Effect of ticagrelor versus clopidogrel plus aspirin in aging patients with unstable angina after elective percutaneous coronary intervention

Plain English Summary

Background and study aims
The incidence of non-ST-elevation acute coronary syndrome (NSTE-ACS) is increasing year by year. At present, the most effective treatment for NSTE-ACS is percutaneous coronary intervention (PCI). However, due to various clinical conditions (such as diabetes and dyslipidemia) or complications related to coronary vascular disease (such as complex coronary artery disease and unstable plaques) the risk of ischemic events remains high after PCI. Antiplatelet aggregation therapy has become the focus of current treatment following PCI. For NSTE-ACS patients undergoing PCI postoperative antiplatelet therapy, the current guidelines recommend dual antiplatelet therapy (DAPT) for at least 12 months. However, NSTE-ACS ischemic or bleeding events after PCI are more frequent in elderly patients than in normal patients, and while dual antiplatelet therapy reduces the risk of ischemia, it also increases bleeding. Patients with unstable angina pectoris (UAP) fall into the ACS category but have a relatively low risk of ischemia compared to NSTEMI, so it is still difficult to optimize the post-PCI antiplatelet regimen of elderly UAP patients. The latest guidelines suggest that clopidogrel can be used instead of ticagrelor in patients with high bleeding risk or other contraindications. A number of studies have shown that in patients receiving DAPT, the value of stopping aspirin 3–6 months after stent implantation depends on a balance between ischemia and bleeding risk. If DAPT is discontinued 3 or 6 months after PCI, there is an increased risk of stent thrombosis and myocardial infarction. Although such short-term DAPT is associated with an increased risk of myocardial infarction (heart attack) and stent thrombosis (blood clotting) after PCI, long-term DAPT increases the risk of bleeding, thus offsetting its advantage for reducing recurrent ischemic events. Therefore, whether long- or short-term DAPT followed by aspirin or other treatments such as P2Y12 inhibitor monotherapy are used after PCI, the results are not completely satisfactory for elderly UAP patients.
In order to reduce the risk of bleeding while not increasing the incidence of ischemic events, a recent study proposed changing the duration of dual antiplatelet therapy without increasing the incidence of ischemic events. Ticagrelor may increase the risk of bleeding in elderly NSTE-ACS patients, but is more effective than clopidogrel in reducing ischemic events. However, the above study is aimed at patients with high ischemic risk. The antiplatelet regimen of elderly UAP patients who have both low ischemic risk and high bleeding risk is unclear. Therefore, the aim of this study is to compare bleeding events and the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) between short-term (ticagrelor 90 mg bid (twice daily) + aspirin 100 mg qd (once daily)) and long-term (clopidogrel 75 mg qd + aspirin 100 mg qd) DAPT after elective PCI in elderly patients with UAP.

Who can participate?
Adults aged older than 65 years with unstable angina pectoris who successfully underwent a elective PCI operation with no complications during the perioperative period.

What does the study involve?
The patients successfully complete the PCI procedure, which is performed in accordance with current guidelines, during the period of hospitalization. Heparin is used during the procedure for an activated clotting time >250 seconds. If the procedure lasts more than an hour, an additional 2,000 IU of heparin is administered. Before admission, all patients are advised to take aspirin (300 mg) and clopidogrel (300 mg) / ticagrelor (180 mg) at least 2 hours before the PCI.
The patients are divided according to preprocedural antiplatelet therapy into two groups, a ticagrelor group and a clopidogrel group after PCI. In the ticagrelor group, patients are first treated with ticagrelor 90 mg bid and aspirin 100 mg qd for up to 3 months unless there is major bleeding or MACCE, then aspirin is discontinued during the remainder of the 12-month course of treatment. The clopidogrel group receive clopidogrel 75 mg qd and aspirin 100 mg qd for the entire 12 months. Patients who also present with hypertension, diabetes or other diseases continue to receive treatment.
At 1, 3 and 6 months after treatment, all patients are followed up by telephone, outpatient service and hospitalization. Laboratory examinations, electrocardiography, and coronary artery CT or angiography are performed at 12 months after the procedure.

What are the possible benefits and risks of participating?
There is no significant benefit to those involved in the study. They will have the opportunity to learn about research in this field. This information may ultimately be important in the long run to help develop more effective antiplatelet regimens, especially for elderly patients with unstable angina pectoris. Because being older is a high-risk factor for bleeding and ischemia, the current NSTE-ACS guidelines recommend aspirin combined with ticagrelor for 12 months after PCI. Nevertheless, UAP compared with the low risk of NSTEMI ischemia, all routine dual antiplatelet therapy may not benefit from reducing the risk of ischemia. Conversely, for elderly patients, long-term DAPT treatment may increase the risk of bleeding. This study, in order to compare two different antiplatelet regimens, provides valuable experience for the future treatment of elderly UAP patients after PCI. Elderly patients have a high relative risk of bleeding. The 2020 ESC guidelines point out that NSTE-ACS patients with high bleeding risk can be downgraded or reduced dual antiplatelet term, and the treatment options do not pose a risk to the subjects.

Where is the study run from?
Taicang Hospital affiliated to Suzhou University (Taicang First People's Hospital) (China)

When is the study starting and how long is t expected to run for?
February 2018 to March 2021

Who is funding the study?
Science and Technology Program of Taicang City (China)

Who is the main contact?
Dr Dayang Chai
dayangchai@outlook.com

Contact information

Dr Dayang Chai
Scientific

Department of Cardiology
Taicang City First People's Hospital
Taicang
215400
China

ORCID ID	0000-0002-3389-5555
Phone	+86 (0)18625111325
Email	dayangchai@outlook.com

Study information

Eligibility

Locations

Countries of recruitment

• China

Study participating centre

Sponsor information

Funders

Funder type

Government

Results and Publications

Study outputs

Additional files

ISRCTN13088814_PROTOCOL.docx

uploaded 04/05/2021

ISRCTN13088814_BasicResults_06May21.pdf

Uploaded 06/05/2021

ISRCTN13088814_BasicResults_18June21.pdf

Uploaded 18/06/2021

Editorial Notes

18/06/2021: The following changes have been made:
1. The basic results of this trial have been updated and uploaded as an additional file.
2. The total final enrolment number has been changed from 178 to 196.
06/05/2021: The basic results of this trial have been uploaded as an additional file. The intention to publish date was changed from 01/05/2021 to 01/03/2022.
04/05/2021: Uploaded protocol (not peer-reviewed) as an additional file. Version n/a, no date.
06/04/2021: Trial's existence confirmed by the Institutional Ethics Committee of Taicang First People's Hospital.