (14.0±1.5) months.
04 Statistical description
Use SPSS 20.0 software for data processing. The measurement data of the normal distribution of is represented by M±SD, and the count data is represented by percentage composition ratio.
01 Basic preoperative situation of patients
35 CABG patients with diabetes were included in this study. The clinical characteristics and medication status are shown in Table 1, with an age of 32 to 78 years old, an average of (54.3±5.8) years old, and 82 females (34. 9%) , the mean left ventricular ejaculation fraction was 52.3%±6.2%. During the follow-up period, the patient received other CABG secondary prevention drugs: aspirin 100%, angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist 62.6%, β receptor blocker 75.3%, and statin Drug-like 97.0%.Table 1 Preoperative baseline data of CABG patients with diabetes and other secondary prevention medications during postoperative follow-up
02 Study endpoint
mean follow-up (14.0±1.5) months, 16 cases (6.8 %) MACCE event occurred, the center There were 3 cases of primary deaths (1.3%), 7 cases (3.0%) with new myocardial infarctions, and 6 cases (2.6%) with stroke/transient ischemic attacks. Primary safety endpoints: no serious bleeding occurred; 12 cases of secondary bleeding (5.1%) and 37 cases of mild bleeding (15.7%). Twenty-two (9.4%) patients had drug-related dyspnea, and four (1.7%) stopped the drug due to dyspnea. See Table 2.
Table 2 Study endpoint situation [Case (%)]
Note: MACCE: Major adverse cerebrovascular events
Discussion
occlusion rate of axle blood vessels after CABG surgery for 1 year is about 10%~20%[7], secondary CABG Among the patients, 80% were [8] caused by bridge vascular occlusion. The reasons are thrombosis and secondary bridge vascular endothelial hyperplasia. Therefore, effective antiplatelet therapy can improve bridge vascular patency to a certain extent. Currently, the dual antiplatelet strategy adopted for patients after CABG surgery is aspirin + clopidogrel /ticagrelor, while diabetic patients have impaired response to clopidogrel. Even if the dosage of clopidogrel is increased, the postoperative The incidence of adverse events is still relatively high [9]. Therefore, for CABG patients with diabetes, aspirin + ticagrelor dual antiplatelet regimen [10] is more preferred. Compared with clopidogrel, ticagrelor can inhibit platelet function faster, stronger and more consistently platelet function [11]. PLATO-CABG subgroup study showed that aspirin + ticagrelor significantly reduced the risk of all-cause death and cardiovascular death after CABG surgery [12]; a DACAB study for Chinese people showed that ticag A dual antiplatelet regimen of 90 mg 2 times/d combined with aspirin can significantly improve the vascular patency rate of saphenous vein bridge in ACS patients 1 year after CABG. Compared with the Caucasian population, the conventional dose of ticagrelor 90 mg 2 times/d has a higher incidence of adverse reactions such as bleeding, dyspnea and other adverse reactions in Asian populations [13-15]. The literature reported that 0.9% of patients discontinued [16], while in a real-world study, the proportion was as high as 11.6% [17]. PLATO study also showed that the incidence of ticagrelor dyspnea increased [18]. PEGASUS-TIMI 54[17] is a double-blind multicenter clinical trial. 21,162 patients with previous history of myocardial infarction received ticagrelor 90 mg twice/d, 60 mg twice/d or comfort. The incidence of MACCE in the two different doses of ticagrelor group was significantly lower than that in the placebo group (Ticagrelor 90 mg group: HR=0.85, 95% CI: 0.75~0.96, P=0.008; Relo 60 mg group: HR=0.84, 95% CI: 0.74~0.95, P=0.004), and the low-dose ticagrelor group showed a better risk/benefit ratio. Compared with the Caucasian population, the bioavailability of ticagrelor in the Asian population has significantly increased [3].Therefore, whether it can reduce the occurrence of adverse reactions by reducing the dose of ticagrelor while achieving satisfactory platelet inhibition effects has become a hot topic in domestic clinical research in recent years [19-21]. Li et al. [3] Through a study of taking low doses (45 mg 2 times/d) or conventional doses (90 mg 2 times/d) of healthy Chinese people, the same anti-anti-anti-anti-anti-anti-anti-anti-anti-anti-anti-d) patients. Platelet effect, and adverse reactions such as bleeding and dyspnea are even lower in the low-dose group. Hiasa et al. [22] reported that for Asian patients with percutaneous coronary intervention or acute coronary syndrome for more than 3 months, the inhibition of platelet aggregation was taken ticagrelor 45 mg twice/d. It was slightly lower than 90 mg 2 times/d dose group, but still higher than the clopidogrel group.
In this study, for patients with CABG with diabetes, aspirin 100 mg/d combined with ticagrelor 60 mg twice/d oral dual antiplatelet therapy was used after surgery. After 1 year of follow-up, the incidence of MACCE was shown to be 6.8%, of which there were 1.3% of centrogenic deaths, 3.0% of new myocardial infarctions, and 2.6% of stroke/transient ischemic attacks. The incidence of MACCE in DACAB study [1]. In terms of the main safety endpoints of
, there were 49 cases of secondary and mild bleeding, and no serious bleeding occurred, indicating that ticagrelor 60 mg 2 times/d has good safety for CABG patients with diabetes. Previous reports have been reported that ticagrelor's advantages in reducing the occurrence of ischemic events may disappear due to the increase in bleeding events [23]. But our study shows that severe bleeding events occur rarely in real-world studies. Dayu's study [24] also showed that the incidence of major bleeding in ticagrelor in Chinese population was low, with the incidence of major bleeding events within one year 1.3%, which was lower than that of the PLATO study.
Among the 235 patients in this group, 22 experienced drug-related dyspnea, with an incidence rate of 9.4%, slightly lower than that of the PLATO study (14.5%) and PEGASUS-TIMI 54 (15.84%), of which 4 (1.7%) were severe due to severe cases (1.7%). Difficulty in breathing leads to stopping medication. Dyspnea is the most common adverse reaction of ticagrelor [25], showing a dose-dependent [26], and its related antagonist is currently lacking in clinical practice. The application of theophylline to the adenosine inhibitor on ticagrelor is still lacking clinical evidence [27]; TROCADERO trial [28] aims to study whether caffeine can not affect ticagrelor Antiplatelet aggregation relieves dyspnea caused by ticagrelor, but no clear conclusion has been drawn. Currently, effective and mature methods for treating dyspnea caused by ticagrelor are still lacking in clinical practice.
Limitations of this study: The design of descriptive study limits our conclusions, the samples are from single centers and the sample size is small; descriptive studies may have certain bias in the collection and interpretation of data, etc. However, in real-world studies, CABG patients with diabetes combined with diabetes showed good safety and tolerance after surgery. The proportion of drug discontinuation caused by severe adverse reactions was 1.7% , no serious bleeding incidents occurred during the follow-up period. However, multiple center, large samples of randomized controlled studies and long-term follow-up are still needed to further observe their clinical effectiveness.
Reference
Source of this article
Pan Yanpeng, Chen Gang, Liu Xu. One-year clinical observation on the use of low-dose ticagrelor after surgery in patients with coronary artery bypass transplantation with diabetes [J]. Chinese Journal of Cardiovascular, 2022, 27( 3): 269-272. DOI: 10.3969/j.issn.1007-5410.2022.03.013.
