Tailoring Bleeding Reduction Approaches in Patients Undergoing PCI

Phase 4

Recruiting

• Conditions: Coronary Artery Disease
• Interventions: Drug: aspirin plus clopidogrel; Drug: prasugrel or ticagrelor

• Registration Number: NCT05681702
• Lead Sponsor: University of Florida

Brief Summary

Two strategies have both proven to be effective in reducing bleeding complications while preserving efficacy compared with maintaining long-term DAPT with aspirin and a potent P2Y12 inhibitor: a) DAPT de-escalation (i.e., switching from prasugrel or ticagrelor to clopidogrel while maintaining aspirin) and b) potent P2Y12 inhibitor monotherapy (i.e., maintaining prasugrel or ticagrelor and dropping aspirin). These strategies have been tested in a number of trials and have led to changes in practice guidelines to consider either one of these strategies as bleeding reduction approaches among ACS patients undergoing PCI. However, comparative assessments between DAPT de-escalation and potent P2Y12 inhibitor monotherapy are lacking.

Detailed Description

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor represents the standard of care for the prevention of atherothrombotic events in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). In particular, in ACS patients undergoing PCI, DAPT is initiated during the index event and maintained for up to 12 months to prevent stent-related complications as well as ischemic recurrences in non-treated coronary segments. Three oral P2Y12 inhibitors are currently recommended in this setting: clopidogrel, prasugrel, and ticagrelor. However, in ACS patients undergoing PCI, prasugrel and ticagrelor are preferred over clopidogrel based on results of large-scale clinical trials showing their superior reduction in ischemic events, including stent thrombosis. Nevertheless, such ischemic benefit occurs at the expense of increased bleeding. These observations are attributed to the greater antiplatelet potency of prasugrel and ticagrelor over clopidogrel. Importantly, accruing evidence support that bleeding complications carry significant prognostic implications, including increased mortality, underscoring the need to define antiplatelet strategies associated with reduced bleeding while preserving ischemic efficacy. The notion that most recurrent ischemic events, including stent thrombosis, occur early after the index event (i.e., 1-3 months post PCI) has prompted the design of clinical trials assessing antiplatelet treatment regimens consisting in the use of agents with enhanced platelet inhibition during the first months after PCI followed by approaches with reduced platelet inhibition. To this extent, two strategies have both proven to be effective in reducing bleeding complications while preserving efficacy compared with maintaining long-term DAPT with aspirin and a potent P2Y12 inhibitor: a) DAPT de-escalation (i.e., switching from prasugrel or ticagrelor to clopidogrel while maintaining aspirin) and b) potent P2Y12 inhibitor monotherapy (i.e., maintaining prasugrel or ticagrelor and dropping aspirin). These strategies have been tested in a number of trials and have led to changes in practice guidelines to consider either one of these strategies as bleeding reduction approaches among ACS patients undergoing PCI. However, comparative assessments between DAPT de-escalation and potent P2Y12 inhibitor monotherapy are lacking.

Study Timeline

• Study First Submitted: 2023-01-04
• Study First Submitted QC: 2023-01-04
• Study First Posted: 2023-01-12
• Study Start: 2023-02-15
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-30
• Last Update Posted: 2025-02-03
• Primary Completion: 2025-07-31
• Study Completion: 2025-12-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Patients who presented with chronic coronary syndrome, underwent PCI and have been on maintenance treatment with DAPT, composed of low-dose aspirin (81mg od) and prasugrel (10 mg od) or ticagrelor (90 mg bid) for at least 30 days. Or patients that presented with an Acute coronary syndrome (ACS) event and underwent PCI and have been on maintenance treatment with DAPT, composed of low-dose aspirin (81mg od) and prasugrel (10mg od) or ticagrelor (90mg bid) for 3 months or greater.
2. Age ≥18 years old
3. Provide written informed consent

Exclusion Criteria

1. Prior history of stent thrombosis
2. On treatment with any oral anticoagulant (vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban) or chronic low-molecular-weight heparin (at venous thrombosis treatment, not for prophylaxis)
3. Renal failure requiring dialysis
4. Patients with known bleeding diathesis or coagulation disorders
5. Known severe hepatic impairment
6. Hemodynamic instability
7. Hypersensitivity to clopidogrel
8. Pregnant and breastfeeding women [women of childbearing age must use reliable birth control (i.e., oral contraceptives) while participating in the study]

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DAPT de-escalation	aspirin plus clopidogrel	Aspirin 81-mg od and clopidogrel 75-mg qd.
Potent P2Y12 monotherapy	prasugrel or ticagrelor	Potent P2Y12 inhibitor with prasugrel 10 mg od or ticagrelor 90 mg BID.

Primary Outcome Measures

Name	Time	Method
Thrombus formation defined as AUC measured by T-TAS	30 days	Comparison of the area under the curve (AUC) determined by Total Thrombus formation Analysis System (T-TAS) between potent P2Y12 monotherapy strategy and de-escalation strategy (trough effect).

Trial Locations

Locations (1)

University of Florida; 🇺🇸 Jacksonville, Florida, United States